Moorestown, New Jersey, United States
biotecHOPE™ 2023
biotecHOPE™ 2023
DAYBUE™ (trofinetide)
DAYBUE™ (trofinetide)
DAYBUE™ (trofinetide)
DAYBUE™ (trofinetide)
DAYBUE™ (trofinetide)
March 10, 2023
General
Acadia Pharmaceuticals Announces U.S. FDA Approval of DAYBUE™ (trofinetide) for the Treatment of Rett Syndrome in Adult and Pediatric Patients Two Years of Age and Older
— First and only approved therapy for Rett syndrome, a rare, neurodevelopmental disorder, which affects 6,000 to 9,000 patients in the U.S.1
— Company expects DAYBUE to be available by the end of April, 2023
— Rare Pediatric Disease Priority Review Voucher granted in connection with approval
— Conference call and webcast to be held March 13, 2023 at 8:30 a.m. Eastern Time
SAN DIEGO–(BUSINESS WIRE)–Mar. 10, 2023– Acadia Pharmaceuticals Inc. (Nasdaq: ACAD) today announced that the U.S. Food and Drug Administration (FDA) has approved DAYBUE™ (trofinetide) for the treatment of Rett syndrome in adult and pediatric patients two years of age and older. DAYBUE is the first and only drug approved for the treatment of Rett syndrome.
This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20230303005382/en/
(Graphic: Business Wire)
“Today marks an important milestone for the Rett community and Acadia. As the first FDA-approved drug for the treatment of Rett syndrome, DAYBUE now offers the potential to make meaningful differences in the lives of patients and their families who have lacked options to treat the diverse and debilitating array of symptoms caused by Rett syndrome,” said Steve Davis, Acadia’s Chief Executive Officer. “We are grateful to all of the Rett syndrome patients, caregivers, clinical investigators and our employees who have contributed to making today a reality and look forward to getting DAYBUE to patients as quickly as possible.”
“Rett syndrome is a profoundly debilitating and complex, rare, neurodevelopmental disorder that presents differently across patients and can lead to an array of unpredictable symptoms throughout the course of a patient’s life,” said Jeffrey L. Neul, M.D., Ph.D., Annette Schaffer Eskind Chair and Director, Vanderbilt Kennedy Center, Professor of Pediatrics, Division of Neurology, Pharmacology, and Special Education, Vanderbilt University Medical Center and Phase 3 LAVENDER™ study investigator. “Now, for the first time after decades of clinical research, healthcare providers finally have a treatment option to address a range of core behavioral, communication and physical symptoms for their patients living with Rett syndrome.”
Rett syndrome is a complex, rare, neurodevelopmental disorder typically caused by a genetic mutation on the MECP2 gene.2,3 It is characterized by a period of normal development until six to 18 months of age, followed by significant developmental regression with loss of acquired communication skills and purposeful hand use.4 Symptoms of Rett syndrome may also include development of hand stereotypies, such as hand wringing and clapping, and gait abnormalities.5 Rett syndrome is believed to affect 6,000 to 9,000 patients in the U.S., with a diagnosed population of approximately 4,500 U.S. patients.1,6
The FDA approval of DAYBUE was supported by results from the pivotal Phase 3 LAVENDER study evaluating the efficacy and safety of trofinetide versus placebo in 187 female patients with Rett syndrome five to 20 years of age. In the study, treatment with DAYBUE demonstrated statistically significant improvement compared to placebo on both co-primary efficacy endpoints, as measured by the change from baseline in Rett Syndrome Behaviour Questionnaire (RSBQ) total score (p=0.018) and the Clinical Global Impression-Improvement (CGI-I) scale score (p=0.003) at week 12. The RSBQ is a caregiver assessment that evaluates a range of symptoms of Rett syndrome including vocalizations, facial expressions, eye gaze, hand movements (or stereotypies), repetitive behaviors, breathing, night-time behaviors and mood. The CGI-I is a global physician assessment of whether a patient has improved or worsened. In the study, the most common side effects were diarrhea (82%) and vomiting (29%).
“This is a historic day for the Rett syndrome community and a meaningful moment for the patients and caregivers who have eagerly awaited the arrival of an approved treatment for this condition,” said Melissa Kennedy, Chief Executive Officer of the International Rett Syndrome Foundation. “Rett syndrome is a complicated, devastating disease that affects not only the individual patient, but whole families. With today’s FDA decision, those impacted by Rett have a promising new treatment option that has demonstrated benefit across a variety of Rett symptoms, including those that impact the daily lives of those living with Rett and their loved ones.”
DAYBUE is expected to be available in the U.S. by the end of April, 2023.
In 2018, Acadia entered into an exclusive license agreement with Neuren Pharmaceuticals Limited (ASX: NEU) for the development and commercialization of trofinetide for the treatment of Rett syndrome and other indications in North America.
With the FDA approval of DAYBUE, Acadia has received a Rare Pediatric Disease Priority Review Voucher, which can be used to obtain priority review for a subsequent application.
Acadia Connect® Offers Dedicated Patient and Family Support and Resources
Acadia Connect® is a multi-faceted support program that will offer personal assistance, financial resources and prescription support to patients and caregivers starting and continuing appropriate DAYBUE therapy. Each dedicated support team includes a nurse care coordinator, a family access manager and 24/7 clinical pharmacist support. For more information, visit AcadiaConnect.com or call 1-844-737-2223, Monday to Friday, 8 a.m. to 8 p.m. Eastern Time.
Please read the accompanying full Prescribing Information, also available at DAYBUE.com
About Rett Syndrome
Rett syndrome is a rare, complex, neurodevelopmental disorder that may occur over four stages and affects approximately 6,000 to 9,000 patients in the U.S., with approximately 4,500 patients currently diagnosed according to an analysis of healthcare claims data.1,2,4,6 A child with Rett syndrome exhibits an early period of apparently normal development until six to 18 months, when their skills seem to slow down or stagnate. This is typically followed by a duration of regression when the child loses acquired communication skills and purposeful hand use. The child may then experience a plateau period in which they show mild recovery in cognitive interests, but body movements remain severely diminished. As they age, those living with Rett may continue to experience a stage of motor deterioration which can last the rest of the patient’s life.4 Rett syndrome is typically caused by a genetic mutation on the MECP2 gene.3 In preclinical studies, deficiency in MeCP2 function has been shown to lead to impairment in synaptic communication, and the deficits in synaptic function may be associated with Rett manifestations.3,7,8
Symptoms of Rett syndrome may also include development of hand stereotypies, such as hand wringing and clapping, and gait abnormalities.5 Most Rett patients typically live into adulthood and require round-the-clock care.2,9
About DAYBUE ™ (trofinetide)
Trofinetide is a synthetic version of a naturally occurring molecule known as the tripeptide glycine-proline-glutamate (GPE). The mechanism by which trofinetide exerts therapeutic effects in patients with Rett syndrome is unknown. In animal studies, trofinetide has been shown to increase branching of dendrites and synaptic plasticity signals.10,11
About Acadia Pharmaceuticals
Acadia is advancing breakthroughs in neuroscience to elevate life. For almost 30 years we have been working at the forefront of healthcare to bring vital solutions to people who need them most. We developed and commercialized the first and only approved therapies for hallucinations and delusions associated with Parkinson’s disease psychosis and for the treatment of Rett syndrome. Our clinical-stage development efforts are focused on treating the negative symptoms of schizophrenia, Alzheimer’s disease psychosis and neuropsychiatric symptoms in central nervous system disorders. For more information, visit us at www.acadia.com and follow us on LinkedIn and Twitter.
View source version on businesswire.com: https://www.businesswire.com/news/home/20230303005382/en/
Acadia wins FDA nod for Rett syndrome therapy
Mar. 10, 2023 10:20 PM ET
ACADIA Pharmaceuticals Inc. (ACAD), NURPF
By: Dulan Lokuwithana, SA News Editor
Acadia Pharmaceuticals (NASDAQ:ACAD) announced late Friday that the FDA greenlighted trofinetide under the brand name Daybue to treat the rare genetic neurodevelopmental disorder Rett syndrome in those aged two years and older.
https://seekingalpha.com/news/3946547-acadia-wins-fda-nod-for-rett-syndrome-therapy
Eplontersen
DAYBUE™ (trofinetide)
Eplontersen
Ionis announces FDA acceptance of New Drug Application for eplontersen for the treatment of hereditary transthyretin-mediated amyloid polyneuropathy (ATTRv-PN)
March 7, 2023 at 7:05 AM EST
- 35-week data included in the filing demonstrated a statistically significant and clinically meaningful change from baseline for co-primary and secondary endpoints compared to external placebo group
- Eplontersen previously granted Orphan Drug Designation for transthyretin-mediated amyloidosis
- FDA assigns PDUFA action date of Dec. 22, 2023
CARLSBAD, Calif., March 7, 2023 /PRNewswire/ -- Ionis Pharmaceuticals (Nasdaq: IONS) today announced that the U.S. Food and Drug Administration (FDA) has accepted for review a New Drug Application (NDA) for eplontersen, an investigational antisense medicine for the treatment of people living with hereditary transthyretin-mediated amyloid polyneuropathy (ATTRv-PN). The application has been given a Prescription Drug User Fee Act (PDUFA) action date of Dec. 22, 2023.
In its acceptance letter, the FDA stated that it has not identified any review issues and did not make any additional data requests. The FDA also noted that it is not planning to hold an advisory committee meeting to discuss the application.
Patients with ATTRv-PN experience ongoing debilitating nerve damage throughout their body resulting in the progressive loss of motor function. These patients accumulate TTR in other major organs, which progressively compromises their function and eventually leads to death within five to fifteen years of disease onset.
"We are excited by today's FDA acceptance of our NDA filing as it brings Ionis and our partner, AstraZeneca, one step closer to making eplontersen available to patients with ATTR polyneuropathy," said Eugene Schneider, M.D., executive vice president and chief clinical development officer at Ionis. "Significant reductions in TTR protein levels were observed during the NEURO-TTRansform 35-week interim analysis. Overall, the interim analysis demonstrated eplontersen has the potential to make a positive impact on disease progression and improve quality of life in a substantial number of patients."
The NDA is based on results from the global Phase 3 NEURO-TTRansform study presented at the International Symposium on Amyloidosis (ISA). In the 35-week interim analysis, eplontersen demonstrated a statistically significant and clinically meaningful change from baseline for its co-primary and key secondary endpoints compared to the external placebo group. In the study, eplontersen achieved a significant mean reduction (p<0.0001) in the co-primary endpoint of serum transthyretin (TTR) concentration compared to baseline. Eplontersen also demonstrated a significant treatment effect on the co-primary endpoint of modified Neuropathy Impairment Score +7 (mNIS+7), a measure of neuropathic disease progression, with a statistically significant difference in mean change from baseline versus the external placebo group (p<0.0001). The study met its key secondary endpoint of change from baseline in the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN), showing that treatment with eplontersen significantly improved patient-reported quality of life compared to the external placebo group (p<0.0001). Eplontersen also demonstrated a favorable safety and tolerability profile.
Eplontersen is an investigational medicine designed to reduce the production of transthyretin (TTR) protein to treat both hereditary and non-hereditary forms of ATTR amyloidosis (ATTR). In December 2021, Ionis and AstraZeneca entered into a strategic collaboration to develop and commercialize eplontersen. Eplontersen is being jointly developed and commercialized by both companies in the U.S. and will be developed and commercialized in the rest of the world by AstraZeneca, with the exception of Latin America. In January 2022, eplontersen was granted Orphan Drug Designation in the U.S. by the FDA.
In addition to the NEURO-TTRansform study, eplontersen is also currently being evaluated in the global Phase 3 CARDIO-TTRansform study for transthyretin amyloid cardiomyopathy (ATTR-CM), a systemic, progressive and fatal condition that leads to progressive heart failure and death within three to five years from disease onset.
About Eplontersen
Eplontersen is an investigational LIgand-Conjugated Antisense (LICA) medicine designed to inhibit the production of TTR protein. Eplontersen is being developed as a monthly self-administered subcutaneous injection to treat all types of ATTR. ATTR amyloidosis is a systemic, progressive and fatal disease in which patients experience multiple overlapping clinical manifestations caused by the inappropriate formation and aggregation of TTR amyloid deposits in various tissues and organs, including peripheral nerves, heart, intestinal tract, eyes, kidneys, central nervous system, thyroid and bone marrow. The progressive accumulation of TTR amyloid deposits in these tissues and organs leads to organ failure and eventually death.
About Ionis Pharmaceuticals, Inc.
For more than 30 years, Ionis has been a leader in RNA-targeted therapy, pioneering new markets and changing standards of care with its novel antisense technology. Ionis currently has three marketed medicines and a promising late-stage pipeline highlighted by cardiovascular and neurological franchises. Our scientific innovation began and continues with the knowledge that sick people depend on us, which fuels our vision to become the leader in genetic medicine, utilizing a multi-platform approach to discover, develop and deliver life-transforming therapies.
To learn more about Ionis visit www.ionispharma.com and follow us on Twitter @ionispharma.
View original content to download multimedia:https://www.prnewswire.com/news-releases/ionis-announces-fda-acceptance-of-new-drug-application-for-eplontersen-for-the-treatment-of-hereditary-transthyretin-mediated-amyloid-polyneuropathy-attrv-pn-301764027.html
SOURCE Ionis Pharmaceuticals, Inc.
Ionis, AstraZeneca eplontersen application accepted by FDA for nerve damage disorder
Mar. 07, 2023 12:59 PM ET
By: Jonathan Block, SA News Editor2 Comments
- The US FDA has accepted a New Drug Application submitted by Ionis Pharmaceuticals (NASDAQ:IONS) for eplontersen for hereditary transthyretin-mediated amyloid polyneuropathy (ATTRv-PN).
- The FDA action date is Dec. 22.
- The agency said it does not plan on holding an advisory committee meeting for the application.
- Ionis (IONS) is partnered with AstraZeneca (NASDAQ:AZN) on the candidate.
- https://seekingalpha.com/news/3944994-ionis-astrazeneca-eplontersen-application-accepted-by-fda-for-nerve-damage-disorder
- AstraZeneca PLC (AZN), IONS
- https://www.astrazeneca.com/
- https://www.ionispharma.com/ionis-antisense-technology/antisense-pipeline/
Sotatercept
OPSUMIT® (macitentan) & Tadalafil combo
Eplontersen
Merck’s Investigational Activin Signaling Inhibitor Sotatercept Improved Six-Minute Walk Distance by 40.8 Meters at Week 24 Versus Placebo in Adults with Pulmonary Arterial Hypertension on Background Therapy
March 6, 2023 12:01 pm ET
Sotatercept demonstrated statistically significant improvements in 8 of 9 secondary measures, including reduction in risk of clinical worsening or death
Results presented today at ACC.23/WCC and published in The New England Journal of Medicine
RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced full results from the Phase 3 STELLAR trial, which evaluated sotatercept, Merck’s novel investigational activin signaling inhibitor biologic, in combination with stable background therapy for the treatment of adult patients with pulmonary arterial hypertension (PAH) (WHO Group 1). Sotatercept significantly improved exercise capacity, increasing 6-minute walk distance (6MWD) by 40.8 meters (95% CI, 27.5-54.1; p<0.001) from baseline at week 24, the study’s primary endpoint.
In addition, sotatercept demonstrated statistically significant and clinically meaningful improvements in eight of nine secondary outcome measures, including improvements in WHO functional class (WHO FC) and pulmonary vascular resistance (PVR). Sotatercept reduced the risk of clinical worsening or death by 84% compared to placebo with a median follow-up of 32.7 weeks (HR=0.16 [95% CI, 0.08-0.35]; p<0.001). The safety profile of sotatercept was generally consistent with that observed in previous studies with sotatercept. These data were presented today at the American College of Cardiology’s 72nd Annual Scientific Session together with World Heart Federation’s World Congress of Cardiology and simultaneously published in The New England Journal of Medicine.
“PAH is a rare, rapidly progressive, debilitating and ultimately life-threatening condition with a five-year mortality rate of 43 percent,” said Dr. Marius Hoeper, Hannover Medical School, Germany, and lead investigator. “Sotatercept demonstrated profound improvements across the primary endpoint of six-minute walk distance and multiple secondary endpoints, including improvements in WHO functional class and pulmonary vascular resistance. These landmark results show the potential of sotatercept and the approach of targeting cellular signaling associated with vascular hyperproliferation and pathological remodeling for the treatment of PAH.”
“The results from the Phase 3 STELLAR trial are immensely important to physicians and patients and highlight the critical role sotatercept may play in improving exercise capacity and other meaningful clinical outcome measures for patients with PAH,” said Dr. Dean Y. Li, president, Merck Research Laboratories. “These findings are compelling given the profound reduction in the risk of clinical worsening or death in patients treated with sotatercept on top of background therapy. We look forward to discussing these pivotal data with health authorities and are working with urgency to bring this potential new treatment option to patients.”
STELLAR is the first Phase 3 study to evaluate the efficacy of an activin signaling inhibitor added to background therapy in adults with PAH. Key findings from secondary endpoints included:
- The proportion of patients who achieved multicomponent improvement at week 24 (defined as improvement in 6MWD, improvement in N-terminal pro-B-type natriuretic peptide (NT-proBNP) level, and either improvement in WHO FC or maintenance of WHO FC II) was significantly greater with sotatercept versus placebo (38.9% [n=63/163] versus 10.1% [n=16/160]; p<0.001).
- Sotatercept demonstrated a statistically significant reduction of -234.6 dyn·sec·cm−5 (95% CI, -288.4 to -180.8; p<0.001) from baseline at week 24 in PVR – a calculation of pulmonary artery pressure, pulmonary artery wedge pressure and cardiac output – versus placebo.
- Sotatercept demonstrated a statistically significant reduction of -441.6 (95% CI, -573.5 to -309.6; p<0.001) from baseline at week 24 in NT-proBNP levels versus placebo.
- Patients receiving sotatercept were significantly more likely to improve and maintain WHO FC at week 24 versus placebo. 29.4% (n=48/163) of patients in the sotatercept group improved in WHO FC compared to 13.8% (n=22/160) in the placebo group (p<0.001).
- Sotatercept significantly reduced events associated with clinical worsening (defined by death of any cause or specified non-fatal clinical worsening events). With a median follow-up of 32.7 weeks, 9 of 163 patients in the sotatercept group died or experienced a clinical worsening event versus 42 of 160 patients in the placebo group (HR=0.16 [95% CI, 0.08 to 0.35]; p<0.001).
- A significantly greater proportion of patients treated with sotatercept achieved or maintained a low French risk score (attaining or maintaining all three low-risk criteria: WHO functional class I or II, 6-minute walk distance > 440 meters, and NT-proBNP level < 300 pg per milliliter) versus placebo (39.5% [n=64/163] versus 18.2% [n=29/160]; p<0.001).
- In patient-reported outcomes using the PAH-SYMPACT® questionnaire, the average scores for Physical Impacts (change from baseline: -0.26 [95% CI, -0.49 to -0.04]; p=0.010) and Cardiopulmonary Symptoms (change from baseline: -0.13 [95% CI, -0.26 to -0.01]; p=0.028) were significantly reduced in patients treated with sotatercept versus placebo. PAH-SYMPACT® is a disease-specific patient-reported outcome instrument. Domain scores range from 0 to 4 with higher scores indicating greater severity of symptoms.
- The average score for Cognitive/Emotional Impacts using PAH-SYMPACT® was not significantly different between patients treated with sotatercept versus placebo (p=0.156).
Treatment-emergent adverse events (TEAEs) occurred in 90.8% of patients who received sotatercept versus 91.9% of patients who received placebo, while severe TEAEs were observed in 12.9% versus 18.1% of patients, respectively. Adverse events that occurred more frequently with sotatercept versus placebo were bleeding events, telangiectasia, increased hemoglobin levels, thrombocytopenia, increased blood pressure, and dizziness.
Study design and additional data from the STELLAR trial
STELLAR (NCT04576988) was a pivotal Phase 3, randomized, double-blind, placebo-controlled, multicenter, parallel-group study to evaluate the safety and efficacy of sotatercept in adult patients with PAH (WHO Group 1) being treated with background therapy with WHO Functional Class (FC) II or III. The primary endpoint of the study was exercise capacity, as measured by change from baseline in week 24 6MWD. Nine secondary endpoints, tested hierarchically in the following order, were multicomponent improvement, change in PVR, NT-proBNP level, improvement in WHO FC, time to clinical worsening or death, French risk score, and the PAH-SYMPACT® Physical Impacts, Cardiopulmonary Symptoms and Cognitive/Emotional Impacts domain scores; all assessed at week 24 except clinical worsening, which was assessed when the last patient completed the week 24 visit.
The study enrolled a total of 323 participants who were randomized to receive either sotatercept (n=163) once every 3 weeks at a dose of 0.3 mg/kg at visit 1 and a dose of 0.7 mg/kg thereafter or placebo (n=160) added to stable background PAH therapy. The study population characteristics were: mean [±SD] 47.9 ± 14.8 years of age; 89% white; 79% female; and average length of time since PAH diagnosis of 8.8 years. In total,198 of the randomized patients (61.3%) were receiving triple therapy and 129 patients (39.9%) were receiving prostacyclin infusion therapy. Demographic and baseline characteristics were similar between the sotatercept and placebo groups.
The safety profile of sotatercept was generally consistent with that observed in the Phase 2 PULSAR trial. Seven patients (4.4%) in the placebo group and two patients (1.2%) in the sotatercept group died during the study through the data cutoff date.
About pulmonary arterial hypertension (PAH)
Pulmonary arterial hypertension (PAH) is a rare, progressive and life-threatening blood vessel disorder characterized by the constriction of small pulmonary arteries and elevated blood pressure in the pulmonary circulation. Approximately 40,000 people in the U.S. are living with PAH. The disease progresses rapidly for many patients. PAH results in significant strain on the heart, leading to limited physical activity, heart failure and reduced life expectancy. The five-year mortality rate for patients with PAH is approximately 43%.
About sotatercept
Sotatercept is an investigational, potential first-in-class activin signaling inhibitor biologic being studied for the treatment of PAH (WHO Group 1). PAH is a rare disease caused, in part, by hyperproliferation of cells in the arterial walls in the lung, leading to narrowing and abnormal constriction. In pre-clinical models, sotatercept has been shown to modulate vascular cell proliferation, reversing vascular and right ventricle remodeling.
Sotatercept has been granted Breakthrough Therapy Designation and Orphan Drug designation by the U.S. Food and Drug Administration (FDA), as well as Priority Medicines designation and Orphan Drug designation by the European Medicines Agency for the treatment of PAH. Merck acquired exclusive rights to sotatercept in the pulmonary hypertension field through the acquisition of Acceleron Pharma Inc. Sotatercept is the subject of a licensing agreement with Bristol Myers Squibb.
About Merck
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.
Source: Merck & Co., Inc.
Merck posts full Phase 3 data for sotatercept in pulmonary arterial hypertension
Mar. 07, 2023 5:30 AM ET
By: Dulan Lokuwithana, SA News Editor
Merck (NYSE:MRK) closed ~4% higher Monday, marking the biggest one-day gain since June 2022 after disclosing complete Phase 3 results for biologic sotatercept, which is targeted at blood vessel disorder pulmonary arterial hypertension (PAH).
MK-0616
OPSUMIT® (macitentan) & Tadalafil combo
OPSUMIT® (macitentan) & Tadalafil combo
Merck’s MK-0616, an Investigational Oral PCSK9 Inhibitor, Significantly Reduced LDL-C in Patients with Hypercholesterolemia in Phase 2b Study
March 6, 2023 12:00 pm ET
MK-0616 was generally well tolerated and reduced LDL-C across all dose levels compared to placebo
Merck plans to start Phase 3 pivotal study in the second half of 2023
RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced results from the Phase 2b clinical trial evaluating MK-0616, an investigational, once-daily oral proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor in adults with hypercholesterolemia. The primary objective of the study was to evaluate the percent change in low density lipoprotein cholesterol (LDL-C) from baseline to week 8 for 4 doses of MK-0616 (6, 12, 18 and 30 mg) versus placebo. At week 8, all doses of MK-0616 significantly reduced LDL-C compared to placebo and the placebo-adjusted reduction from baseline ranged from 41.2% (6 mg, CI 95%, -47.8 to -34.7; p <0.001) to 60.9% (30 mg, 95% CI, -67.6 to -54.3; p<0.001). MK-0616 was generally well-tolerated at all 4 doses studied. These data were presented today at the American College of Cardiology’s 72nd Annual Scientific Session together with World Congress of Cardiology (ACC.23/WCC) and simultaneously published in the Journal of The American College of Cardiology.
Inhibition of PCSK9 increases the removal of LDL-C from the bloodstream. MK-0616 is a macrocyclic peptide and is designed to lower LDL-C via the same biological mechanism as currently approved injectable PCSK9 inhibitors, but in a daily pill form. High LDL-C, if left untreated, can lead to a high risk of atherosclerotic cardiovascular disease (ASCVD) events, such as heart attacks and strokes.
“Despite widely available statin treatments, millions of patients are still not able to lower their cholesterol to the guideline-recommended levels and as a result are at increased risk for serious cardiovascular complications associated with atherosclerosis,” said Dr. Christie M. Ballantyne, principal investigator of the study and Professor of Medicine at Baylor College of Medicine. “Currently available PCSK9 inhibitors are effective tools to treat hypercholesterolemia but must be administered by injection. With these promising data showing that MK-0616 reduced LDL-C levels by up to 60.9%, MK-0616 should be further studied for its potential as a daily oral medicine.”
“These data reinforce our confidence that MK-0616 could become the first oral PCSK9 inhibitor, with the potential to change the way patients with hypercholesterolemia who need additional LDL-C reduction are treated. This may allow many more patients to reach their LDL-C treatment goals,” said Dr. Joerg Koglin, vice president, global clinical development, Merck Research Laboratories. “We look forward to advancing this program into Phase 3 development in the second half of this year.”
Additional data from the Phase 2b Study for MK-0616 (MK-0616-008)
MK-0616-008(NCT05261126) was a randomized, double-blind, placebo-controlled, multi-center Phase 2b trial designed to evaluate the efficacy and safety of MK-0616 administered daily compared to placebo in adult participants with hypercholesterolemia and a broad spectrum of ASCVD risk. Participants were receiving a range of lipid-lowering therapies from no statin to high-intensity statin. The primary efficacy endpoint was the percent change in LDL-C from baseline to week 8. Supportive secondary endpoints (not multiplicity controlled) were percent change in apolipoprotein B-100 (ApoB) and in non-high-density lipoprotein-C (non-HDL-C) from baseline to week 8, and the proportion of participants who achieved protocol-defined LDL-C goals at week 8.
In total, 381 participants from age 18-80 with hypercholesterolemia with a moderate to high risk of atherosclerotic cardiovascular disease were randomized 1:1:1:1:1 to receive MK-0616 at a dose of 6 mg (n=77), 12 mg (n=76), 18 mg (n=76), or 30 mg (n=76) or placebo (n=76) once daily. The study population consisted of 49% female, 66% White, 17% Asian and 6% Black/African American, and 40% Latino or Hispanic.
At week 8, all doses of MK-0616 significantly reduced LDL-C compared to placebo and the results were generally consistent across the prespecified subgroups. The LDL-C placebo-adjusted reduction from baseline were as follows for each of the four doses studied (p<0.001 for all doses): 6 mg, 41.2% (95% CI, -47.8, -34.7), 12 mg, 55.7% (95% CI, -62.3, -49.1), 18 mg, 59.1% (95% CI, -65.7, -52.5), and 30 mg, 60.9% (95% CI, -67.6, -54.3). Near-complete efficacy was achieved by week 2, with the effect persisting over the eight-week treatment period. At week 8, improvements in secondary endpoints were also observed for all MK-0616 dose arms: ApoB levels were reduced by 32.8% (6 mg) to 51.8% (30 mg), non-HDL-C levels were reduced by 35.9% (6 mg) to 55.8% (30 mg), and protocol-defined LDL-C goals were achieved by 80.5% (6 mg) to 90.8% of participants (30 mg) versus 9.3% on placebo.
MK-0616 was generally well-tolerated with no overall trends across treatment groups in discontinuation rates or adverse events at week 16. No serious adverse events that were considered by the investigator to be related to treatment with MK-0616 were reported.
About PCSK9 and MK-0616
PCSK9 plays a key role in cholesterol homeostasis by regulating levels of LDL receptors, which are responsible for the uptake of cholesterol into cells. Inhibition of PCSK9 prevents the interaction of PCSK9 with LDL receptors. This results in greater numbers of LDL receptors available on the cell surface to remove LDL cholesterol from the blood.
Discovered and developed by Merck, MK-0616 is an investigational, potentially first oral PCSK9 inhibitor designed to lower low density lipoprotein (LDL) cholesterol. MK-0616 is a macrocyclic peptide that binds to PCSK9 and inhibits the interaction of PCSK9 with LDL receptors.
About Hypercholesterolemia
Hypercholesterolemia, a disorder in which there are elevated LDL-C levels in the blood, affects approximately 73 million adults in the U.S. It is a major risk factor associated with ASCVD, which is the leading cause of death in the U.S. and globally. Despite adjusting diet and taking statin therapies, many patients with hypercholesterolemia are still not reaching their LDL-C lowering goals as recommended by guidelines.
Merck’s Focus on Cardiovascular and Pulmonary Disease
Merck has a long history of developing treatments for cardiovascular disease. More than 60 years ago, we introduced our first cardiovascular therapy – and our scientific efforts to understand and treat cardiovascular-related disorders have continued. Cardiovascular disease continues to be one of the most serious health challenges of the 21st century. Approximately 18 million people across the globe die every year, and in the United States, one person dies every 36 seconds from cardiovascular disease.
Advancements in the treatment of cardiovascular disease can make a critical difference for patients around the world. At Merck, we strive for scientific excellence and innovation in all stages of research, from discovery through approval and life cycle management. We work with experts throughout the cardiovascular and pulmonary community to advance research that can help improve the lives of patients globally.
Information for other currently enrolling cardiovascular studies can be found by visiting: https://www.merckclinicaltrials.com/cardiovascular.
About Merck
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.
Source: Merck & Co., Inc.
Merck to start phase 3 of oral PCSK9 inhibitor for cholesterol following mid-stage results
Mar. 06, 2023 1:45 PM ET
Merck & Co., Inc. (MRK)AMGN, NVS, REGN
By: Jonathan Block, SA News Editor
- Phase 2b data for Merck's (NYSE:MRK) oral PCSK9 inhibitor MK-0616 has prompted the drugmaker to begin a phase 3 program in the second half of the year.
- https://seekingalpha.com/news/3944574-merck-to-start-phase-3-of-oral-pcsk9-inhibitor-for-cholesterol-following-mid-stage-results
- Merck & Co., Inc. (MRK)
OPSUMIT® (macitentan) & Tadalafil combo
OPSUMIT® (macitentan) & Tadalafil combo
OPSUMIT® (macitentan) & Tadalafil combo
Late-Breaking Phase 3 A DUE Data Show Investigational Single Tablet Combination Therapy of Macitentan and Tadalafil Significantly Improves Pulmonary Hemodynamics versus Monotherapy in Patients with Pulmonary Arterial Hypertension (PAH)
Mar 06, 2023United States
Study findings presented during the American College of Cardiology’s 72nd Annual Scientific Session & Expo Together With World Heart Federation’s World Congress of Cardiology
European Society of Cardiology/European Respiratory Society (ESC/ERS) PH guidelines recommend initial dual combination therapy with macitentan and tadalafil for PAH patients without cardiopulmonary comorbidities
RARITAN, NJ, March 6, 2023 – The Janssen Pharmaceutical Companies of Johnson & Johnson today announced results from the Phase 3 A DUE study (NCT03904693), which showed an investigational once-daily, single tablet combination therapy, also known as fixed dose combination, of macitentan 10 mg and tadalafil 40 mg (M/T STCT), significantly improved pulmonary hemodynamics (blood flow through pulmonary blood vessels) versus macitentan and tadalafil monotherapies in pulmonary arterial hypertension (PAH) patients with World Health Organization (WHO) functional class (FC) II or III.[1] The data were presented today as a Late-Breaking Clinical Trial presentation during the American College of Cardiology’s 72nd Annual Scientific Session & Expo Together With World Heart Federation’s World Congress of Cardiology.
PAH is a rare, progressive and life-threatening blood vessel disorder characterized by the constriction of small pulmonary arteries and elevated blood pressure in the pulmonary circulation that eventually leads to right heart failure.[2] Recently updated European Society of Cardiology/European Respiratory Society (ESC/ERS) PH guidelines[i] have recommended initial dual combination therapy with macitentan and tadalafil for PAH patients without cardiopulmonary comorbidities. Currently, this requires patients to take multiple pills as no single tablet that combines two or more PAH-specific pathways is available for these patients.[3]
“Targeting different pathways in the treatment of PAH has demonstrated clear clinical benefits, yet current treatment regimens are cumbersome and create a significant pill burden for patients, many of whom take a large number of pills each day to treat their PAH and various co-morbidities,[ii],[iii]” said Kelly Chin, M.D., Professor of Internal Medicine and Director of the Pulmonary Hypertension Program at UT Southwestern Medical Center, and an investigator in the A DUE study.[4] “The results from this study demonstrate that a single tablet combination has the potential to support initial dual combination therapy and rapid escalation from monotherapy, which may improve functional outcomes and help close the gap from guideline recommendations to clinical practice.”
The A DUE study is a double-blind, randomized, active-controlled, multi-center, adaptive parallel-group study designed to compare the efficacy and safety of investigational M/T STCT versus macitentan and tadalafil monotherapies in patients with PAH. A total of 187 adult PAH patients from across 148 sites in 19 countries worldwide in WHO FC II or III who were treatment naïve or on a stable dose of an endothelin receptor antagonist (ERA) or a phosphodiesterase type 5 inhibitor (PDE5i) for at least three months, were enrolled in the study. The primary endpoint is pulmonary vascular resistance (PVR) measured 16 weeks following initiation of treatment expressed as the ratio of geometric means to baseline.
Secondary efficacy outcome measures included change from baseline in exercise capacity as measured by change in 6-minute walk distance (6MWD) at the end of double-blind treatment at week 16 compared to baseline.
Following the double-blind treatment period, patients transitioned to the open-label treatment period for 24 months. Baseline characteristics were balanced across treatment arms except for a higher proportion of WHO FC II patients in the M/T STCT arm and a greater time from diagnosis of PAH in the macitentan arm.
“The guiding light of our PH research is the goal of transforming PAH into a manageable condition, so we’re constantly looking for ways to improve both clinical outcomes and the treatment experience,” said James List, M.D., Ph.D., Global Therapeutic Area Head, Cardiovascular, Metabolism, Retina & Pulmonary Hypertension, Janssen Research & Development, LLC. “A single tablet combination has the potential to be an important new option for helping physicians optimize disease management with the potential to enhance convenience and help improve adherence and outcomes.”
Key A DUE Study Findings
The A DUE study met its co-primary endpoint, demonstrating marked pulmonary hemodynamic improvement as shown by the highly statistically significant, consistent and robust PVR reduction in participants treated with M/T STCT compared to both monotherapies. PVR change with M/T STCT was significantly greater versus macitentan (treatment effect: 29%; 95% confidence limit [CL]: -18%, -39%, p<0.0001). PVR change with M/T STCT was also significantly greater versus tadalafil (treatment effect: 28%; 95% CL: -20%, -36%, p<0.0001).
Although the A DUE study was not powered to demonstrate a benefit on exercise capacity, there was a clinically relevant improvement in 6MWD.
- At week 16, treatment effect was not statistically significant; however, a clinically relevant improvement in 6MWD in favor of M/T STCT versus monotherapies was observed. Adjusted treatment effect in 6MWD, change from baseline, in the M/T STCT versus macitentan group was 16.04m (CL: -17.0, 49.08, p=0.380) and 25.37m in the M/T STCT versus tadalafil group (CL: -0.93, 51.59, p =0.059).
- The safety profile of M/T STCT was consistent with the known safety profiles of macitentan and tadalafil monotherapies and no new safety observations were made.
About macitentan/tadalafil STCT
Macitentan 10 mg and tadalafil 40 mg STCT is an investigational therapy that combines the ERA, macitentan, and the PDE5i, tadalafil.
About OPSUMIT® (macitentan)
OPSUMIT® is indicated for the treatment of PAH (WHO Group I) to reduce the risks of disease progression and hospitalization for PAH. The use of OPSUMIT® in patients with PAH (WHO Group I), a type of PH, was demonstrated in the pivotal SERAPHIN trial, the largest (n=742) long-term (average treatment duration=2 years) outcomes-based trial of an ERA in PAH.
About tadalafil
Tadalafil is indicated for the treatment of PAH (WHO Group 1) to improve exercise ability. Studies establishing effectiveness included predominately patients with NYHA Functional Class II – III symptoms and etiologies of idiopathic or heritable PAH (61%) or PAH associated with connective tissue diseases (23%).
OPSUMIT® INDICATION AND IMPORTANT SAFETY INFORMATION
INDICATION
OPSUMIT® (macitentan) is an endothelin receptor antagonist (ERA) indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to reduce the risks of disease progression and hospitalization for PAH.
Effectiveness was established in a long-term study in PAH patients with predominantly WHO Functional Class II-III symptoms treated for an average of 2 years. Patients had idiopathic and heritable PAH (57%), PAH caused by connective tissue disorders (31%), and PAH caused by congenital heart disease with repaired shunts (8%).
Please see full Prescribing Information, including BOXED WARNING.
About the Janssen Pharmaceutical Companies of Johnson & Johnson
At Janssen, we’re creating a future where disease is a thing of the past. We’re the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular, Metabolism & Retina; Immunology; Infectious Diseases & Vaccines; Neuroscience; Oncology; and Pulmonary Hypertension.
Learn more at www.janssen.com. Follow us at @JanssenGlobal and @JanssenUS. Janssen Research & Development, LLC is part of the Janssen Pharmaceutical Companies of Johnson & Johnson.
Janssen's macitentan, tadalafil combo improves pulmonary hemodynamics vs. monotherapies
Mar. 06, 2023 10:00 AM ET
By: Mamta Mayani, SA News Editor
- The Janssen Pharmaceutical Companies of Johnson & Johnson <<JNJ>> announces results from the Phase 3 A DUE study, which showed an investigational once-daily, single tablet combination therapy, also known as fixed dose combination, of macitentan 10 mg and tadalafil 40 mg (M/T STCT), significantly improved pulmonary hemodynamics (blood flow through pulmonary blood vessels) versus macitentan and tadalafil monotherapies in pulmonary arterial hypertension (PAH) patients with WHO functional class (FC) II or III.
- https://seekingalpha.com/news/3944464-janssens-macitentan-tadalafil-combo-improves-pulmonary-hemodynamics-vs-monotherapies
- JNJ
- https://www.janssen.com/
biotecHOPE™ 2023
IK-175
TRUSELTIQ (high-dose infigratinib)
LEQEMBI™ (lecanemab-irmb)
Ikena Oncology Receives FDA Fast Track Designation for Novel AHR Antagonist IK-175 in Combination with Immune Checkpoint Inhibitors to Treat Urothelial Carcinoma
Mar 06, 2023
BOSTON, March 06, 2023 (GLOBE NEWSWIRE) -- Ikena Oncology, Inc. (Nasdaq: IKNA, “Ikena”), a targeted oncology company forging new territory in patient-directed cancer treatment, today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for IK-175, the Company’s novel aryl hydrocarbon receptor (AHR) antagonist, in combination with immune checkpoint inhibitors in patients with advanced urothelial carcinoma who have progressed on or within three months of receiving the last dose of checkpoint inhibitors.
Fast Track designation is reserved for therapies that represent potential best-in-class therapeutic options for diseases with high unmet need. Therapies that receive Fast Track designation often have the opportunity to communicate more frequently with the FDA on trial design and data and may also be eligible for priority review and accelerated approval. IK-175 is the second of Ikena’s candidates to receive Fast Track designation; the FDA has also granted the designation to IK-930, the Company’s novel TEAD inhibitor, in patients with unresectable NF2-deficient malignant pleural mesothelioma.
“There is an urgent need for new treatment options for urothelial carcinoma patients, many of whom find themselves out of options after progressing on checkpoint inhibitors. The Fast Track designation for IK-175 reflects the FDA’s interest in the potential role of our AHR antagonist to overcome the development of resistance to checkpoint inhibitors and supports our strategy of combining IK-175 with nivolumab to expand the number of cancer patients that can benefit from immunotherapy,” said Sergio Santillana, MD, Chief Medical Officer at Ikena.
IK-175 targets AHR, a compelling cancer-driving transcription factor that prevents immune recognition in a multitude of cancers by modulation of innate and adaptive immunity. Patients with urothelial carcinoma are generally treated through a combination of standard-of-care options, including surgery, chemotherapy, radiation and immunotherapies, including checkpoint inhibitors.
IK-175 is currently being studied in a Phase 1a/b clinical trial as a monotherapy and in combination with nivolumab in patients with advanced or metastatic solid tumors including urothelial carcinoma for which standard therapy is no longer effective or is intolerable (NCT04200963, or IK-175-001). Initial clinical data presented at the Society for Immunotherapy of Cancer (SITC) 2022 Annual Meeting demonstrated that IK-175 is well tolerated and showed encouraging, durable, anti-tumor activity in stage 1 of the trial’s monotherapy and combination arms in urothelial carcinoma patients. The IK-175 program is being developed in collaboration with Bristol Myers Squibb and they have an option to exclusively license the program through early 2024.
About Ikena Oncology
Ikena Oncology™ is focused on developing differentiated therapies for patients in need that target nodes of cancer growth, spread, and therapeutic resistance in the Hippo and RAS onco-signaling network. The Company’s lead targeted oncology program, IK-930, is a paralog-selective TEAD inhibitor addressing the Hippo signaling pathway, a known tumor suppressor pathway that also drives resistance to multiple targeted therapies. The Company’s additional research spans other targets in the Hippo pathway as well as the RAS signaling pathway, including developing IK-595, a novel MEK-RAF inhibitor. Additionally, IK-175, an AHR antagonist, is being developed in collaboration with Bristol Myers Squibb. Ikena aims to utilize their depth of institutional knowledge and breadth of tools to efficiently develop the right drug using the right modality for the right patient. To learn more, visit www.ikenaoncology.com or follow us on Twitter and LinkedIn.
Ikena gains on FDA’s fast track status for bladder cancer candidate
Mar. 06, 2023 8:42 AM ET
Ikena Oncology, Inc. (IKNA)BMY
By: Dulan Lokuwithana, SA News Editor
- Ikena Oncology (NASDAQ:IKNA) added ~9% pre-market Monday after the cancer-focused pharma company announced the FDA’s Fast Track designation for IK-175, a candidate targeted at urothelial carcinoma.
- https://seekingalpha.com/news/3944409-ikna-stock-gains-fdas-fast-track-status-bladder-cancer-candidate
- Ikena Oncology, Inc. (IKNA)
- https://ikenaoncology.com/pipeline/
LEQEMBI™ (lecanemab-irmb)
TRUSELTIQ (high-dose infigratinib)
LEQEMBI™ (lecanemab-irmb)
FDA Accepts Eisai’s Filing of a Supplemental Biologics License Application and Grants Priority Review for Traditional Approval of LEQEMBI™ (lecanemab-irmb) for the Treatment of Alzheimer’s Disease
MARCH 5, 2023 • NEWS RELEASE
Confirmatory Phase 3 Clarity AD data to be evaluated by FDA in determining whether to convert accelerated approval of LEQEMBI to a traditional approval
Priority Review accelerates FDA review time with a Prescription Drug User Fee Act (PDUFA) target action on July 6, 2023
TOKYO and CAMBRIDGE, Mass., March 05, 2023 (GLOBE NEWSWIRE) -- Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") and Biogen Inc. (Nasdaq: BIIB, Corporate headquarters: Cambridge, Massachusetts, CEO: Christopher A. Viehbacher, "Biogen") announced today that the U.S. Food and Drug Administration (FDA) has accepted Eisai’s supplemental Biologics License Application (sBLA) for LEQEMBI™ (lecanemab-irmb) 100 mg/mL injection for intravenous use, supporting the conversion of the accelerated approval of LEQEMBI to a traditional approval. The LEQEMBI application has been granted Priority Review, with a Prescription Drug User Fee Act (PDUFA) action date of July 6, 2023. The FDA is currently planning to hold an Advisory Committee to discuss this application but has not yet publicly announced the date of the meeting.
LEQEMBI is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble (protofibrils*) and insoluble forms of amyloid beta (Aβ), approved under the Accelerated Approval Pathway for the treatment of Alzheimer's Disease (AD) on January 6, 2023. Treatment with LEQEMBI should only be initiated in patients with the mild cognitive impairment or mild dementia stage of disease and confirmed presence of Aβ pathology. On the same day that LEQEMBI received its accelerated approval, Eisai submitted the sBLA to the FDA for approval under the traditional pathway.
The sBLA is based on the findings from Eisai’s recently published large, global confirmatory Phase 3 clinical trial, Clarity AD. LEQEMBI met the primary endpoint and all key secondary endpoints with highly statistically significant results. In November 2022, results of the Clarity AD study were presented at the Clinical Trials on Alzheimer's Disease (CTAD) conference and simultaneously published in the peer-reviewed medical journal, The New England Journal of Medicine.
LEQEMBI was approved under accelerated approval in the U.S. and was launched in the U.S. on January 18, 2023. The accelerated approval was based on Phase 2 data that demonstrated that LEQEMBI reduced the accumulation of Aβ plaque in the brain, a defining feature of AD, and its continued approval may be contingent upon verification of LEQEMBI’s clinical benefit in a confirmatory trial. The FDA has determined that the results of Clarity AD can serve as the confirmatory study to verify the clinical benefit of lecanemab.
Eisai serves as the lead of LEQEMBI development and regulatory submissions globally with both Eisai and Biogen co-commercializing and co-promoting the product and Eisai having final decision-making authority.
* Protofibrils are large Aβ aggregated soluble species of 75-500 Kd.1
To learn more, visit www.LEQEMBI.com.
INDICATION, DOSAGE AND ADMINISTRATION, AND IMPORTANT SAFETY INFORMATION IN THE U.S.
INDICATION
LEQEMBI is indicated for the treatment of Alzheimer’s disease. Treatment with LEQEMBI should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. There are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied. This indication is approved under accelerated approval based on reduction in amyloid beta plaques observed in patients treated with LEQEMBI. Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial.
Please see full Prescribing Information in the U. S.
About LEQEMBITM (lecanemab-irmb)
LEQEMBITM (lecanemab-irmb) is the result of a strategic research alliance between Eisai and BioArctic. LEQEMBI is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble (protofibril) and insoluble forms of amyloid-beta (Aβ). In the U.S., LEQEMBI was granted accelerated approval by the U.S. Food and Drug Administration (FDA) on January 6, 2023. LEQEMBI is indicated for the treatment of Alzheimer’s disease (AD) in the U.S. Treatment with LEQEMBI should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. There are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied. This indication is approved under accelerated approval based on reduction in Aβ plaques observed in patients treated with LEQEMBI. Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial.
In the U.S., Eisai submitted a supplemental Biologics License Application (sBLA) to the FDA for approval under the traditional pathway on January 6, 2023. The Clarity AD study of lecanemab met its primary endpoint and all key secondary endpoints with highly statistically significant results. Eisai submitted an application for manufacturing and marketing approval to the Pharmaceuticals and Medical Devices Agency (PMDA) on January 16, 2023, in Japan. The Priority Review was granted by the Ministry of Health, Labour and Welfare (MHLW) on January 26, 2023. Eisai utilized the prior assessment consultation system of PMDA, with the aim of shortening the review period for lecanemab. In Europe, Eisai submitted a marketing authorization application (MAA) to the European Medicines Agency (EMA) on January 9, 2023, and accepted on January 26, 2023. In China, Eisai initiated submission of data for a BLA to the National Medical Products Administration (NMPA) of China in December 2022, and the Priority Review was granted on February 27, 2023.
Eisai has completed lecanemab subcutaneous bioavailability study, and subcutaneous dosing is currently being evaluated in the Clarity AD OLE.
Since July 2020, Eisai's Phase 3 clinical study (AHEAD 3-45) for individuals with preclinical AD, meaning they are clinically normal and have intermediate or elevated levels of amyloid in their brains, is ongoing. AHEAD 3-45 is conducted as a public-private partnership between the Alzheimer's Clinical Trial Consortium (ACTC) that provides the infrastructure for academic clinical trials in AD and related dementias in the U.S., funded by the National Institute on Aging, part of the National Institutes of Health, Eisai and Biogen. The Tau NexGen clinical study for Dominantly Inherited AD (DIAD), that is conducted by Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU), led by Washington University School of Medicine in St. Louis, has been ongoing since January 2022.
2. About the Collaboration between Eisai and Biogen for AD
Eisai and Biogen have been collaborating on the joint development and commercialization of AD treatments since 2014. Eisai serves as the lead of lecanemab development and regulatory submissions globally with both companies co-commercializing and co-promoting the product and Eisai having final decision-making authority.
3. About the Collaboration between Eisai and BioArctic for AD
Since 2005, Eisai and BioArctic have had a long-term collaboration regarding the development and commercialization of AD treatments. Eisai obtained the global rights to study, develop, manufacture and market LEQEMBI for the treatment of AD pursuant to an agreement with BioArctic in December 2007. The development and commercialization agreement on the antibody LEQEMBI back-up was signed in May 2015.
4. About Eisai Co., Ltd.
Eisai's Corporate Concept is "to give first thought to patients and people in the daily living domain, and to increase the benefits that health care provides." Under this concept (also known as the human health care [hhc] concept), we aim to effectively achieve social good in the form of relieving anxiety over health and reducing health disparities. With a global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to create and deliver innovative products to target diseases with high unmet medical needs, with a particular focus in our strategic areas of neurology and oncology.
In addition, we demonstrate our commitment to the elimination of neglected tropical diseases (NTDs), which is a target (3.3) of the United Nations Sustainable Development Goals (SDGs), by working on various activities together with global partners.
For more information about Eisai, please visit www.eisai.com (for global headquarters: Eisai Co., Ltd.), and connect with us on Twitter @Eisai_SDGs.
5. About Biogen
Founded in 1978, Biogen is a leading global biotechnology company that has pioneered multiple breakthrough innovations including a broad portfolio of medicines to treat multiple sclerosis, the first approved treatment for spinal muscular atrophy, and two co-developed treatments to address a defining pathology of Alzheimer’s disease. Biogen is advancing a pipeline of potential novel therapies across neurology, neuropsychiatry, specialized immunology and rare diseases and remains acutely focused on its purpose of serving humanity through science while advancing a healthier, more sustainable and equitable world.
The company routinely posts information that may be important to investors on its website at www.biogen.com. Follow Biogen on social media – Twitter, LinkedIn, Facebook, YouTube.
Biogen, Eisai's Alzheimer's drug Leqembi gets FDA priority review for traditional approval
Mar. 06, 2023 4:34 AM ET
Biogen Inc. (BIIB)ESALF, BRCTF, ESAIY
By: Ravikash, SA News Editor
The U.S. Food and Drug Administration (FDA) granted priority review to Biogen's (NASDAQ:BIIB) application seeking traditional approval of Alzheimer's disease (AD) therapy Leqembi (lecanemab) from its current status of accelerated approval.
TRUSELTIQ (high-dose infigratinib)
TRUSELTIQ (high-dose infigratinib)
MMRV Family of Vaccines -ProQuad, M-M-R®II, and VARIVAX
BridgeBio Announces Positive Phase 2 Cohort 5 Results of Infigratinib in Achondroplasia Demonstrating Mean Increase in Annualized Height Velocity of 3.03 cm/year with No Treatment-related Adverse Events
– In the highest dose level (Cohort 5, 0.25 mg/kg once daily), the mean change from baseline in annualized height velocity (AHV) at six months was +3.03 cm/yr (p = 0.0022) for the first 10 children with at least six months of follow-up in Cohort 5. The two remaining children who have not yet had six months of follow-up have a mean change from baseline in AHV of +8.8 cm/yr based on three months data
– 80% of children at six months were responders, as defined by an increase from baseline AHV of at least 25%. The mean change from baseline in AHV of responders was 3.81 cm/yr
– As a result of treatment, the median absolute AHV reached 7.6 cm/yr, which is beyond the 99th percentile of growth for children living with achondroplasia
– Infigratinib demonstrated clear dose-responsiveness as a single daily oral therapy and was well-tolerated with no adverse events (AEs) assessed as treatment-related in Cohort 5
– Based on the positive Phase 2 results, BridgeBio has started to enroll children for a pivotal Phase 3 trial
– BridgeBio expects to initiate clinical development of infigratinib for hypochondroplasia, a skeletal dysplasia closely related to achondroplasia and driven by fibroblast growth factor receptor 3 (FGFR3) gain-of-function variants, and will continue to explore the impact on the medical and functional complications of achondroplasia in future studies of infigratinib
PALO ALTO, Calif., March 06, 2023 (GLOBE NEWSWIRE) — BridgeBio Pharma, Inc. (Nasdaq: BBIO) (BridgeBio), a commercial-stage biopharmaceutical company focused on genetic diseases and cancers, today announced positive results from PROPEL2, a Phase 2 trial of the investigational therapy infigratinib in children with achondroplasia, demonstrating potential best-in-class efficacy and a clean safety profile. Infigratinib is an oral small molecule designed to inhibit FGFR3 and target achondroplasia at its source. BridgeBio will also host an investor call on March 6, 2023, at 7:30 am ET to discuss the results from the Phase 2 study.
To date, key results from the clinical trial include:
- At the highest dose level evaluated to date (Cohort 5, 0.25 mg/kg once daily), the mean increase from baseline in annualized height velocity (AHV) for the 10 children that have had six-month visits was +3.03 cm/yr (p = 0.0022). Individual data can be found in Figure 1 below
- The baseline AHV for the 10 children with six-month visits was in the expected range for children with achondroplasia at 3.73 cm/yr, rising to 6.77 cm/yr after treatment
- The two remaining children who have not yet had six months of follow-up have a mean change from baseline in AHV of +8.8 cm/yr at three months. The mean age for the cohort was 7.24 years
- 80% of the 10 children with six-month visits were responders, with a change from baseline AHV of at least 25%. Among the responders, the average change from baseline in AHV was +3.81 cm/yr
- Preliminary analysis of Collagen X (CXM) levels also saw a statistically significant increase from baseline in Cohort 5 (p=.03). CXM is the gold-standard biomarker of chondrocyte-driven growth and further validates the robust response to infigratinib
- Combined with the previously reported Cohort 4 change from baseline in AHV value of +1.52 cm/yr, the Cohort 5 data demonstrate a strong dose response for infigratinib
- Median follow-up across all cohorts is 71.1 weeks. To date, the study has shown a well-tolerated safety profile, with no study drug related treatment emergent adverse events (TEAEs) in Cohort 5. No serious adverse events (SAEs) or discontinuations due to AEs were reported in any cohort
Figure 1
“The data from Cohort 5 has shown a major impact on annualized height velocity for children with achondroplasia and an excellent safety profile to date. We are thrilled to see these promising results and consider that AHV increases of this magnitude will translate to improvements in the medical and functional complications of achondroplasia. We are excited about taking the next steps towards initiating a Phase 3, pivotal clinical trial,” said Professor Ravi Savarirayan, M.D., Ph.D., clinical geneticist and group leader of molecular therapies research at the Murdoch Children’s Research Institute in Australia, the lead investigator for PROPEL2.
“I am encouraged by these efficacy and safety results and thankful for our partnership with the physicians, community advocates, children, and families in this study. These results reach a new tier of efficacy, and coupled with our differentiated safety and convenience profile, provide us the opportunity to serve children with achondroplasia and other skeletal dysplasias. We look forward to exploring the potential of infigratinib on the wider medical and functional impacts of achondroplasia, hypochondroplasia and other skeletal dysplasias, which hold significant unmet needs for families,” said Neil Kumar, Ph.D., founder and CEO of BridgeBio.
Based on the positive results to date, BridgeBio has started enrolling children in the run-in for a Phase 3 trial. Additionally, BridgeBio expects to initiate clinical development for infigratinib in hypochondroplasia, a skeletal dysplasia closely related to achondroplasia and similarly driven by FGFR3 gain-of-function variants. BridgeBio has previously presented promising preclinical data for hypochondroplasia at ENDO 2022 and ASHG 2022.
“Achondroplasia can have broad impact that affects the whole person. People can experience a range of medical complications, including foramen magnum stenosis, spinal stenosis, cardiovascular complications, sleep-disordered breathing, obesity, and sometimes, individuals may need surgical intervention. In addition to the potential medical and physical complications, people with achondroplasia may also experience social and emotional impacts as a result of living with the condition. We are encouraged by BridgeBio’s mission to develop a therapy with the potential to address this as a whole-person condition that affects the overall health, independent function, and quality of life of those with achondroplasia,” said Dianne Kremidas, executive director of The MAGIC Foundation.
Infigratinib has IP protection out to at least 2041.
Webcast Information
BridgeBio will host an investor call and simultaneous webcast to discuss the Phase 2 data from Cohort 5 of infigratinib in children with achondroplasia on March 6, 2023 at 7:30 am ET. A link to the webcast may be accessed from the event calendar page of BridgeBio’s website at https://investor.bridgebio.com/.
A replay of the conference call and webcast will be archived on the Company’s website and will be available for at least 30 days following the event.
About Achondroplasia
Achondroplasia is the most common cause of disproportionate short stature, affecting approximately 55,000 people in the United States (US) and European Union (EU), including up to 10,000 children and adolescents with open growth plates. Achondroplasia impacts overall health and quality of life, leading to medical complications such as obstructive sleep apnea, middle ear dysfunction, kyphosis, and spinal stenosis. The condition is uniformly caused by an activating mutation in FGFR3.
About BridgeBio Pharma, Inc.
BridgeBio Pharma (BridgeBio) is a commercial-stage biopharmaceutical company founded to discover, create, test and deliver transformative medicines to treat patients who suffer from genetic diseases and cancers with clear genetic drivers. BridgeBio’s pipeline of development programs ranges from early science to advanced clinical trials. BridgeBio was founded in 2015 and its team of experienced drug discoverers, developers and innovators are committed to applying advances in genetic medicine to help patients as quickly as possible. For more information visit bridgebio.com and follow us on LinkedIn and Twitter.
BridgeBio soars 55% after Phase 2 data for achondroplasia candidate
Mar. 06, 2023 8:21 AM ET
By: Dulan Lokuwithana, SA News Editor
BridgeBio Pharma (NASDAQ:BBIO) jumped ~55% pre-market Monday after announcing Phase 2 data for infigratinib, which is an investigational therapy for children with achondroplasia, the most common cause of disproportionate short stature.
MMRV Family of Vaccines -ProQuad, M-M-R®II, and VARIVAX
MMRV Family of Vaccines -ProQuad, M-M-R®II, and VARIVAX
MMRV Family of Vaccines -ProQuad, M-M-R®II, and VARIVAX
US FDA Approves Intramuscular Administration for Merck’s MMRV Family of Vaccines: M-M-RII (Measles, Mumps, and Rubella Virus Vaccine Live), VARIVAX (Varicella Virus Vaccine Live), and ProQuad (Measles, Mumps, Rubella and Varicella Virus Vaccine Live)
March 6, 2023 6:45 am ET
With this additional route of administration, the MMRV Family now joins other routinely recommended vaccines that can be administered intramuscularly
RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced today that the U.S. Food and Drug Administration (FDA) has approved the addition of the intramuscular (IM) route of administration to the United States Product Insert (USPI) for Merck’s MMRV family of vaccines: M-M-R®II, VARIVAX®, and ProQuad®.
While these vaccines have a long history in the U.S., until now they have only been administered via subcutaneous (SC) injection.
“Building on our history of innovation in the world of vaccines, we’re proud to introduce another method of administration for M-M-R®II, VARIVAX®, and ProQuad® vaccines, which have been important in the fight against measles, mumps, rubella, and varicella in the U.S.,” said Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories.
With these approvals, healthcare professionals now have the option to choose to administer all routinely recommended injectable pediatric vaccinations included in the CDC immunization schedule, via the same IM route. In the U.S., the only measles, mumps, rubella, and varicella vaccines that can be administered IM are M-M-R®II, VARIVAX®, and ProQuad®. Additionally, the MMRV family of vaccines has already been licensed for IM administration in the European Union.
“As a pediatrician who routinely vaccinates children, I am excited to now have the option to administer these vaccines intramuscularly,” said Dr. Todd Wolynn, co-founding pediatrician of Kids Plus Pediatrics. “This approval provides our practice with an additional route of administration.”
About the MMRV Family of Vaccines
ProQuad® is a vaccine indicated for active immunization for the prevention of measles, mumps, rubella, and varicella in children 12 months through 12 years of age. It was approved by the FDA in 2005. VARIVAX® is a vaccine indicated for active immunization for the prevention of varicella in individuals 12 months of age or older. It received FDA approval in 1995 and remains the only varicella vaccine available for use in the U.S. M-M-R®II is indicated for active immunization for the prevention of measles, mumps, and rubella in individuals 12 months of age or older and received FDA approval in 1978.
Indications and Usage
ProQuad is a vaccine indicated for active immunization for the prevention of measles, mumps, rubella, and varicella in children 12 months through 12 years of age.
VARIVAX is a vaccine indicated for active immunization for the prevention of varicella in individuals 12 months of age or older.
M-M-R®II is indicated for active immunization for the prevention of measles, mumps, and rubella in individuals 12 months of age or older.
Dosage and Administration
ProQuad:
Each dose of ProQuad is approximately 0.5 mL and is administered intramuscularly or subcutaneously.
At least 1 month should elapse between a dose of a measles-containing vaccine such as M-M-R®II and a dose of ProQuad. At least 3 months should elapse between a dose of varicella-containing vaccine and ProQuad.
VARIVAX:
Each dose is approximately 0.5 mL and is administered intramuscularly or subcutaneously.
The first dose is administered at 12 to 15 months of age. The second dose is administered at 4 to 6 years of age. There should be a minimum interval of 3 months between doses. 12 months to 12 years of age: If a second dose is administered, there should be a minimum interval of 3 months between doses. Adolescents (≥13 years of age) and Adults: 2 doses, to be administered with a minimum interval of 4 weeks between doses.
M-M-R®II:
The dose for any age is approximately 0.5 mL administered intramuscularly or subcutaneously.
The recommended age for primary vaccination is 12 to 15 months and the second dose should be given at 4 to 6 years of age.
Before administrating VARIVAX® (Varicella Virus Vaccine Live), M-M-R®II (Measles, Mumps, and Rubella Virus Vaccine Live), or ProQuad® (Measles, Mumps, Rubella and Varicella Virus Vaccine Live), please read the Prescribing Information. The Patient Information also is available for VARIVAX, M-M-R®II, and ProQuad.
About Merck
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.
Source: Merck & Co., Inc.
FDA approves intramuscular administration for Merck’s MMRV family of vaccines
Mar. 06, 2023 6:56 AM ET
By: Mamta Mayani, SA News Editor
- Merck (NYSE:MRK) announces that the FDA has approved the addition of the intramuscular (IM) route of administration to the United States Product Insert (USPI) for Merck’s MMRV family of vaccines: M-M-RII, VARIVAX, and ProQuad.
- Until now these vaccines have only been administ
- https://seekingalpha.com/news/3944331-fda-approves-intramuscular-administration-for-mercks-mmrv-family-of-vaccines
- Merck & Co., Inc. (MRK)
- https://www.merckvaccines.com/
Temferon
MMRV Family of Vaccines -ProQuad, M-M-R®II, and VARIVAX
Temferon
FDA Grants Orphan Drug Designation to Temferon for Treatment of Glioblastoma Multiforme
Mar 02, 2023
MILAN and NEW YORK, March 02, 2023 (GLOBE NEWSWIRE) -- Genenta Science (NASDAQ: GNTA), a clinical-stage immuno-oncology company developing a cell-based platform harnessing the power of hematopoietic stem cells to provide durable and safe treatments for solid tumors, today announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to Temferon™ for the treatment of glioblastoma multiforme (GBM).
"We expect that the FDA’s decision to grant Orphan Drug Designation to Temferon will enhance the development of our cell therapy, which we believe has the potential to address the unmet medical need of patients and strengthen our clinical program," said Pierluigi Paracchi, Chief Executive Officer of Genenta. "The Orphan Drug Designation program highlights the significant need for an efficacious therapy for patients suffering from glioblastoma multiforme."
Temferon is a proprietary cell therapy designed to reprogram the tumor microenvironment by delivering immunomodulatory molecules directly to tumors. Genenta is testing Temferon in an ongoing Phase 1/2a clinical trial in newly diagnosed patients with GBM who have an unmethylated MGMT gene promoter (uMGMT-GBM).
GBM is the most common malignant primary brain tumor and the most aggressive diffuse glioma, with unmethylated MGMT promoter status identified in approximately 60% of the GBM population.
The ODD program supports the development of treatments that address diseases affecting fewer than 200,000 people in the United States (which equates to approximately 6 cases per 10,000 population). Incentives that come with the designation include eligibility for federal grants, tax credits for qualified clinical trials, prescription drug user fee exemptions, and a seven-year marketing exclusivity period upon FDA approval.
About Genenta Science
Genenta (www.genenta.com) is a clinical-stage biotechnology company engaged in the development of a proprietary hematopoietic stem cell gene therapy for the treatment of a variety of solid tumor cancers. Temferon™ is based on ex-vivo gene transfer into autologous Tie2+ hematopoietic stem/progenitor cells (HSPCs) to deliver immunomodulatory molecules directly via tumor-infiltrating monocytes/macrophages (Tie2 Expressing Monocytes - TEMs). Temferon™, which is under investigation in a phase 1/2a clinical trial in newly diagnosed Glioblastoma Multiforme patients who have an unmethylated MGMT gene promoter (uMGMT-GBM), is designed to reach solid tumors, induce a durable immune response not restricted to pre-selected tumor antigens nor type, and avoid systemic toxicity, which are some of the main unresolved challenges in immuno-oncology.
Source: Genenta Science
Genenta's brain cancer cell therapy gets FDA orphan drug status
Mar. 02, 2023 7:04 AM ET
By: Ravikash, SA News Editor
- The U.S. Food and Drug Administration (FDA) granted orphan drug designation (ODD) to Genenta Science's (NASDAQ:GNTA) to Temferon to treat glioblastoma multiforme (GBM), a type of brain cancer.
- https://seekingalpha.com/news/3943156-genenta-brain-cancer-cell-therapy-gets-fda-orphan-drug-status
- Genenta Science S.p.A. (GNTA)
- https://www.genenta.com/our-pipeline/
ADX-2191
MMRV Family of Vaccines -ProQuad, M-M-R®II, and VARIVAX
Temferon
FDA Accepts for Priority Review ADX-2191 New Drug Application for the Treatment of Primary Vitreoretinal Lymphoma
March 2, 2023
PDUFA Date is June 21, 2023
Planned U.S. Launch of ADX-2191 in Second Half of 2023, Pending Approval by the FDA
ADX-2191 with Potential to be the First FDA-Approved Drug Available for Patients Suffering from Primary Vitreoretinal Lymphoma
LEXINGTON, Mass.--(BUSINESS WIRE)--Mar. 2, 2023-- Aldeyra Therapeutics, Inc. (Nasdaq: ALDX) (Aldeyra) today announced that the U.S. Food and Drug Administration (FDA) accepted for Priority Review the New Drug Application (NDA) for ADX-2191 (methotrexate injection, USP), an investigational drug candidate, for the treatment of primary vitreoretinal lymphoma. The FDA assigned a Prescription Drug User Fee Act (PDUFA) date of June 21, 2023. The FDA noted that no potential filing review issues have been identified.
“The FDA’s decision to grant Priority Review with a PDUFA date four months from NDA acceptance underscores the significant need for an FDA-approved treatment of primary vitreoretinal lymphoma, a rare but potentially fatal cancer,” stated Todd C. Brady, M.D., Ph.D., Aldeyra’s President and Chief Executive Officer. “We are working closely with the FDA during the review process to bring ADX‑2191 to patients as quickly as possible, and plan to launch ADX-2191 in the United States in the second half of this year, pending approval by the FDA.”
The NDA submission is supported by a combination of more than three decades of published literature on the safety and efficacy of methotrexate, the active ingredient of ADX‑2191, for the treatment of primary vitreoretinal lymphoma, in addition to safety data from the recently completed Phase 3 GUARD Trial of ADX-2191 in patients with proliferative vitreoretinopathy. During the Phase 3 GUARD Trial, no safety signals were observed, and ADX-2191 was well tolerated; there were no observed treatment-emergent serious adverse events. The most common adverse event associated with ADX‑2191 treatment was punctate keratitis, a frequently observed side effect of intravitreal methotrexate, that was most commonly mild in severity.
About ADX-2191
ADX-2191 (methotrexate injection, USP) is a sterile, non-compounded intravitreal formulation of methotrexate for the potential prevention or treatment of specific rare retinal diseases, including primary vitreoretinal lymphoma, proliferative vitreoretinopathy, and retinitis pigmentosa. The ADX-2191 intravitreal formulation is preservative-free, is designed to be vitreous-compatible, and is optimized for excipient composition, viscosity, density, tonicity, pH, concentration, and volume of administration. ADX-2191 has received FDA Orphan Drug Designation for the prevention of proliferative vitreoretinopathy, and for the treatment of primary vitreoretinal lymphoma and retinitis pigmentosa.
About Primary Vitreoretinal Lymphoma
Primary vitreoretinal lymphoma is a rare, aggressive, and potentially fatal retinal cancer that is diagnosed in approximately 300 to 600 patients in the United States per year. The median survival for newly diagnosed patients is less than five years. No approved treatments are currently available, though intravitreal injection of compounded methotrexate represents the current standard of care.
About Aldeyra
Aldeyra Therapeutics is a clinical-stage biotechnology company developing innovative therapies designed to treat immune-mediated diseases. Our approach is to discover and develop pharmaceuticals that modulate immunological systems, instead of directly inhibiting or activating single protein targets, with the goal of optimizing multiple pathways at once while minimizing toxicity. Our product candidates include RASP (reactive aldehyde species) modulators ADX-629, ADX-246, ADX-248, and chemically related molecules for the potential treatment of systemic and retinal immune-mediated diseases. Our pre-commercial product candidates are reproxalap, a RASP modulator for the potential treatment of dry eye disease (under U.S. Food and Drug Administration New Drug Application review) and allergic conjunctivitis, and ADX-2191, a novel formulation of intravitreal methotrexate for the potential treatment of primary vitreoretinal lymphoma (under U.S. Food and Drug Administration New Drug Application review), proliferative vitreoretinopathy, and other rare sight-threatening retinal diseases. For more information, visit https://www.aldeyra.com/ and follow us on LinkedIn, Facebook, and Twitter.
View source version on businesswire.com: https://www.businesswire.com/news/home/20230301005873/en/
Source: Aldeyra Therapeutics, Inc.
FDA accepts for priority review Aldeyra's ADX-2191 application in retinal cancer
Mar. 02, 2023 7:27 AM ET
Aldeyra Therapeutics, Inc. (ALDX)
By: Mamta Mayani, SA News Editor
- Under Priority Review, the FDA has accepted Aldeyra Therapeutics' (NASDAQ:ALDX) New Drug Application (NDA) for ADX-2191 (methotrexate injection, USP), an investigational drug candidate, for the treatment of primary vitreoretinal lymphoma.
- https://seekingalpha.com/news/3943183-fda-accepts-for-priority-review-aldeyras-adx-2191-application-in-retinal-cancer
- Aldeyra Therapeutics, Inc. (ALDX)
- https://www.aldeyra.com/pipeline-disease-areas/
Milvexian
NUBEQA® (darolutamide)
Batiraxcept
The Bristol Myers Squibb-Janssen Collaboration Launches Pivotal Phase 3 Librexia Clinical Trial Program Evaluating Milvexian, an Investigational Oral Factor XIa Inhibitor
03/02/2023CATEGORY:
The Librexia program is the most comprehensive Factor XIa Phase 3 clinical development program, and will provide indispensable data from nearly 50,000 patients across three simultaneous trials including Librexia STROKE, Librexia ACS and Librexia AF
First patient has been enrolled in Librexia STROKE trial
PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) in collaboration with Janssen Pharmaceuticals, Inc., one of the Janssen Pharmaceutical Companies of Johnson and Johnson (Janssen) today announced the launch of the Phase 3 Librexia program studying milvexian, an investigational oral factor XIa (FXIa) inhibitor (antithrombotic).
The Librexia program is unrivaled as the most comprehensive FXIa development program to date and will provide important data from nearly 50,000 patients across three indication-seeking studies: Librexia STROKE, Librexia ACS and Librexia AF. Enrollment has begun for the Librexia STROKE trial, which is evaluating milvexian in addition to standard of care antiplatelet therapy for stroke prevention in patients after an acute ischemic stroke or high-risk transient ischemic attack. The Librexia ACS trial, which will evaluate event reduction in acute coronary syndromes in addition to standard of care antiplatelet therapy, and the Librexia AF trial, which will investigate milvexian compared to apixaban in the prevention of stroke in patients with atrial fibrillation, will also initiate during the first half of 2023.
“The depth and breadth of the Librexia clinical development program will capture data in three related but distinct areas of clinical need related to residual risk of thrombotic events and patient bleeding, and evaluate milvexian’s potential to advance beyond the current standard of care and improve patient outcomes in acute coronary syndromes, atrial fibrillation and ischemic stroke,” said Robert Harrington, M.D., Arthur L. Bloomfield professor of medicine and chair of the Department of Medicine, Stanford University, Librexia program chair. “A novel treatment that enhances the benefit-risk profile will be a clinically meaningful and welcomed advance in the treatment of these conditions.”
Important Phase 2 proof-of-concept data for milvexian demonstrated a differentiated antithrombotic profile as both a monotherapy and in combination with antiplatelet therapy. This included data in patients with ischemic stroke or high-risk transient ischemic attack that may suggest a compelling benefit-risk profile, ultimately enabling the initiation of the Librexia program this year.
“The Librexia program is a first-of-its-kind clinical program, with three Phase 3 trials running concurrently that aim to investigate whether milvexian can improve the benefit-risk profile in thrombotic care by delivering reduced thrombotic events with less bleeding for more patients in need,” said Roland Chen, M.D., senior vice president and head, Cardiovascular Development, Global Drug Development, Bristol Myers Squibb. “BMS and Janssen bring deep heritage and expertise in cardiovascular care to this program, in partnership with renowned experts, and we look forward to continuing to evaluate the potential of milvexian to address key unmet medical needs for patients living with thrombotic diseases.”
The Librexia STROKE trial is an event-driven registrational trial powered to show superiority in reducing the risk of stroke/ischemic events on top of standard of care antiplatelet therapy. Librexia ACS and Librexia AF trials are expected to begin enrolling within the first half of 2023. More information on the Librexia STROKE trial can be found on http://www.clinicaltrials.gov (NCT05702034).
About Milvexian*
Milvexian is an investigational, oral factor XIa (FXIa) inhibitor (antithrombotic) being studied for the prevention and treatment of major thrombotic conditions as part of the Librexia program, the most comprehensive FXIa clinical development program today.
*Milvexian is an investigational agent and has not been approved for use in any country, for any indication.
About the Librexia Program
The Librexia program is the most comprehensive and unrivaled FXIa clinical development program today, studying nearly 50,000 patients across three concurrent clinical trials (Librexia STROKE, Librexia ACS and Librexia AF). Grounded in strong Phase 2 efficacy and safety data, the Librexia program aims to investigate whether milvexian can enhance the benefit-risk profile associated with treating patients with these three conditions by delivering reduced thrombotic events with no increased risk of bleeding. The program is designed and powered for success to potentially advance beyond the standard of care and help improve outcomes in a wide range of patients with thrombotic diseases.
About Librexia STROKE
Librexia STROKE is a Phase 3, randomized, double-blind, parallel-group, placebo-controlled study to demonstrate the efficacy and safety of milvexian in addition to single or dual antiplatelet therapy for stroke prevention after an acute ischemic stroke or high-risk transient ischemic attack (TIA). More information can be found on http://www.clinicaltrials.gov (NCT05702034).
About Librexia ACS
Librexia ACS is a randomized, double-blind, placebo-controlled, event-driven study to demonstrate the efficacy and safety of milvexian after a recent acute coronary syndrome.
AboutLibrexia AF
Librexia AF is a randomized, double-blind, double-dummy, parallel group, active-controlled study to evaluate the efficacy and safety of milvexian versus apixaban in participants with atrial fibrillation.
About AXIOMATIC-SSP and AXIOMATIC-TKR
The milvexian Phase 2 clinical trial program consisted of two Phase 2 studies: AXIOMATIC-TKR, a randomized, open-label, parallel-group, dose-ranging multicenter study that evaluated the efficacy and safety of milvexian versus subcutaneous enoxaparin in patients undergoing elective total knee replacement (TKR) surgery, and AXIOMATIC-SSP, a Phase 2, global, randomized, double-blind, placebo-controlled, dose-ranging study that evaluated the efficacy and safety of milvexian for the prevention of new symptomatic ischemic stroke or new covert brain infarction in patients receiving aspirin and clopidogrel following acute ischemic stroke or transient ischemic attack (TIA).
A total of 3,608 patients were enrolled across both studies. More information can be found on http://www.clinicaltrials.gov (NCT03766581, NCT03891524).
About the Bristol Myers Squibb-Janssen Collaboration
Bristol Myers Squibb and the Janssen Pharmaceutical Companies of Johnson & Johnson (Janssen),two unsurpassed leaders in cardiovascular care, are determined to close the gap in unmet needs in thrombosis management by overcoming the limits of today’s treatments. The collaboration to develop and commercialize milvexian aims to leverage the combined scientific heritage and world-class commercial capabilities of each company, all in service of improved patient outcomes. The collaboration is uniquely equipped to deliver on the promise of FXIa inhibitors and is working diligently to ensure cutting-edge safe and effective treatment options are available for patients.
About Bristol Myers Squibb
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.
Source: Bristol Myers Squibb
Bristol Myers, Janssen launch late-stage Librexia program evaluating milvexian
Mar. 02, 2023 8:01 AM ET
Bristol-Myers Squibb Company (BMY)JNJ
By: Mamta Mayani, SA News Editor
- Bristol Myers Squibb (NYSE:BMY) in collaboration with Janssen Pharmaceuticals, a Johnson and Johnson (JNJ) company announces the launch of Phase 3 Librexia program studying milvexian, an investigational oral factor XIa (FXIa) inhibitor (antithrombotic).
- https://seekingalpha.com/news/3943202-bristol-myers-janssen-launch-late-stage-librexia-program-evaluating-milvexian
- Bristol-Myers Squibb Company (BMY)JNJ
- https://www.janssen.com/
- https://www.bms.com/
Batiraxcept
NUBEQA® (darolutamide)
Batiraxcept
Feb 28, 2023
Aravive Announces FDA Orphan Drug Designation Granted to Batiraxcept for the Treatment of Pancreatic Cancer
- Dose escalation portion of ongoing Phase 1b/2 pancreatic adenocarcinoma trial initiated, with preliminary results expected in 2H 2023
HOUSTON, Feb. 28, 2023 (GLOBE NEWSWIRE) -- Aravive, Inc. (Nasdaq: ARAV, “the Company”), a late clinical-stage oncology company developing targeted therapeutics to treat metastatic disease, today announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to batiraxcept for the treatment of pancreatic ductal adenocarcinoma cancer (PDAC).
The FDA’s Office of Orphan Products Development grants ODD status to a drug or biological product to prevent, diagnose or treat a rare disease or condition affecting fewer than 200,000 people in the USA. Companies that are granted ODD are eligible for incentives, including tax credits for qualified clinical trials, exemption from user fees and up to seven years of market exclusivity after approval.
“Receiving Orphan Drug Designation is another important milestone for batiraxcept, and it underscores the significant unmet medical need in patients with pancreatic cancer, typically diagnosed at an incurable advanced stage with a 5-year survival rate of 11%1,” said Gail McIntyre, Ph.D., DABT, Chief Executive Officer of Aravive. “Three patients from our P1b trial are still responding to treatment with 15mg/kg batiraxcept, gemcitabine and nab-paclitaxel after 1 year and one patient has a confirmed complete response. Consistent with our other clinical trials, we noted a relationship between clinical activity and batiraxcept drug levels, however highly fibrotic tumors like PDAC may require more batiraxcept than platinum-resistant ovarian cancer and clear cell renal cell cancer patients to reach the appropriate batiraxcept drug levels. Due to this characteristic of pancreatic cancer, we are testing higher doses of batiraxcept to see if we can increase the proportion of patients who benefit from the triplet regimen.”
Batiraxcept (15mg/kg on Days 1 & 15) is currently being evaluated in a Phase 1b/2 trial (NCT04983407) as first-line treatment in combination with gemcitabine (1000 mg/m2 on Days 1, 8, & 15) and nab-paclitaxel (125 mg/m2 on Days 1, 8, & 15) in patients with locally advanced (nonresectable Stage II or Stage III) or metastatic (Stage IV) pancreatic adenocarcinoma. The Phase 1b portion of the trial is ongoing and the dose escalation phase was initiated this month. Preliminary results from the 20mg/kg batiraxcept plus gemcitabine and nab-paclitaxel cohort are anticipated in the second half of 2023. In addition to ODD granted by the FDA in pancreatic cancer, batiraxcept was previously granted ODD by the European Commission in platinum resistant recurrent ovarian cancer (PROC) and was granted Fast Track Designation by the FDA in PROC and clear cell renal cell carcinoma (ccRCC).
About Aravive
Aravive, Inc. is a late clinical-stage oncology company developing targeted therapeutics to treat metastatic disease. Batiraxcept (formerly AVB-500), is an ultra-high affinity decoy protein that binds to GAS6, the sole ligand that activates AXL, thereby inhibiting metastasis and tumor growth, and restoring sensitivity to anti-cancer agents. Batiraxcept has been granted Fast Track Designation by the U.S. FDA for both clear cell renal cell carcinoma and platinum-resistant ovarian cancer and Orphan Drug Designation by the European Commission in platinum resistant recurrent ovarian cancer. Batiraxcept is in an active registrational Phase 3 trial in platinum resistant ovarian cancer (NCT04729608), a Phase 1b/2 trial in clear cell renal cell carcinoma (NCT04300140), and a Phase 1b/2 trial in pancreatic adenocarcinoma (NCT04983407). The Company is based in Houston, Texas and received a Product Development Award from the Cancer Prevention & Research Institute of Texas (CPRIT) in 2016. Additional information at www.aravive.com.
Aravive stock pops on FDA orphan drug status for batiraxcept to treat pancreatic cancer
Mar. 01, 2023 5:01 AM ET
By: Ravikash, SA News Editor
- The U.S. Food and Drug Administration (FDA) granted orphan drug designation (ODD) to Aravive's (NASDAQ:ARAV) batiraxcept to treat pancreatic ductal adenocarcinoma cancer (PDAC).
- https://seekingalpha.com/news/3942389-aravive-stock-pops-on-fda-orphan-drug-status-for-batiraxcept-to-treat-pancreatic-cancer
- Aravive, Inc. (ARAV)
- https://aravive.com/
- https://aravive.com/pipeline/
NUBEQA® (darolutamide)
NUBEQA® (darolutamide)
LEQEMBI™ (lecanemab-irmb) injection
3/1/2023
Darolutamide receives EU approval for additional indication in prostate cancer
Darolutamide receives EU approval for additional indication in prostate cancer
ORION CORPORATION
PRESS RELEASE
1 March 2023 at 13:00 EET
Darolutamide receives EU approval for additional indication in prostate cancer
- European Commission granted approval of darolutamide for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC)
- Approval is based on Phase III ARASENS trial data
The European Commission has granted marketing authorisation in the European Union (EU) for darolutamide, an oral androgen receptor inhibitor (ARi), plus androgen deprivation therapy (ADT) in combination with docetaxel, for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC). Darolutamide is already approved under the brand name Nubeqa® for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC), who are at high risk of developing metastatic disease.
The EU approval is based on the positive results from the Phase III ARASENS trial, which demonstrated that darolutamide plus ADT in combination with docetaxel significantly reduced the risk of death by 32.5% compared to ADT with docetaxel, in patients with mHSPC. Additionally, the darolutamide combination showed consistent benefits across clinically relevant secondary endpoints, with the overall incidence of treatment-emergent adverse events being similar between treatment arms.
Prostate cancer is the most commonly diagnosed cancer in men in almost all northern and western European countries.1 Only 30% of men with mHSPC will survive five years or more after diagnosis.2 Most men with mHSPC eventually progress to metastatic castration-resistant prostate cancer (mCRPC), a condition with limited long-term survival.3,4
Darolutamide is being investigated in a broad development program with an additional three ongoing or planned large clinical studies, to investigate its potential across prostate cancer patients from the early- to the late-stage of this disease. This includes the ARANOTE Phase III trial evaluating darolutamide and ADT versus ADT alone for mHSPC.
Darolutamide is developed jointly by Orion and Bayer. Bayer is responsible for global commercialization, with co-promotion from Bayer and Orion in certain European markets, e.g. France, Germany, Italy, Spain, the UK, Scandinavia and Finland.
About the ARASENS Trial
The ARASENS trial is a randomized, Phase III, multi-center, double-blind, placebo-controlled trial which was prospectively designed to investigate the efficacy and safety of oral darolutamide, an androgen receptor inhibitor (ARi), plus androgen deprivation therapy (ADT) and the chemotherapy docetaxel in patients with metastatic hormone-sensitive prostate cancer (mHSPC). A total of 1,306 newly diagnosed patients were randomized in a 1:1 ratio to receive 600 mg of darolutamide twice a day or matching placebo, plus ADT and docetaxel.
The primary endpoint of this trial was overall survival (OS). Secondary endpoints included time to castration-resistant prostate cancer (CRPC), time to pain progression, time to first symptomatic skeletal event (SSE), time to initiation of subsequent anticancer therapy, all measured at 12‐week intervals, as well as adverse events (AEs) as a measure of safety and tolerability. Results from this trial were published in the New England Journal of Medicine.5 The ARASENS trial demonstrated that darolutamide plus androgen deprivation therapy (ADT) and docetaxel significantly reduced the risk of death by 32.5% compared to ADT plus docetaxel.5 Improvements in the secondary endpoints supported the benefit observed in the primary endpoint, overall survival.5
About Metastatic Hormone-Sensitive Prostate Cancer
Prostate cancer is the second most commonly diagnosed malignancy in men worldwide. In 2020, an estimated 1.4 million men were diagnosed with prostate cancer, and about 375,000 died from the disease worldwide.6
At the time of diagnosis, most men have localized prostate cancer, meaning their cancer is confined to the prostate gland and can be treated with curative surgery or radiotherapy. Upon relapse, when the disease will metastasise or spread, or if the disease is newly diagnosed, but has already spread, the disease is hormone-sensitive and androgen deprivation therapy (ADT) is the cornerstone of treatment for this hormone-sensitive disease. Current treatment options for men with metastatic hormone-sensitive prostate cancer (mHSPC) include hormone therapy, such as ADT, androgen receptor pathway inhibitors plus ADT or a combination of docetaxel chemotherapy and ADT. Despite these treatments, a large proportion of men with mHSPC will eventually experience progression to metastatic castration-resistant prostate cancer (mCRPC), a condition with limited survival.
About darolutamide
Darolutamide is an oral androgen receptor inhibitor (ARi) with a distinct chemical structure that binds to the receptor with high affinity and exhibits strong antagonistic activity, thereby inhibiting the receptor function and the growth of prostate cancer cells. The low potential for blood-brain barrier penetration for darolutamide is supported by preclinical models and neuroimaging data in healthy humans. This is supported by the overall low incidence of central nervous system (CNS)-related adverse events (AEs) compared to placebo as seen in the ARAMIS Phase III trial7 and the maintained verbal learning and memory observed in the darolutamide arm of the Phase II ODENZA trial.8
The product is approved under the brand name Nubeqa® in more than 80 countries around the world, including the U.S., EU, Japan and China, for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC), who are at high risk of developing metastatic disease. It is also approved for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC) in a number of markets including the U.S. and Japan. Filings in other regions are underway or planned by Bayer. The compound is also being investigated in further studies across various stages of prostate cancer, including in the ARANOTE Phase III trial evaluating darolutamide plus androgen deprivation therapy (ADT) versus ADT alone for metastatic hormone-sensitive prostate cancer (mHSPC), as well as the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) led international Phase III co-operative group DASL-HiCaP (ANZUP1801) trial evaluating darolutamide as an adjuvant treatment for localised prostate cancer with very high risk of recurrence. Information about these trials can be found at www.clinicaltrials.gov. In addition, a study to explore the potential of darolutamide in the early setting for patients who have experienced a rise in their prostate specific antigen (PSA) levels following surgery or radiation, is also planned.
Orion wins EU approval for darolutamide for additional indication in prostate cancer
Mar. 01, 2023 7:15 AM ET
By: Mamta Mayani, SA News Editor
The European Commission has granted marketing authorization in the European Union (EU) for Orion's (OTCPK:ORINY) darolutamide, an oral androgen receptor inhibitor (ARi), plus androgen deprivation therapy (ADT) in combination with docetaxel, for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC).
LEQEMBI™ (lecanemab-irmb) injection
Nirogacestat (Gamma Secretase Inhibitor)
LEQEMBI™ (lecanemab-irmb) injection
Biologics License Application for Lecanemab Designated for Priority Review by China National Medical Products Administration
FEBRUARY 27, 2023 • NEWS RELEASE
TOKYO and CAMBRIDGE, Mass., Feb. 27, 2023 (GLOBE NEWSWIRE) -- Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") and Biogen Inc. (Nasdaq: BIIB, Corporate headquarters: Cambridge, Massachusetts, CEO: Christopher A. Viehbacher, "Biogen") announced today that the Biologics License Application (BLA) for lecanemab (brand name in the U.S.: LEQEMBI™), an investigational anti-amyloid beta (Aβ) protofibril antibody, has been designated for Priority Review by the National Medical Products Administration (NMPA) in China. The Priority Review and Approval Procedure was implemented by the NMPA with the aim of accelerating research, development and launch of new medicines that have significant clinical value. Under this Procedure, the assessment period is expected to be shortened.
In China, Eisai initiated submission of data for the BLA to the NMPA in December 2022. Eisai initially submitted a package that includes data from the Phase II clinical trial (Study 201) and the top-line data of the large global Phase III Clarity AD study in mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) and mild AD (collectively known as early AD) with confirmed Aβ accumulation in the brain. Eisai will submit additional data including full data of the Clarity AD study, as directed by the NMPA.
Lecanemab selectively binds and eliminates soluble, toxic Aβ aggregates (protofibrils) that are thought to contribute to the neurotoxicity in AD. As such, lecanemab may have the potential to have an effect on disease pathology and to slow down the progression of the disease. The Clarity AD study of lecanemab met its primary endpoint and all key secondary endpoints with highly statistically significant results. In November 2022, the results of the Clarity AD study were presented at the 2022 Clinical Trials on Alzheimer’s Disease (CTAD) conference, and simultaneously published in the New England Journal of Medicine, a peer-reviewed medical journal.
In the U.S., lecanemab was granted accelerated approval by the U.S. Food and Drug Administration (FDA) on January 6, 2023. On the same day, Eisai submitted a supplemental Biologics License Application (sBLA) to the FDA for approval under the traditional pathway. In Europe, Eisai submitted a marketing authorization application (MAA) to the European Medicines Agency (EMA) on January 9, 2023, which was accepted on January 26, 2023. In Japan, Eisai submitted a marketing authorization application to the Pharmaceuticals and Medical Devices Agency (PMDA) on January 16, 2023, and Priority Review was designated by the Ministry of Health, Labour and Welfare (MHLW) on January 26, 2023.
Eisai serves as the lead of lecanemab development and regulatory submissions globally with both Eisai and Biogen co-commercializing and co-promoting the product and Eisai having final decision-making authority.
1. About Priority Review and Approval Procedure in China
The Priority Review and Approval Procedure was implemented by the National Medical Products Administration (NMPA) with the aim of accelerating research, development and launch of new medicines that have significant clinical value. Under this Procedure, the assessment period is expected to be shortened. There are six categories of priority review designations as follows and lecanemab was designated as Category 1: 1) Innovative new drugs and new dosage forms for the prevention and treatment of serious infectious diseases and rare diseases for which there is an urgent clinical need. 2) Drugs with additional indications and new dosage forms that are compatible with the physiological characteristics of children. 3) Vaccines and innovative vaccines that are urgently needed to prevent or control disease. 4) Drugs designated as breakthrough therapies. 5) Medicinal products that are reviewed under the conditional approval procedure. 6) Other drugs designated by NMPA for priority review.
2. About Lecanemab
Lecanemab (Brand Name in the U.S.: LEQEMBI™) is the result of a strategic research alliance between Eisai and BioArctic. Lecanemab is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble (protofibril) and insoluble forms of amyloid-beta (Aβ). In the U.S., LEQEMBI was granted accelerated approval by the U.S. Food and Drug Administration (FDA) on January 6, 2023. LEQEMBI is indicated for the treatment of Alzheimer’s disease (AD) in the U.S. Treatment with LEQEMBI should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. There are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied. This indication is approved under accelerated approval based on reduction in Aβ plaques observed in patients treated with LEQEMBI. Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial.
Please see full Prescribing Information.
Eisai has completed lecanemab subcutaneous bioavailability study, and subcutaneous dosing is currently being evaluated in the Clarity AD (Study 301) OLE.
Since July 2020 the Phase 3 clinical study (AHEAD 3-45) for individuals with preclinical AD, meaning they are clinically normal and have intermediate or elevated levels of amyloid in their brains, is ongoing. AHEAD 3-45 is conducted as a public-private partnership between the Alzheimer’s Clinical Trial Consortium that provides the infrastructure for academic clinical trials in AD and related dementias in the U.S, funded by the National Institute on Aging, part of the National Institutes of Health, Eisai and Biogen.
Since January 2022, the Tau NexGen clinical study for Dominantly Inherited AD (DIAD), that is conducted by Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU), led by Washington University School of Medicine in St. Louis, is ongoing.
3. About the Collaboration between Eisai and Biogen for AD
Eisai and Biogen have been collaborating on the joint development and commercialization of AD treatments since 2014. Eisai serves as the lead of lecanemab development and regulatory submissions globally with both companies co-commercializing and co-promoting the product and Eisai having final decision-making authority.
4. About the Collaboration between Eisai and BioArctic for AD
Since 2005, Eisai and BioArctic have had a long-term collaboration regarding the development and commercialization of AD treatments. Eisai obtained the global rights to study, develop, manufacture and market lecanemab for the treatment of AD pursuant to an agreement with BioArctic in December 2007. The development and commercialization agreement on the antibody lecanemab back-up was signed in May 2015.
5. About Eisai Co., Ltd.
Eisai’s Corporate Concept is “to give first thought to patients and people in the daily living domain, and to increase the benefits that health care provides.” Under this Concept (also known as human health care (hhc) Concept), we aim to effectively achieve social good in the form of relieving anxiety over health and reducing health disparities. With a global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to create and deliver innovative products to target diseases with high unmet medical needs, with a particular focus in our strategic areas of Neurology and Oncology.
In addition, we demonstrate our commitment to the elimination of neglected tropical diseases (NTDs), which is a target (3.3) of the United Nations Sustainable Development Goals (SDGs), with working on various activities together with global partners.
For more information about Eisai, please visit www.eisai.com (for global headquarters: Eisai Co., Ltd.), and connect with us on Twitter @Eisai_SDGs.
6. About Biogen
Founded in 1978, Biogen is a leading global biotechnology company that has pioneered multiple breakthrough innovations including a broad portfolio of medicines to treat multiple sclerosis, the first approved treatment for spinal muscular atrophy, and two co-developed treatments to address a defining pathology of Alzheimer’s disease. Biogen is advancing a pipeline of potential novel therapies across neurology, neuropsychiatry, specialized immunology and rare diseases and remains acutely focused on its purpose of serving humanity through science while advancing a healthier, more sustainable and equitable world.
The company routinely posts information that may be important to investors on its website at www.biogen.com. Follow Biogen on social media – Twitter, LinkedIn, Facebook, YouTube.
Biogen, Eisai's Alzheimer's therapy lecanemab gets priority review in Chinna
Feb. 28, 2023 4:32 AM ET
Biogen Inc. (BIIB), ESALFBRCTF
By: Ravikash, SA News Editor
China's National Medical Products Administration (NMPA) granted priority review to Biogen (NASDAQ:BIIB) and Eisai's (OTCPK:ESALF) application seeking approval of Alzheimer's disease (AD) therapy lecanemab.
https://us.eisai.com/eisai_leqembi_now_approved
https://www.leqembi.com/-/media/Files/Leqembi/Prescribing-Information.pdf
Nirogacestat (Gamma Secretase Inhibitor)
Nirogacestat (Gamma Secretase Inhibitor)
Nirogacestat (Gamma Secretase Inhibitor)
SpringWorks Therapeutics Announces FDA Acceptance and Priority Review of New Drug Application for Nirogacestat for the Treatment of Adults with Desmoid Tumors
February 27, 2023PDF Version
– PDUFA Action Date Set for August 27, 2023 –
STAMFORD, Conn., Feb. 27, 2023 (GLOBE NEWSWIRE) -- SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a clinical-stage biopharmaceutical company focused on developing life-changing medicines for patients with severe rare diseases and cancer, announced today that the U.S. Food and Drug Administration (FDA) has accepted the Company’s New Drug Application (NDA) for nirogacestat, an investigational gamma secretase inhibitor, for the treatment of adults with desmoid tumors. The NDA was granted Priority Review and has been given a Prescription Drug User Fee Act (PDUFA) action date of August 27, 2023. The FDA’s Priority Review designation is given to investigational medicines that treat a serious condition and offer significant improvements in safety or effectiveness. In addition, the FDA has stated that it is not currently planning to hold an advisory committee meeting to discuss the application.
"People with desmoid tumors can experience severe pain and other debilitating morbidities, and we are excited by the opportunity to potentially transform the standard of care for these patients,” said Saqib Islam, Chief Executive Officer of SpringWorks. "The acceptance of our NDA for nirogacestat with Priority Review represents a significant milestone in our ambition to provide the first approved therapy for patients with desmoid tumors. We look forward to working closely with the FDA during the review process and remain focused on ensuring that we are well-positioned to expeditiously serve the desmoid tumor patient and the physician communities following approval."
The NDA is being reviewed under the FDA’s Real-Time Oncology Review (RTOR) program and is based on the previously announced positive results from the Phase 3 DeFi trial, a global, randomized, double-blind, placebo-controlled trial evaluating nirogacestat in adult patients with desmoid tumors. The FDA granted Fast Track and Breakthrough Therapy designations to nirogacestat for the treatment of adult patients with progressive, unresectable, recurrent or refractory desmoid tumors or deep fibromatosis. Nirogacestat has also received Orphan Drug designation from the FDA for the treatment of desmoid tumors.
About the DeFi Trial
DeFi (NCT03785964) is a global, randomized (1:1), double-blind, placebo-controlled Phase 3 trial evaluating the efficacy, safety and tolerability of nirogacestat in adult patients with progressing desmoid tumors. The double-blind phase of the study randomized 142 patients (nirogacestat, n=70; placebo n=72) to receive 150 mg of nirogacestat or placebo twice daily. Key eligibility criteria included tumor progression by ≥20% as measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) within 12 months prior to screening. The primary endpoint was progression-free survival, as assessed by blinded independent central review, or death by any cause. Secondary and exploratory endpoints included safety and tolerability measures, objective response rate (ORR), duration of response, changes in tumor volume assessed by magnetic resonance imaging (MRI), and changes in patient-reported outcomes (PROs). DeFi includes an open-label extension phase, which is ongoing.
About Desmoid Tumors
Desmoid tumors are rare, aggressive, locally invasive, and potentially morbid tumors of the soft tissues.1,2 While they do not metastasize, desmoid tumors are associated with a high rate of recurrence.2,3,4 Sometimes referred to as aggressive fibromatosis, or desmoid fibromatosis, these soft tissue tumors can be serious, debilitating, and, in rare cases when vital structures are impacted, they can be life-threatening.2,5
Desmoid tumors are most commonly diagnosed in patients between the ages of 20 and 44 years, with a two-to-three times higher prevalence in females.4,6,7,8 It is estimated that there are 1,000-1,650 new cases diagnosed per year in the United States.7,8,9
Historically, desmoid tumors were treated with surgical resection, but this approach has become less favored due to a high recurrence rate after surgery.1,4,10 There are currently no FDA-approved therapies for the treatment of desmoid tumors.
About Nirogacestat
Nirogacestat is an oral, selective, small molecule gamma secretase inhibitor in Phase 3 clinical development for desmoid tumors and in Phase 2 clinical development for ovarian granulosa cell tumors. Nirogacestat is an investigational drug for which safety and efficacy have not been established.
Gamma secretase cleaves multiple transmembrane protein complexes, including Notch, which is believed to play a role in activating pathways that contribute to growth of desmoid and ovarian granulosa cell tumors. Gamma secretase has also been shown to directly cleave membrane-bound B cell maturation antigen (BCMA), resulting in the release of the BCMA extracellular domain (ECD) from the cell surface. By inhibiting gamma secretase, membrane-bound BCMA can be preserved, increasing target density while reducing levels of soluble BCMA ECD, which may serve as decoy receptors for BCMA-directed therapies. Nirogacestat’s ability to enhance the activity of BCMA-directed therapies has been observed in preclinical models of multiple myeloma. SpringWorks is evaluating nirogacestat as a BCMA potentiator and has several collaborations with industry-leading BCMA developers to evaluate nirogacestat in combinations across modalities. SpringWorks has also formed research collaborations with Fred Hutchinson Cancer Research Center and Dana-Farber Cancer Institute to further characterize the ability of nirogacestat to modulate BCMA and potentiate BCMA-directed therapies using a variety of preclinical multiple myeloma models.
Nirogacestat has received Orphan Drug designation from the U.S. Food and Drug Administration (FDA) for the treatment of desmoid tumors and from the European Commission for the treatment of soft tissue sarcoma. The FDA also granted Fast Track and Breakthrough Therapy designations for the treatment of adult patients with progressive, unresectable, recurrent or refractory desmoid tumors or deep fibromatosis.
About SpringWorks Therapeutics
SpringWorks is a clinical-stage biopharmaceutical company applying a precision medicine approach to acquiring, developing and commercializing life-changing medicines for patients with severe rare diseases and cancer. SpringWorks has a differentiated targeted oncology pipeline spanning solid tumors and hematological cancers, including two late-stage clinical trials in rare tumor types as well as several programs addressing highly prevalent, genetically defined cancers. SpringWorks’ strategic approach and operational excellence in clinical development have enabled it to rapidly advance its two lead product candidates into late-stage clinical trials while simultaneously entering into multiple shared-value partnerships with innovators in industry and academia to unlock the full potential for its portfolio and create more solutions for patients with cancer. For more information, visit www.springworkstx.com and follow @SpringWorksTx on Twitter and LinkedIn.
SpringWorks wins FDA priority review for lead candidate
Feb. 27, 2023 7:33 AM ET
SpringWorks Therapeutics, Inc. (SWTX)
By: Dulan Lokuwithana, SA News Editor
- Clinical-stage biotech SpringWorks Therapeutics (NASDAQ:SWTX) announced Monday that the FDA accepted its New Drug Application (NDA) for lead candidate nirogacestat for priority review as a treatment for adults with soft tissue carcinoma desmoid tumors.
- https://seekingalpha.com/news/3941055-swtx-stock-watch-fda-grants-priority-review-lead-asset
- SpringWorks Therapeutics, Inc. (SWTX)
- https://springworkstx.com/pipeline/nirogacestat/
- https://clinicaltrials.gov/ct2/show/NCT03785964?term=nirogacestat&cond=desmoid+tumor&draw=2&rank=1
- https://springworkstx.com/
Nubeqa® (darolutamide)
Nirogacestat (Gamma Secretase Inhibitor)
Nirogacestat (Gamma Secretase Inhibitor)
2/27/2023
Darolutamide receives approval for additional prostate cancer indication in Japan
Darolutamide receives approval for additional prostate cancer indication in Japan
ORION CORPORATION
PRESS RELEASE
27 February 2023 at 9:00 EET
Darolutamide receives approval for additional prostate cancer indication in Japan
- Darolutamide approved for metastatic prostate cancer as well as non-metastatic castration-resistant prostate cancer
- New approval is based on data from the pivotal Phase III ARASENS trial
The Ministry of Health, Labor and Welfare (MHLW) in Japan has approved the oral androgen receptor inhibitor (ARi) darolutamide plus ADT in combination with docetaxel in the indication of metastatic prostate cancer. The MHLW approval is based on the positive results from the Phase III ARASENS trial, which demonstrated that darolutamide plus androgen deprivation therapy (ADT) in combination with docetaxel significantly reduced the risk of death by 32.5% compared to ADT with docetaxel, in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Additionally, the darolutamide combination showed consistent benefits across clinically relevant secondary endpoints, with the overall incidence of treatment-emergent adverse events being similar between treatment arms. These results were published in The New England Journal of Medicine.1
Darolutamide is already approved in Japan for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC) under the brand name Nubeqa®.
Darolutamide plus ADT in combination with docetaxel was recently recommended for EU marketing authorisation for the treatment of mHSPC by the European Medicine Agency’s Committee for Medicinal Products for Human Use (CHMP), with a final decision expected in the coming months. The compound is already approved in its second indication, mHSPC, in a number of markets including the U.S. Filings in other regions are underway or planned by Orion’s collaboration partner Bayer.
Darolutamide is being investigated in a broad development program with three additional ongoing or planned large clinical studies, to evauate its potential across prostate cancer patients from the early- to the late-stage of this disease. This includes the ARANOTE Phase III trial evaluating darolutamide plus androgen deprivation therapy (ADT) versus ADT alone for mHSPC.
Darolutamide is developed jointly by Orion and Bayer.
About the ARASENS Trial
The ARASENS trial is a randomized, Phase III, multi-center, double-blind, placebo-controlled trial which was prospectively designed to investigate the efficacy and safety of oral darolutamide, an androgen receptor inhibitor (ARi), plus androgen deprivation therapy (ADT) and the chemotherapy docetaxel in patients with metastatic hormone-sensitive prostate cancer (mHSPC). A total of 1,306 newly diagnosed patients were randomized in a 1:1 ratio to receive 600 mg of darolutamide twice a day or matching placebo, plus ADT and docetaxel.
The primary endpoint of this trial was overall survival (OS). Secondary endpoints included time to castration-resistant prostate cancer (CRPC), time to pain progression, time to first symptomatic skeletal event (SSE), time to initiation of subsequent anticancer therapy, all measured at 12‐week intervals, as well as adverse events (AEs) as a measure of safety and tolerability. Results from this trial were published in the New England Journal of Medicine.1 A plain language summary publication of these data was published in Future Oncology.2 The ARASENS trial demonstrated that darolutamide plus androgen deprivation therapy (ADT) and docetaxel significantly reduced the risk of death by 32.5% compared to ADT plus docetaxel.1 Improvements in the secondary endpoints supported the benefit observed in the primary endpoint, overall survival.1
About Metastatic Hormone-Sensitive Prostate Cancer
Prostate cancer is the second most commonly diagnosed malignancy in men worldwide. In 2020, an estimated 1.4 million men were diagnosed with prostate cancer, and about 375,000 died from the disease worldwide.3
At the time of diagnosis, most men have localized prostate cancer, meaning their cancer is confined to the prostate gland and can be treated with curative surgery or radiotherapy. Upon relapse, when the disease will metastasise or spread, or if the disease is newly diagnosed, but has already spread, the disease is hormone-sensitive and androgen deprivation therapy (ADT) is the cornerstone of treatment for this hormone-sensitive disease. Current treatment options for men with metastatic hormone-sensitive prostate cancer (mHSPC) include hormone therapy, such as ADT, androgen receptor pathway inhibitors plus ADT or a combination of docetaxel chemotherapy and ADT. Despite these treatments, a large proportion of men with mHSPC will eventually experience progression to metastatic castration-resistant prostate cancer (mCRPC), a condition with limited survival.
About darolutamide
Darolutamide is an oral androgen receptor inhibitor (ARi) with a distinct chemical structure that binds to the receptor with high affinity and exhibits strong antagonistic activity, thereby inhibiting the receptor function and the growth of prostate cancer cells. The low potential for blood-brain barrier penetration for darolutamide is supported by preclinical models and neuroimaging data in healthy humans. This is supported by the overall low incidence of central nervous system (CNS)-related adverse events (AEs) compared to placebo as seen in the ARAMIS Phase III trial4 and the maintained verbal learning and memory observed in the darolutamide arm of the Phase II ODENZA trial.5
The product is approved under the brand name Nubeqa® in more than 80 countries around the world, including the U.S., EU, Japan and China, for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC), who are at high risk of developing metastatic disease. It is also approved for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC) in a number of markets including the U.S. Filings in other regions are underway or planned by Bayer. The compound is also being investigated in further studies across various stages of prostate cancer, including in the ARANOTE Phase III trial evaluating darolutamide plus androgen deprivation therapy (ADT) versus ADT alone for metastatic hormone-sensitive prostate cancer (mHSPC), as well as the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) led international Phase III co-operative group DASL-HiCaP (ANZUP1801) trial evaluating darolutamide as an adjuvant treatment for localised prostate cancer with very high risk of recurrence. Information about these trials can be found at www.clinicaltrials.gov. In addition, a study to explore the potential of darolutamide in the early setting for patients who have experienced a rise in their prostate specific antigen (PSA) levels following surgery or radiation, is also planned.
Orion wins approval for darolutamide in Japan for metastatic prostate cancer
Feb. 27, 2023 6:12 AM ET
Orion Oyj (ORINY), BAYZF, BAYRY
By: Dulan Lokuwithana, SA News Editor
- Finnish pharmaceutical company Orion (OTCPK:ORINY) announced Monday that the government of Japan approved its oral androgen receptor inhibitor darolutamide for metastatic prostate cancer in combination with androgen deprivation therapy (ADT) and docetaxel.
- Darolutamide, which is developed by Orion (OTCPK:ORINY) in partnership with Bayer (OTCPK:BAYZF) (OTCPK:BAYRY), is already approved in Japan as Nubeqa for non-metastatic castration-resistant prostate cancer (nmCRPC).
- Orion Oyj (ORINY), BAYZF, BAYRY
- https://seekingalpha.com/news/3941019-orion-wins-japanese-nod-darolutamide-metastatic-prostate-cancer
- https://www.nubeqa-us.com/
- https://www.orion.fi/en/
biotecHOPE™ 2023
AKEEGA® (Niraparib and Abiraterone Acetate Dual Action Tablet) Plus Prednisone or Prednisolone
AKEEGA® (Niraparib and Abiraterone Acetate Dual Action Tablet) Plus Prednisone or Prednisolone
AKEEGA® (Niraparib and Abiraterone Acetate Dual Action Tablet) Plus Prednisone or Prednisolone
Janssen Receives Positive CHMP Opinion for AKEEGA® (Niraparib and Abiraterone Acetate Dual Action Tablet) Plus Prednisone or Prednisolone for the Treatment of Adult Patients with BRCA1/2 Gene-Mutated Metastatic Castration Resistant Prostate Cancer
Feb 24, 2023Belgium
If approved, niraparib in combination with abiraterone acetate (AA), will be the first dual action tablet (DAT) available in the European Union for first-line treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) with BRCA1/2 mutations, when given with prednisone (P) or prednisolone.[1]
The positive CHMP opinion is based on results from the Phase 3 MAGNITUDE study where the addition of niraparib to AA plus P significantly improved radiographic progression-free survival (rPFS) compared to standard of care in untreated mCRPC patients with BRCA1/2 mutations.[2]
BEERSE, Belgium, 24 February 2023 – The Janssen Pharmaceutical Companies of Johnson & Johnson announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended marketing authorisation for AKEEGA® (niraparib and AA), in the form of a DAT, given with P or prednisolone, for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) and BRCA1/2 mutations (germline and/or somatic) in whom chemotherapy is not clinically indicated.1
Niraparib is a highly selective poly adenosine diphosphate-ribose polymerase (PARP) inhibitor.2 Together with AA, a cytochrome P450 17α-hydroxylase (CYP17) inhibitor,[3] the combination DAT regimen targets two oncogenic drivers (mutations responsible for both the development and maintenance of prostate cancer) in patients with mCRPC, namely androgen receptor axis (AR-axis) and BRCA1/2 gene mutations.[4],[5]
Prostate cancer is the most common cancer in men in Europe.[6] Despite treatment advances, for those whose cancer has progressed to mCRPC, the impact can be devastating with an average overall survival ranging from 13-36 months.[7],[8],[9] Patients with mCRPC and BRCA gene mutations are more likely to have aggressive disease, poor outcomes and a shorter survival time.[10],[11],[12],[13] BRCA1/2 gene mutations have been identified in approximately 10-15 percent of patients with mCRPC.[14],[15]
“Metastatic castration-resistant prostate cancer remains a lethal disease, with high unmet needs in terms of treatment options, particularly for patients with BRCA1/2 gene mutations,” said Elena Castro*, Consultant Oncologist, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre, Madrid, Spain. “We’ve seen that in these patients, niraparib combined with abiraterone acetate and prednisone significantly reduces the risk of disease progression or death compared to AAP. This niraparib-based regimen is a welcomed targeted treatment option and, if approved, has the potential to impact the standard of care for men with mCRPC BRCA who are treated with first-line therapy.”
“In recent years, we’ve focused on precision medicine in prostate cancer because we know patients with gene mutations, such as BRCA1/2, face a worse prognosis than those without,” said Martin Vogel, EMEA Therapeutic Area Lead Oncology, Janssen-Cilag GmbH. “The positive CHMP opinion reinforces the benefit of this niraparib combination and marks an important milestone in addressing BRCA1/2 mutations as we continue to drive progress towards changing the outlook for patients with mCRPC.”
The positive CHMP opinion is based on results of the randomised, double-blind, placebo controlled, Phase 3 MAGNITUDE study (NCT03748641) which assessed whether the addition of niraparib to AAP improved outcomes in those with first-line mCRPC, with or without alterations in homologous recombination repair (HRR) associated genes.1,16 Patients with HRR gene alterations were randomised to receive niraparib 200 mg once daily plus AAP [n=212], or placebo and AAP [n=211]. In MAGNITUDE, a total of 423 patients with HRR gene alterations were enrolled, 225 (53.2 percent) of whom had BRCA mutations.14 This is the largest cohort of BRCA1/2-positive patients with mCRPC.16 First results, presented at the American Society of Clinical Oncology – Genitourinary Cancers Symposium (ASCO GU) 2022 Annual Meeting,2 showed niraparib plus AAP significantly improved rPFS (as analysed by blinded independent central review) in all HRR-positive patients. This improvement was most pronounced in patients with BRCA1/2 gene mutations, where a statistically significant 47 percent risk reduction was observed for rPFS (HR 0.53; p=0.001).2 Updated results from the second interim analysis (IA2) of MAGNITUDE were presented at the recent ASCO GU 2023 Annual Meeting.[16] In the IA2, at 24.8 months of median follow-up in the BRCA subgroup, rPFS by central review demonstrated a consistent and clinically meaningful treatment effect favouring niraparib plus AAP, with a median rPFS of 19.5 months compared with 10.9 months for placebo plus AAP. Additionally, in the BRCA subgroup, there was a trend towards improved overall survival (OS) with niraparib plus AAP, strong improvement in time to symptomatic progression (TSP) and continued consistent improvement of time-to-initiation of cytotoxic chemotherapy (TCC).16
The observed safety profile of the combination of niraparib and AAP was consistent with the known safety profile of each agent.2 Of the patients with HRR gene alterations, 67 percent experienced Grade 3/4 adverse events (AEs) in the combination arm versus 46.4 percent in the control arm. Discontinuation rates due to AEs for the combination arm and control arm were 10.8 percent and 4.7 percent, respectively. The combination of niraparib and AAP also maintained overall quality of life in comparison with placebo and AAP as measured on the Functional Assessment of Cancer Therapy–Prostate (FACT-P) scale.2
“Prostate cancer is a heterogeneous disease made up of many biologically distinct subpopulations. The data from MAGNITUDE supports the significant value of biomarker testing to identify the subgroup of patients most likely to derive a clinical benefit from a targeted treatment, and overcome the poor prognosis of mCRPC with BRCA mutations,” said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumors, Janssen Research & Development, LLC. “At Janssen, we are dedicated to continued innovation in prostate cancer and now look forward to working with health authorities to bring this niraparib-based treatment option to patients as soon as possible.”
#ENDS#
About Niraparib
Niraparib is an orally administered, highly selective poly (ADP ribose) polymerase (PARP) inhibitor, that is currently being studied by Janssen for the treatment of patients with prostate cancer.4 Additional ongoing studies include the Phase 3 AMPLITUDE study (NCT04497844) evaluating the combination of niraparib and AAP in a HRR biomarker-selected patient population with metastatic hormone-sensitive prostate cancer (mHSPC).[17]
In April 2016, Janssen Biotech, Inc. entered into a worldwide (except Japan) collaboration and license agreement with TESARO, Inc. (acquired by GSK in 2019), for exclusive rights to niraparib in prostate cancer.[18]
In the EU, niraparib is indicated as monotherapy for the maintenance treatment of adult patients with advanced epithelial high-grade ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response following completion of first-line platinum-based chemotherapy; and as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed high grade serious epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy.5 Niraparib is currently marketed by GSK as ZEJULA®.5
About abiraterone acetate
Abiraterone acetate is an orally administered androgen biosynthesis inhibitor. In the European Union, abiraterone acetate is indicated with prednisone or prednisolone for the treatment of newly diagnosed high risk mHSPC in adult men in combination with androgen deprivation therapy (ADT); the treatment of mCRPC in adult men who are asymptomatic or mildly symptomatic after failure of ADT in whom chemotherapy is not yet clinically indicated; and the treatment of mCRPC in adult men whose disease has progressed on or after a docetaxel-based chemotherapy regimen.3
Abiraterone acetate is currently marketed by Janssen-Cilag International NV as ZYTIGA®.3
About Metastatic Castration-Resistant Prostate Cancer
Metastatic castration-resistant prostate cancer (mCRPC) characterises cancer that no longer responds to ADT and has spread to other parts of the body.[19] The most common metastatic sites are bones, followed by the lymph nodes, liver and lungs.[20] Prostate cancer is the most common cancer in men in Europe.6 In 2020, more than one million men around the world were diagnosed with prostate cancer.[21] Patients with mCRPC and HRR gene alterations, of which BRCA mutations are the most common, are more likely to have aggressive disease, poor outcomes and a shorter survival time.10,11,12,13
About MAGNITUDE
MAGNITUDE (NCT03748641) is a Phase 3 randomised, double-blind, placebo-controlled, multicentre clinical study evaluating the safety and efficacy of the combination of niraparib and AAP for patients with mCRPC, with or without certain HRR gene alterations and who have not received prior therapy for mCRPC except for standard of care, next-generation androgen receptor inhibitors and up to 4 months of AAP.4 The study includes patients with (HRR biomarker [BM] positive; ATM, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, HDAC2, PALB2) and without specified gene alterations (HRR BM negative), who were randomised 1:1 to receive niraparib 200 mg once daily plus AAP or placebo plus AAP.4 Additionally in an open-label cohort of HRR-positive patients, all patients received the DAT formulation of niraparib and abiraterone acetate plus prednisone. The primary endpoint of the MAGNITUDE trial is rPFS assessed by blinded independent central review. Secondary endpoints include time-to-initiation of cytotoxic chemotherapy, time to symptomatic progression and overall survival.4
About the Janssen Pharmaceutical Companies of Johnson & Johnson
At Janssen, we're creating a future where disease is a thing of the past. We're the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular, Metabolism & Retina; Immunology; Infectious Diseases & Vaccines; Neuroscience; Oncology; and Pulmonary Hypertension.
Learn more at www.janssen.com/emea/. Follow us at www.twitter.com/JanssenEMEA for our latest news. Janssen Pharmaceutica NV, Janssen-Cilag GmBH and Janssen Research & Development, LLC are part of the Janssen Pharmaceutical Companies of Johnson & Johnson.
*Dr. Castro has served as a consultant to Janssen; she has not been paid for any media work.
Johnson & Johnson wins EU nod for prostate cancer therapy
Feb. 24, 2023 2:12 PM ET
By: Dulan Lokuwithana, SA News Editor2 Comments
Johnson & Johnson's (NYSE:JNJ) Janssen unit announced Friday that a group of experts from the European Medicines Agency (EMA) recommended marketing authorization for its oral PARP inhibitor niraparib as a combination regimen for certain adults with prostate cancer.
With its latest decision, EMA's Committee for Medicinal Products for Human Use (CHMP) recommends niraparib with abiraterone acetate as Akeega for adults with metastatic castration-resistant prostate cancer (mCRPC) and BRCA1/2 mutations.
https://seekingalpha.com/news/3940807-johnson-johnson-wins-eu-nod-for-prostate-cancer-therapy
ALTUVIIIO™ (Efanesoctocog alfa (formerly BIVV001))
AKEEGA® (Niraparib and Abiraterone Acetate Dual Action Tablet) Plus Prednisone or Prednisolone
AKEEGA® (Niraparib and Abiraterone Acetate Dual Action Tablet) Plus Prednisone or Prednisolone
PRESS RELEASES •
February 23, 2023
Press Release: FDA approves once-weekly ALTUVIIIO™, a new class of factor VIII therapy for hemophilia A that offers significant bleed protection
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- Press Release: FDA approves once-weekly ALTUVIIIO™, a new class of factor VIII therapy for hemophilia A that offers significant bleed protection
FDA approves once-weekly ALTUVIIIO™, a new class of factor VIII therapy for hemophilia A that offers significant bleed protection
Paris and Stockholm – February 23, 2023 – The U.S. Food and Drug Administration (FDA) has approved ALTUVIIIO™ [Antihemophilic Factor (Recombinant), Fc-VWF-XTEN Fusion Protein-ehtl], previously referred to as efanesoctocog alfa, a first-in-class, high-sustained factor VIII replacement therapy. ALTUVIIIO is indicated for routine prophylaxis and on-demand treatment to control bleeding episodes, as well as perioperative management (surgery) for adults and children with hemophilia A. ALTUVIIIO is the first and only hemophilia A treatment that delivers normal to near-normal factor activity levels (over 40%) for most of the week with once-weekly dosing, and significantly reduces bleeds compared to prior factor VIII prophylaxis.
Paul Hudson
CEO, Sanofi
"Today’s approval of ALTUVIIIO allows patients and physicians to reimagine living with hemophilia. The high sustained factor activity levels that can be achieved with ALTUVIIIO have the potential to change the hemophilia landscape. For the first time, with a once-weekly dose, powerful bleed protection is a reality for patients. Significant shifts in treatment paradigms that improve people’s lives, like ALTUVIIIO, are what we have committed to delivering at Sanofi.”
Hemophilia A is a rare, lifelong condition in which the ability of a person’s blood to clot properly is impaired, leading to excessive bleeds and spontaneous bleeds into joints that can result in joint damage and chronic pain, and potentially impact quality of life. The severity of hemophilia is determined by the level of clotting factor activity in a person’s blood, and there is a negative correlation between risk of bleeding and factor activity levels.
Lynn Malec, MD
Medical Director of Comprehensive Center for Bleeding Disorders and Associate Investigator at The Versiti Blood Research Institute, and Associate Professor of Medicine and Pediatrics at The Medical College of Wisconsin
“This approval marks an important clinical advancement for the hemophilia community because we have an option that can achieve higher levels of factor activity with a single simplified weekly dose. By maintaining high levels of factor activity throughout the week, patients can be confident in the bleed protection ALTUVIIIO offers.”
This is the first approval of ALTUVIIIO. The FDA evaluated the application under Priority Review, which is granted to therapies that have the potential to provide significant improvements in the treatment, diagnosis, or prevention of serious conditions. The FDA previously granted ALTUVIIIO Breakthrough Therapy designation in May 2022 – the first factor VIII therapy to receive this recognition – Fast Track designation in February 2021, and Orphan Drug designation in August 2017.
Regulatory submission in the EU is anticipated in the second half of 2023. The European Commission granted Orphan Drug designation in June 2019.
ALTUVIIIO helps elevate expectations for hemophilia A by providing protection for longer
The FDA approval is based on data from the pivotal XTEND-1 Phase 3 study recently published in The New England Journal of Medicine. Once-weekly ALTUVIIIO prophylaxis met the primary endpoint, providing significant bleed protection for people with severe hemophilia A with a mean annualized bleeding rate (ABR) of 0.70 (95% CI: 0.5-1.0) and a median ABR of 0.0 (Q1, Q3: 0.0, 1.0). ALTUVIIIO met the key secondary endpoint with a significant reduction of 77% in ABR versus prior factor prophylaxis based on an intra-patient comparison (95% CI:58%-87%).
Additional data showed prevention of joint bleeds with a median annualized joint bleeding rate of 0 (Q1, Q3: 0.0, 1.0). Treatment with ALTUVIIIO provided 100% resolution of target joints, which are joints that have recurrent bleeds (e.g., knee, ankle, or elbow). ALTUVIIIO provided mean factor VIII activity greater than 40% for most of the week and greater than 10% at Day 7; these levels were associated with a low bleed risk. In the study, ALTUVIIIO was well-tolerated and inhibitor development to factor VIII was not detected, although is possible following administration of ALTUVIIIO.
Additionally, interim data from XTEND-Kids showed that children younger than 12 years of age receiving once-weekly ALTUVIIIO for 26 weeks (n=23) experienced a mean ABR of 0.5 (95% CI: 0.2-1.3) and a median ABR of 0 (Q1, Q3: 0.0, 1.3). Safety results were consistent with data from the XTEND-1 trial. The full results from XTEND-Kids will be presented at a future medical meeting.
Across the studies, ALTUVIIIO has an established safety profile and there were no reports of factor VIII inhibitor development, although inhibitor formation is possible following administration of ALTUVIIIO. The most common side effects (>10%) of ALTUVIIIO are headache and arthralgia.
ALTUVIIIO is indicated for routine prophylaxis, on-demand treatment and control of bleeding episodes, and perioperative management of bleeding. The simple recommended dose of 50 IU/kg is intended for all patients and for different clinical scenarios.
To ensure that patients have access to the improved bleed protection provided by ALTUVIIIO, Sanofi will price ALTUVIIIO at parity to the annual cost of treating a prophylaxis patient on Eloctate®[Antihemophilic Factor (Recombinant), Fc Fusion Protein]. Sanofi will also provide comprehensive patient support services and resources online and at 1.855.MyALTUVIIIO (855.692.5888). In the U.S., ALTUVIIIO is expected to be commercially available in April.
About ALTUVIIIO™
ALTUVIIIO [Antihemophilic Factor (Recombinant), Fc-VWF-XTEN Fusion Protein-ehtl] is a novel von Willebrand Factor (VWF) independent recombinant factor VIII therapy that is designed to extend protection from bleeds with once-weekly prophylactic dosing for adults and children with hemophilia A. ALTUVIIIO has a 3 to 4 fold longer half-life relative to standard and extended half-life factor VIII products. It is the first factor VIII therapy that has been shown to break through the von Willebrand factor ceiling, which imposes a half-life limitation on earlier generation factor VIII therapies. ALTUVIIIO builds on the innovative Fc fusion technology by adding a region of von Willebrand factor and XTEN® polypeptides to extend its time in circulation.
About the XTEND Clinical Programs
The XTEND clinical program is comprised of two Phase 3 trials in hemophilia A: XTEND-1 in people 12 years or older and XTEND-Kids in children younger than 12 years old. There is also an ongoing extension study (XTEND-ed).
The Phase 3 XTEND-1 study (NCT04161495) was an open-label, non-randomized interventional study assessing the safety, efficacy, and pharmacokinetics of once-weekly ALTUVIIIO in people 12 years of age or older (n=159) with severe hemophilia A who were previously treated with factor VIII replacement therapy. The study consisted of two parallel treatment arms — the prophylaxis Arm A (n=133), in which patients who had received prior factor VIII prophylaxis were treated with once-weekly intravenous ALTUVIIIO prophylaxis (50 IU/kg) for 52 weeks, and the on-demand Arm B (n=26), in which patients who had received prior on-demand factor VIII therapy began with 26 weeks of on-demand ALTUVIIIO (50 IU/kg), then switched to once-weekly prophylaxis with ALTUVIIIO (50 IU/kg) for an additional 26 weeks.
The primary efficacy endpoint was the mean annualized bleeding rate (ABR) in Arm A, and the key secondary endpoint was an intra-patient comparison of ABR during the ALTUVIIIO weekly prophylaxis treatment period versus the prior factor VIII prophylaxis ABR for a subset of participants in Arm A who had participated in a previous observational study (Study 242HA201/OBS16221).
The XTEND-Kids study (NCT04759131) was an open-label, non-randomized interventional study of the safety, efficacy, and pharmacokinetics of once-weekly ALTUVIIIO in previously treated patients younger than 12 years of age (n=67) with severe hemophilia A. Patients received once-weekly ALTUVIIIO prophylaxis (50 IU/kg) for 52 weeks.
About the Sanofi and Sobi collaboration
Sobi and Sanofi collaborate on the development and commercialization of Alprolix® and Elocta®/Eloctate®. The companies also collaborate on the development and commercialization of efanesoctocog alfa or ALTUVIIIO™ in the US. Sobi has final development and commercialization rights in the Sobi territory (essentially Europe, North Africa, Russia and most Middle Eastern markets). Sanofi has final development and commercialization rights in North America and all other regions in the world excluding the Sobi territory.
About Sobi®
Sobi is a specialized international biopharmaceutical company transforming the lives of people with rare diseases. Providing sustainable access to innovative medicines in the areas of haematology, immunology and specialty care, Sobi has approximately 1,600 employees across Europe, North America, the Middle East and Asia. In 2022, revenue amounted to SEK 18.8 billion. Sobi’s share (STO:SOBI) is listed on Nasdaq Stockholm. More about Sobi at sobi.com, LinkedIn and YouTube.
About Sanofi
We are an innovative global healthcare company, driven by one purpose: we chase the miracles of science to improve people’s lives. Our team, across some 100 countries, is dedicated to transforming the practice of medicine by working to turn the impossible into the possible. We provide potentially life-changing treatment options and life-saving vaccine protection to millions of people globally, while putting sustainability and social responsibility at the center of our ambitions.
Sanofi is listed on EURONEXT: SAN and NASDAQ: SNY
Sanofi wins FDA nod for once-weekly bleeding disorder therapy
Feb. 24, 2023 5:46 AM ET
Sanofi (SNY), SNYNF, BIOVFRHHBY, NVO, BAYRY, BAYZF, NONOF, RHHBF, TAK
By: Dulan Lokuwithana, SA News Editor
- The FDA has greenlighted factor replacement therapy Altuviiio from Sanofi (NASDAQ:SNY) (OTCPK:SNYNF) as a once-weekly treatment for adults and children with an inherited bleeding disorder called hemophilia A, the French drugmaker announced.
- Specifically, the agency has approved Altuviiio for routine prophylaxis and on-demand treatment to control bleeding episodes and for the surgical management of hemophilia A patients.
- With the approval, Sanofi (SNY) and Swedish drug maker Sobi (OTCPK:BIOVF), its partner for U.S. commercialization of Altuviiio, will compete against Roche (OTCQX:RHHBY) (OTCQX:RHHBF), which markets its blockbuster hemophilia A therapy Hemlibra.
- https://seekingalpha.com/news/3940532-sanofi-wins-fda-nod-once-weekly-bleeding-disorder-therapy
- Sanofi (SNY), SNYNF, BIOVF
- https://www.sanofi.com/en/
- https://www.sobi.com/en
MRNA-4157/V940 -MRNA CANCER VACCINE, IN COMBINATION WITH KEYTRUDA(R) (PEMBROLIZUMAB)
AKEEGA® (Niraparib and Abiraterone Acetate Dual Action Tablet) Plus Prednisone or Prednisolone
MRNA-4157/V940 -MRNA CANCER VACCINE, IN COMBINATION WITH KEYTRUDA(R) (PEMBROLIZUMAB)
MODERNA AND MERCK ANNOUNCE MRNA-4157/V940, AN INVESTIGATIONAL PERSONALIZED MRNA CANCER VACCINE, IN COMBINATION WITH KEYTRUDA(R) (PEMBROLIZUMAB), WAS GRANTED BREAKTHROUGH THERAPY DESIGNATION BY THE FDA FOR ADJUVANT TREATMENT OF PATIENTS WITH HIGH-RISK MELANOMA FOLLOWING COMPLETE RESECTION
FEBRUARY, 22, 2023 DOWNLOAD(OPENS IN NEW WINDOW)
Designation based on positive data from Phase 2b KEYNOTE-942/mRNA-4157-P201 trial
CAMBRIDGE, MA and RAHWAY, NJ / ACCESSWIRE / February 22, 2023 / Moderna, Inc. (NASDAQ:MRNA), a biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines, and Merck (NYSE:MRK), known as MSD outside of the United States and Canada, today announced that mRNA-4157/V940, an investigational personalized mRNA cancer vaccine, in combination with KEYTRUDA, Merck's anti-PD-1 therapy, has been granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA) for the adjuvant treatment of patients with high-risk melanoma following complete resection. The FDA granted Breakthrough Therapy Designation based on positive data from the Phase 2b KEYNOTE-942/mRNA-4157-P201 trial.
"The FDA's Breakthrough Designation for mRNA-4157/V940 in combination with KEYTRUDA reflects the excitement that we have for the potential promise of individualized cancer treatments," said Stephen Hoge, M.D., Moderna's President. "mRNA-4157/V940 in combination with KEYTRUDA provided the first demonstration of efficacy for an investigational mRNA cancer treatment in a randomized clinical trial and potentially represents a new frontier in treating melanoma and other cancers. We look forward to publishing the full data set and sharing the results at an upcoming oncology medical conference, as well as continuing discussions with health authorities. We are grateful to the FDA for this designation."
"This is an important milestone in the development of mRNA-4157/V940 in combination with KEYTRUDA," said Dr. Eric H. Rubin, senior vice president, global clinical development, Merck Research Laboratories. "We look forward to working with the FDA, in collaboration with Moderna, to conduct a rigorous and rapid clinical development program with a focus on addressing the needs of this important patient population."
The FDA's Breakthrough Therapy Designation is granted to expedite the development and review of drugs that are intended to treat a serious condition, and when preliminary clinical evidence indicates that the product may demonstrate substantial improvement over available therapies on at least one clinically significant endpoint.[i]
The companies will continue to discuss the results with regulatory authorities, initiate a Phase 3 study in adjuvant melanoma in 2023, and rapidly expand to additional tumor types, including non-small cell lung cancer.
About mRNA-4157/V940
mRNA-4157/V940 is a novel investigational messenger ribonucleic acid (mRNA)-based personalized cancer vaccine consisting of a single synthetic mRNA coding for up to 34 neoantigens that is designed and produced based on the unique mutational signature of the patient's tumor. Upon administration into the body, the algorithmically derived and mRNA-encoded neoantigen sequences are endogenously translated and undergo natural cellular antigen processing and presentation, a key step in adaptive immunity.
Personalized cancer vaccines are designed to prime the immune system so that a patient can generate a tailored antitumor response specific to their tumor mutation signature. mRNA-4157/V940 is designed to stimulate an immune response by generating specific T cell responses based on the unique mutational signature of a patient's tumor. KEYTRUDA is an immunotherapy that works by increasing the ability of the body's immune system to help detect and fight tumor cells. Based on early clinical studies, combining mRNA-4157/V940 with KEYTRUDA may potentially provide an additive benefit and enhance T cell-mediated destruction of tumor cells.
About KEYNOTE-942/mRNA-4157-P201 ( NCT03897881 )
KEYNOTE-942 is an ongoing randomized, open-label Phase 2b trial that enrolled 157 patients with stage III/IV melanoma. Following complete surgical resection, patients were randomized to receive mRNA-4157/V940 (nine total doses of mRNA-4157) and KEYTRUDA (200 mg every three weeks up to 18 cycles [for approximately one year]) versus KEYTRUDA alone for approximately one year until disease recurrence or unacceptable toxicity. The primary endpoint is recurrence-free survival, and secondary endpoints include distant metastasis-free survival and safety.
Key eligibility criteria for the trial included: patients with resectable cutaneous melanoma at high risk of recurrence, patients with complete resection within 13 weeks prior to the first dose of KEYTRUDA, patients were disease free at study entry (after surgery) with no loco-regional relapse or distant metastasis and no clinical evidence of brain metastases.
About Melanoma
Melanoma, the most serious form of skin cancer, is characterized by the uncontrolled growth of pigment-producing cells. The rates of melanoma have been rising over the past few decades, with nearly 325,000 new cases diagnosed worldwide in 2020. In the U.S., skin cancer is one of the most common types of cancer diagnosed, and melanoma accounts for a large majority of skin cancer deaths. Each year, it is estimated there will be nearly 100,000 new cases of melanoma diagnosed and almost 8,000 deaths resulting from the disease in the U.S. The five-year survival rates are estimated to be 60.3% for stage III and 16.2% for stage IV.
About KEYTRUDA® (pembrolizumab) injection, 100 mg
KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body's immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.
Merck has the industry's largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.
Selected KEYTRUDA® (pembrolizumab) Indications in the U.S
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.
KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB, IIC, or III melanoma following complete resection.
Non-Small Cell Lung Cancer
KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.
KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:
- stage III where patients are not candidates for surgical resection or definitive chemoradiation, or
- metastatic.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.
KEYTRUDA, as a single agent, is indicated as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with Stage IB (T2a ≥4 cm), II, or IIIA NSCLC.
Head and Neck Squamous Cell Cancer
KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.
Classical Hodgkin Lymphoma
KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).
KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.
Primary Mediastinal Large B-Cell Lymphoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy.
KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.
Urothelial Carcinoma
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC):
- who are not eligible for any platinum-containing chemotherapy, or
- who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
Non-muscle Invasive Bladder Cancer
KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.
Microsatellite Instability-High or Mismatch Repair Deficient Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.
Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC) as determined by an FDA-approved test.
Gastric Cancer
KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
Esophageal Cancer
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:
- in combination with platinum- and fluoropyrimidine-based chemotherapy, or
- as a single agent after one or more prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
Cervical Cancer
KEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
Hepatocellular Carcinoma
KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
Merkel Cell Carcinoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
Renal Cell Carcinoma
KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).
KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.
Endometrial Carcinoma
KEYTRUDA, as a single agent, is indicated for the treatment of patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
Tumor Mutational Burden-High Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.
Cutaneous Squamous Cell Carcinoma
KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation.
Triple-Negative Breast Cancer
KEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
Pediatric Use
In KEYNOTE-051, 161 pediatric patients (62 pediatric patients aged 6 months to younger than 12 years and 99 pediatric patients aged 12 years to 17 years) were administered KEYTRUDA 2 mg/kg every 3 weeks. The median duration of exposure was 2.1 months (range: 1 day to 24 months).
Adverse reactions that occurred at a ≥10% higher rate in pediatric patients when compared to adults were pyrexia (33%), vomiting (30%), leukopenia (30%), upper respiratory tract infection (29%), neutropenia (26%), headache (25%), and Grade 3 anemia (17%).
Please see Prescribing Information for KEYTRUDA (pembrolizumab) at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf and Medication Guide for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf .
Merck's Focus on Cancer
Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.
About Merck
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world - and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.
About Moderna
In over 10 years since its inception, Moderna has transformed from a research-stage company advancing programs in the field of messenger RNA (mRNA), to an enterprise with a diverse clinical portfolio of vaccines and therapeutics across seven modalities, a broad intellectual property portfolio in areas including mRNA and lipid nanoparticle formulation, and an integrated manufacturing plant that allows for rapid clinical and commercial production at scale. Moderna maintains alliances with a broad range of domestic and overseas government and commercial collaborators, which has allowed for the pursuit of both groundbreaking science and rapid scaling of manufacturing. Most recently, Moderna's capabilities have come together to allow the authorized use and approval of one of the earliest and most effective vaccines against the COVID-19 pandemic.
Moderna's mRNA platform builds on continuous advances in basic and applied mRNA science, delivery technology and manufacturing, and has allowed the development of therapeutics and vaccines for infectious diseases, immuno-oncology, rare diseases, cardiovascular diseases and auto-immune diseases. Moderna has been named a top biopharmaceutical employer by Science for the past eight years. To learn more, visit www.modernatx.com.
[i] U.S. Food and Drug Administration (FDA). Breakthrough Therapy. https://www.fda.gov/forpatients/approvals/fast/ucm405397.htm. Updated January 4, 2018. Accessed January 26, 2023.
SOURCE: Moderna, Inc.
View source version on accesswire.com:
https://www.accesswire.com/740413/Moderna-and-Merck-Announce-mRNA-4157V940-an-Investigational-Personalized-mRNA-Cancer-Vaccine-in-Combination-With-KEYTRUDAR-pembrolizumab-was-Granted-Breakthrough-Therapy-Designation-by-the-FDA-for-Adjuvant-Treatment-of-Patients-With-High-Risk
Moderna, Merck's mRNA cancer vaccine/Keytruda combo gets FDA breakthrough therapy tag
Feb. 23, 2023 5:51 AM ET
By: Ravikash, SA News Editor1 Comment
- The U.S. Food and Drug Administration (FDA) granted breakthrough therapy designation to Moderna (NASDAQ:MRNA) and Merck's (NYSE:MRK) personalized mRNA cancer vaccine mRNA-4157/V940, in combination with Keytruda, for the adjuvant treatment of patients with high-risk melanoma after complete resection.
- https://seekingalpha.com/news/3939727-moderna-mercks-mrna-cancer-vaccinekeytruda-combo-gets-fda-breakthrough-therapy-tag
- Merck & Co., Inc. (MRK), MRNA
RGX-121
Sunlenca® (lenacapavir)
MRNA-4157/V940 -MRNA CANCER VACCINE, IN COMBINATION WITH KEYTRUDA(R) (PEMBROLIZUMAB)
ADDITIONAL POSITIVE INTERIM DATA FROM PHASE I/II/III CAMPSIITE™ TRIAL OF REGENXBIO'S RGX-121 FOR THE TREATMENT OF MPS II (HUNTER SYNDROME) PRESENTED AT 19TH ANNUAL WORLDSYMPOSIUMTM
February 22, 2023 at 3:00 PM EST
- RGX-121, a potential one-time gene therapy for the treatment of MPS II, continues to be well-tolerated with no drug-related SAEs across three dose levels
- Additional data from patients in Cohort 3 using pivotal program dose level continue to demonstrate largest reductions in CSF GAGs, continuing to approach normal levels at 48 weeks
- New, longer-term clinical measures demonstrated continued improvement in neurodevelopmental and daily activity skill acquisition up to three years after RGX-121 administration
- Positive interim data continues to support plan to file Biologics License Application in 2024 using the accelerated approval pathway
ROCKVILLE, Md., Feb. 22, 2023 /PRNewswire/ -- REGENXBIO Inc. (Nasdaq: RGNX) today announced additional positive interim data from the Phase I/II/III CAMPSIITE™ trial of RGX-121 for the treatment of patients up to 5 years old diagnosed with Mucopolysaccharidosis Type II (MPS II), also known as Hunter Syndrome. The results were presented at the 19th Annual WORLDSymposium™.
"These new results demonstrate sustained reductions in CSF GAGs and an encouraging, long-term clinical profile of RGX-121 up to three years," said Steve Pakola, M.D., Chief Medical Officer of REGENXBIO. "GAGs measured in CSF, specifically heparan sulfate, reflect disease manifestations in the CNS and are a direct cause of disease pathophysiology. Our data provide additional evidence to support the finding that meaningful changes in CSF heparan sulfate is an appropriate and reliable surrogate endpoint reasonably likely to predict the clinical benefit of CNS-targeted therapies for MPS II. We are excited to have taken RGX-121 into a pivotal program and plan to file a Biologics License Application in 2024 using the accelerated approval pathway."
"Treatment options to address the neurological manifestations of MPS II remain a significant unmet medical need for patients," said Can Ficicioglu, M.D., Ph.D., Professor of Pediatrics at the Perelman School of Medicine, University of Pennsylvania. "The data presented today are encouraging and continue to show the potential of a one- time gene therapy to provide meaningful, durable clinical benefits to the MPS II community. I look forward to continuing to follow RGX-121 as it progresses through the pivotal program."
RGX-121 is an investigational, one-time gene therapy designed to deliver the gene that encodes the iduronate-2-sulfatase (I2S) enzyme using the AAV9 vector. Data presented were from the Phase I/II portion of the CAMPSIITE trial in which the primary endpoint is to evaluate the safety of RGX-121. Secondary and exploratory endpoints include cerebral spinal fluid (CSF) glycosaminoglycans (GAGs), neurodevelopmental assessments, caregiver reported outcomes and systemic biomarkers. RGX-121 is administered directly to the central nervous system (CNS). As of January 3, 2023, 15 patients had been treated across three dose levels, 1.3x1010 genome copies per gram (GC/g) of brain mass (n=3), 6.5x1010 GC/g of brain mass (n=7), and 2.9x1011 GC/g of brain mass (n=5).
Data Summary and Safety Update
As of January 3, 2023, RGX-121 was reported to be well tolerated across all cohorts with no drug-related serious adverse events (SAEs) in 15 patients dosed. Time of post-administration follow-up ranges from eight weeks to more than three years. Thirteen patients have completed the 48-week immunosuppression regimen per study protocol. Twelve patients were receiving weekly, intravenous enzyme replacement therapy (ERT) at the time of enrollment, per standard of care; five of these patients remain discontinued from ERT at last time point available, per investigator discretion, as allowed in the protocol.
CSF GAGs Data
Biomarker data from patients in all three cohorts indicate encouraging, dose-dependent reductions of CSF GAGs following one-time administration of RGX-121. Heparan sulfate (HS) and D2S6, a component of HS closely correlated with severe MPS II, are GAGs that are key biomarkers of I2S enzyme activity and are being measured in the CSF at baseline and after administration of RGX-121. CSF GAGs have the potential to be considered a surrogate endpoint that is reasonably likely to predict clinical benefit in MPS II disease under the accelerated approval pathway, as buildup of GAGs in the CSF of MPS II patients correlates with clinical manifestations including neurodevelopmental deficits.
The majority of patients in all cohorts demonstrated reductions of CSF HS from baseline at the last time point available with dose-dependent reductions seen at Weeks 8, 24, and 48 post RGX-121 administration. At Week 48, median reduction of CSF HS from baseline was 33.5% in Cohort 1, 48.9% in Cohort 2 and 64.7% in Cohort 3.
Similarly, dose-dependent reductions of CSF HS D2S6 from baseline were observed at last time point available in the majority of patients, with Cohort 3 patients approaching normal levels at 48 weeks. All three cohorts demonstrated a reduction in HS D2S6 with dose-dependent reductions seen at Weeks 8, 24, and 48. Median reductions from baseline of 31.9% in Cohort 1, 71.9% in Cohort 2 and 83.3% in Cohort 3 were seen at Week 48.
In addition, I2S protein concentration in the CSF, which was undetectable in all patients prior to dosing, was measurable in 10 of 11 Cohort 2 and 3 patients after RGX-121 administration.
Neurodevelopmental and Systemic Data
Improvements in neurodevelopmental function and caregiver reported outcomes demonstrated CNS activity on two developmental scales up to three years after RGX-121 administration. As measured by the Bayley Scales of Infant and Toddler Development, 3rd Edition (BSID-III), the majority of participants with baseline function ≥-2 standard deviations (SD) from the normative mean had developmental function that remained within that range on at least two domains. The majority of participants with baseline function below -2SD from the normative mean stabilized or had an increase of ≥ 3 months in age equivalent scores on cognitive, expressive language or fine motor subtests. As measured by the Vineland Adaptive Behavior Scales Second Edition (VABS-II), the majority of participants demonstrated stabilization or ongoing skill acquisition on age-appropriate subtests of communication, daily living and socialization.
Additionally, evidence of systemic enzyme expression and biomarker activity was observed in all cohorts following RGX-121 administration. The majority of patients demonstrated increases in I2S protein concentration levels in plasma following administration of RGX-121. Total urine GAG measures demonstrated evidence of a systemic effect of RGX-121, independent of ERT treatment.
The study findings presented at the 2023 WORLDSymposium will be available under the Presentations & Publications page in the Media section of REGENXBIO's website located at www.regenxbio.com. Dr. Ficicioglu will share this data in a platform presentation at the WORLDSymposium Sunday, February 26, 2023, at 9 a.m. ET.
About the CAMPSIITE™ Trial
CAMPSIITE is a Phase I/II/III multicenter, open-label trial enrolling boys with MPS II, aged four months up to five years of age. As part of a pivotal program expansion, CAMPSIITE is expected to enroll up to 10 MPS II patients to support the BLA filing using the accelerated approval pathway, with the potential to enroll additional patients. These patients will receive a dose of 2.9x1011 GC/g of brain mass of RGX-121, which is the same dose being evaluated in Cohort 3 of the Phase I/II trial. The pivotal program is using commercial-scale cGMP material from REGENXBIO's proprietary, high-yielding suspension-based manufacturing process, named NAVXpress™. In addition to measuring GAGs in the CSF, the trial will continue to collect neurodevelopmental data and caregiver-reported outcomes.
CAMPSIITE is a global trial, which is expected to include sites in the United States, Brazil and Canada. REGENXBIO has begun dosing patients in the pivotal program.
About RGX-121
RGX-121 is designed to use the AAV9 vector to deliver the human iduronate-2-sulfatase gene (IDS) which encodes the iduronate-2-sulfatase (I2S) enzyme to the central nervous system (CNS). Delivery of the IDS gene within cells in the CNS could provide a permanent source of secreted I2S beyond the blood-brain barrier, allowing for long-term cross correction of cells throughout the CNS. RGX-121 has received orphan drug product, rare pediatric disease and Fast Track designations from the U.S. Food and Drug Administration.
About Mucopolysaccharidosis Type II (MPS II)
MPS II, or Hunter Syndrome, is a rare, X-linked recessive disease caused by a deficiency in the lysosomal enzyme iduronate-2-sulfatase (I2S) leading to an accumulation of glycosaminoglycans (GAGs), including heparan sulfate (HS) in tissues which ultimately results in cell, tissue, and organ dysfunction, including in the central nervous system (CNS). MPS II is estimated to occur in 1 in 100,000 to 170,000 births. In severe forms of the disease, early developmental milestones may be met, but developmental delay is readily apparent by 18 to 24 months. Specific treatment to address the neurological manifestations of MPS II remains a significant unmet medical need. Key biomarkers of I2S enzymatic activity in MPS II patients include its substrate heparan sulfate (HS) D2S6, which has been shown to correlate with neurocognitive manifestations of the disorder.
About REGENXBIO Inc.
REGENXBIO is a leading clinical-stage biotechnology company seeking to improve lives through the curative potential of gene therapy. REGENXBIO's NAV Technology Platform, a proprietary adeno-associated virus (AAV) gene delivery platform, consists of exclusive rights to more than 100 novel AAV vectors, including AAV7, AAV8, AAV9 and AAVrh10. REGENXBIO and its third-party NAV Technology Platform Licensees are applying the NAV Technology Platform in the development of a broad pipeline of candidates, including late-stage and commercial programs, in multiple therapeutic areas. REGENXBIO is committed to a "5x'25" strategy to progress five AAV Therapeutics from our internal pipeline and licensed programs into pivotal-stage or commercial products by 2025.
View original content to download multimedia:https://www.prnewswire.com/news-releases/additional-positive-interim-data-from-phase-iiiiii-campsiite-trial-of-regenxbios-rgx-121-for-the-treatment-of-mps-ii-hunter-syndrome-presented-at-19th-annual-worldsymposiumtm-301753564.html
SOURCE REGENXBIO Inc.
Regenxbio touts interim results from trial of pediatric rare disease gene therapy
Feb. 22, 2023 3:35 PM ET
By: Jonathan Block, SA News Editor
- Regenxbio said that interim results of RGX-121, a gene therapy for the rare pediatric inherited condition Mucopolysaccharidosis Type II (MPS II), also known as Hunter Syndrome, were positive.
- https://seekingalpha.com/news/3939376-regenxbio-touts-interim-results-from-trial-of-pediatric-rare-disease-gene-therapy
- REGENXBIO Inc. (RGNX)
- https://regenxbio.com/
- https://regenxbio.com/rgx-121/
Sunlenca® (lenacapavir)
Sunlenca® (lenacapavir)
Sunlenca® (lenacapavir)
February 22, 2023
Gilead Presents Positive Proof-of-Concept Data for Investigational Combination Regimen of Lenacapavir with Broadly Neutralizing Antibodies as a Potential Twice-Yearly Approach for the Treatment of HIV
– Study Demonstrates the Potential of Lenacapavir in Combination with Broadly Neutralizing HIV Antibodies Teropavimab and Zinlirvimab –
– Findings Support Further Evaluation of the Investigational Combination as a Long-Acting HIV Treatment Option in a Phase 2 Study –
FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced data evaluating lenacapavir in combination with broadly neutralizing antibodies (bNAbs) teropavimab and zinlirvimab as a potential long-acting treatment regimen with twice-yearly dosing.Results fromthe Phase 1b clinical trial demonstrated the investigational combination was generally well tolerated with high efficacy in select virologically suppressed participants living with HIV. These data were presented at the 30th Conference on Retroviruses and Opportunistic Infections (CROI).
“Novel long-acting HIV treatment options will drive the next chapter in care and may help meet the therapy needs and preferences of people living with HIV. In this study we found that lenacapavir and bNAbs in a combination approach may have a significant role to play in the future treatment of HIV,” said Dr. Joseph Eron, MD, lead study investigator and the Chief of the Division of Infectious Diseases at the University of North Carolina School of Medicine. “As a clinician who strives to support the people living with the virus under my care, it will be exciting to continue evaluating the combination regimen as a potential twice-yearly long-acting HIV treatment option.”
The study evaluated the safety and efficacy profile of lenacapavir + teropavimab + zinlirvimab in selected adults living with HIV who were virologically suppressed (HIV-1 RNA <50 copies/mL) for ≥2 years while taking antiretroviral therapy (ART). Study participants (n=20) were sensitive to both bNAbs by HIV proviral DNA phenotype and had a CD4 cell count of ≥500 at study entry. The median age was 44 years (14% female, 14% Black, 14% Asian, and 33% Hispanic/Latinx).
Doses of teropavimab and zinlirvimab were weight-based, with participants randomly allocated in a 1:1 ratio into two active treatment groups replacing their baseline ART with lenacapavir (927mg subcutaneous after oral loading) + teropavimab (30mg/kg body weight intravenous) + zinlirvimab (Group 1: 10mg/kg body weight; Group 2: 30mg/kg body weight, both intravenous).
At Week 26, 90% of participants receiving the complete study regimen (n=18/20) maintained virologic suppression (HIV-1 RNA ≤50 copies/mL). At Week 12, one participant withdrew from the study with documented viral suppression (HIV-1 RNA <50 copies/mL). At Week 16, one participant had a confirmed virologic rebound and later resuppressed on baseline oral ART. There were no serious adverse events (AEs), including no grade 4 or 5 AEs, and no AEs that led to study drug discontinuation. Two participants experienced grade 3 AEs with one experiencing injection site cellulitis and the other experiencing injection site erythema.
“We’re excited to share these promising results that reinforce lenacapavir’s potential to be a foundational agent for long-acting combination HIV treatment options, and we are especially pleased to see the potential of the combination of lenacapavir plus bNAbs dosed once every six months,” said Jared Baeten, MD, PhD, Vice President, HIV Clinical Development, Gilead Sciences. “We are committed to exploring novel therapy approaches that may help deliver care for all people living with HIV, with a focus on developing person-centric options that fit into the diverse lives of people living with the virus, as we continue in our pursuit of ending the HIV epidemic for everyone, everywhere.”
The combination of lenacapavir with teropavimab and zinlirvimab will advance to a Phase 2 study (NCT05729568) later this year in virologically suppressed people living with HIV. The study will assess two different dose levels of the bNAbs and assess safety and efficacy of the regimen in participants followed longitudinally for multiple doses of the study regimen. For more information, please visit: https://clinicaltrials.gov/ct2/show/NCT05729568
Lenacapavir is being developed as a foundation for future HIV therapies with the goal of offering both long-acting oral and injectable options with several dosing frequencies, in combination with other antiretroviral agents for treatment or as monotherapy for prevention, that help address individual patient needs and preferences. Lenacapavir is being evaluated as a long-acting option in multiple ongoing and planned early and late-stage clinical studies in Gilead's prevention and treatment research program.
Sunlenca® (lenacapavir), alone or in combination, is not approved by any regulatory authority outside of the United States, United Kingdom, Canada or the European Union for any use.
Please see below for the U.S. Indication and Important Safety Information for Sunlenca.
Teropavimab (GS-5423) and zinlirvimab (GS-2872) are investigational compounds and are not approved by the U.S. Food and Drug Administration or any other regulatory authority for any use. The use of these compounds in combination with lenacapavir are investigational. Their safety and efficacy are unknown.
There is currently no cure for HIV or AIDS.
About Sunlenca
Sunlenca (300 mg tablet and 463.5 mg/1.5 mL injection) [(lenacapavir)] is a first-in-class, long-acting HIV capsid inhibitor approved in the United States, the United Kingdom, Canada and the European Union, for the treatment of HIV infection, in combination with other antiretroviral(s), in people with multi-drug resistant HIV who are heavily treatment-experienced. Sunlenca tablets are approved for oral loading during initiation of Sunlenca treatment, prior to or at the time of the first long-acting lenacapavir injection depending on initiation option. Sunlenca is the only HIV treatment option administered twice-yearly.
The multi-stage mechanism of action of Sunlenca’s active pharmaceutical agent, lenacapavir, is distinguishable from other currently approved classes of antiviral agents. While most antivirals act on just one stage of viral replication, Sunlenca is designed to inhibit HIV at multiple stages of its lifecycle and has no known cross resistance exhibited in vitro to other existing drug classes.
U.S. Indication for Sunlenca
Sunlenca, a human immunodeficiency virus type 1 (HIV-1) capsid inhibitor, in combination with other antiretroviral(s), is indicated for the treatment of HIV-1 infection in heavily treatment-experienced adults with multidrug resistant HIV-1 infection failing their current antiretroviral regimen due to resistance, intolerance, or safety considerations.
About Gilead Sciences
Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases and address unmet needs in virology, oncology and inflammation.
For 35 years, Gilead has been a leading innovator in the field of HIV, driving advances in treatment, prevention and cure research. Gilead researchers have developed 12 HIV medications, including the first single-tablet regimen to treat HIV, the first antiretroviral for pre-exposure prophylaxis (PrEP) to reduce the risk of acquiring HIV infection, and the first long-acting injectable HIV treatment medication administered twice-yearly. Our advances in medical research have helped to transform HIV into a treatable, preventable, chronic condition for millions of people.
Gilead is committed to continued scientific innovation to provide solutions for the evolving needs of people affected by HIV around the world. Through partnerships and collaborations, the company also aims to improve education, expand access and address barriers to care, with the goal of ending the HIV epidemic for everyone, everywhere. Gilead was recognized as the number one philanthropic funder of HIV-related programs in a report released by Funders Concerned About AIDS.
Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California.
U.S. full Prescribing Information for Sunlenca is available at www.gilead.com .
Sunlenca, Gilead and the Gilead logo are registered trademarks of Gilead Sciences, Inc., or its related companies. All other trademarks are the property of their respective owner(s).
For more information about Gilead, please visit the company’s website at www.gilead.com , follow Gilead on Twitter ( @Gilead Sciences ) and LinkedIn , or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
Source: Gilead Sciences, Inc.
Gilead posts Phase 1 data to support twice yearly potential of HIV therapy
Feb. 22, 2023 12:05 PM ET
By: Dulan Lokuwithana, SA News Editor
Gilead Sciences (NASDAQ:GILD) announced Phase 1 data for its HIV antiviral lenacapavir on Wednesday to support its twice-yearly use along with investigational HIV antibodies Teropavimab and Zinlirvimab.
https://seekingalpha.com/news/3939164-gilead-posts-data-support-twice-yearly-potential-hiv-therapy
Elranatamab
Sunlenca® (lenacapavir)
Sunlenca® (lenacapavir)
Pfizer’s Elranatamab Receives FDA and EMA Filing Acceptance
Wednesday, February 22, 2023 - 06:45am
- Submissions based on favorable MagnetisMM-3 trial results in patients with relapsed or refractory multiple myeloma
NEW YORK--(BUSINESS WIRE)-- Pfizer Inc. (NYSE:PFE) announced today that the U.S. Food and Drug Administration (FDA) has granted Priority Review for the company’s Biologics License Application (BLA) for elranatamab, an investigational B-cell maturation antigen (BCMA) CD3-targeted bispecific antibody (BsAb), for the treatment of patients with relapsed or refractory multiple myeloma (RRMM). Priority Review is intended to direct attention and resources from regulatory authorities toward drugs that, if approved, could offer significant improvements over existing options for serious conditions in order to make these drugs available to patients faster. The FDA’s decision on the application is expected in 2023. The European Medicines Agency (EMA) has also accepted elranatamab’s marketing authorization application (MAA). The company is working closely with the EMA to facilitate their review and will provide updates on timing as appropriate.
"Today, multiple myeloma is a fatal hematologic malignancy, with a median survival of just over five years. As an off-the-shelf treatment, BCMA bispecific antibodies are heralding a new treatment paradigm that can greatly impact the lives of people with this disease.” said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology and Rare Disease, Pfizer Global Product Development. “We believe that elranatamab, if approved, has the potential to become the next standard of care for multiple myeloma given its favorable clinical results and convenient subcutaneous route of administration. We look forward to working with the FDA and EMA to bring this new innovative medicine to patients globally.”
Elranatamab is designed to bind to BCMA, which is highly expressed on the surface of multiple myeloma (MM) cells, and CD3 receptors found on the surface of T-cells, bridging them together and activating the T-cells to kill the myeloma cells. The BLA and MAA for elranatamab are primarily based on data from cohort A (BCMA-naïve - n=123) of MagnetisMM-3 (NCT04649359), an ongoing, open-label, multicenter, single-arm, Phase 2 study designed to evaluate the safety and efficacy of elranatamab monotherapy in patients with RRMM. Enrolled patients represent a heavily pretreated population, who previously received at least three classes of therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
With a median follow up of 10.4 months, patients who received elranatamab as their first BCMA-targeted therapy achieved a high objective response rate of 61% (55% had a very good partial response rate or better), with an 84% probability of maintaining the response at nine months. The MagnetisMM-3 results also suggest elranatamab has a manageable safety profile. The two-step-up priming dose regimen (12/32 mg) helped mitigate the rate and severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) among the 119 patients in cohort A who were treated with this priming regimen. All cases of CRS were Grade 1 or 2 and the majority occurred after the first (43% of patients) or second (24% of patients) dose, with only 6% of patients experiencing CRS after dose 3 and fewer than 1% experiencing CRS after dose 4. Observed cases of ICANS (3%) were neither common nor severe (Grade 1/2 only were reported). No fatal neurotoxicity events were observed. These data were presented at the 64th American Society of Hematology Annual Meeting and Exposition in December 2022.
This study is part of the MagnetisMM clinical research program that expands to additional patient populations over time, with ongoing registrational-intent trials that explore elranatamab both as monotherapy and in combination with standard or novel therapies, spanning multiple patient populations, from newly diagnosed MM to RRMM. This includes MagnetisMM-5 (NCT05020236) in the double class exposed setting, MagnetisMM-6 (NCT05623020) in transplant ineligible newly diagnosed patients, and MagnetisMM-7 (NCT05317416) as maintenance treatment in newly diagnosed patients after transplant, all of which are currently enrolling.
In November 2022, Pfizer announced that elranatamab was granted Breakthrough Therapy Designation by the FDA. In addition, elranatamab has been granted Orphan Drug Designation by the FDA and the EMA for the treatment of MM. The FDA and EMA have also granted elranatamab Fast Track Designation and the PRIME scheme, respectively, for the treatment of patients with RRMM. The UK Medicines and Healthcare Products Regulatory Agency (MHRA) has granted elranatamab Innovative Medicine Designation and the Innovation Passport for the treatment of MM. The FDA has accepted elranatamab for Project ORBIS, which is a framework for the concurrent submission and review of oncology products to potentially expedite approvals in certain countries outside of the US; currently 5 countries (Switzerland, Brazil, Canada, Australia, and Singapore) have accepted to participate.
About Elranatamab
Elranatamab is an investigational, off-the-shelf, humanized BCMA CD3-targeted BsAb. BsAbs are a novel form of cancer immunotherapy that bind to and engage two different targets at once. One arm binds directly to specific antigens on cancer cells and the other arm binds to T-cells, bringing both cell types together. The binding affinity of elranatamab for BCMA and CD3 has been engineered to elicit potent T-cell-mediated anti-myeloma activity. Elranatamab is administered subcutaneously, which offers more convenience over intravenous administration.
About MagnetisMM-3
MagnetisMM-3 (NCT04649359) is an ongoing, open-label, multicenter, single-arm, Phase 2 study designed to evaluate the safety and efficacy of elranatamab monotherapy in patients with RRMM. Patients received subcutaneous (SC) elranatamab 76 mg weekly (QW) on a 28-day cycle with a step-up priming dose regimen, wherein 12 mg and 32 mg are administered on Day 1 and Day 4, respectively, during Cycle 1. For patients receiving 6 or more cycles and achieving a partial response or better for at least 2 months, the dosing interval was once every two weeks (Q2W).
About Multiple Myeloma
MM is a blood cancer that affects plasma cells made in the bone marrow. Healthy plasma cells make antibodies that help the body fight infection. There are over 34,000 new cases of MM diagnosed annually in the U.S. and 176,000 globally.1,2 Despite treatment advances, there is currently no cure. The median survival is just over five years, and most patients receive four or more lines of therapy.3
About Pfizer in Hematology
At Pfizer, we have an industry-leading portfolio of 24 approved innovative cancer medicines and biosimilars, including seven therapies to treat hematologic malignancies. We have taken bold new approaches over the past decade to translate scientific research into transformative medicines for people living with blood cancer. For the millions living with blood cancer today and for those diagnosed tomorrow, we work tirelessly to deliver on our mission: Breakthroughs that change patients’ lives.
About Pfizer: Breakthroughs That Change Patients’ Lives
At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world’s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 170 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.Pfizer.com. In addition, to learn more, please visit us on www.Pfizer.com and follow us on Twitter at @Pfizer and @Pfizer News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.
View source version on businesswire.com: https://www.businesswire.com/news/home/20230222005105/en/
Source: Pfizer Inc.
Pfizer's blood cancer drug elranatamab gets review in US, EU
Feb. 22, 2023 7:20 AM ET
By: Ravikash, SA News Editor
- The U.S. Food and Drug Administration (FDA) granted priority review to Pfizer's (NYSE:PFE) application seeking approval of elranatamab to treat patients with relapsed or refractory multiple myeloma (RRMM).
- https://seekingalpha.com/news/3938950-pfizers-blood-cancer-drug-elranatamab-gets-review-in-us-eu
- Pfizer Inc. (PFE)
- https://www.pfizer.com/science/drug-product-pipeline
Taldefgrobep alfa (also known as BHV2000)
(RSV) vaccine candidate PF-06928316 or RSVpreF
(RSV) vaccine candidate PF-06928316 or RSVpreF
FEBRUARY 21, 2023 AT 7:30 AM EST
Biohaven's Taldefgrobep Alfa Receives FDA Fast Track Designation for Spinal Muscular Atrophy
- Taldefgrobep alfa, a myostatin-targeting biologic investigational agent, in Phase 3 development to increase muscle mass for Spinal Muscular Atrophy patients now granted Fast Track in addition to previously receiving Orphan Drug Designation in the US
NEW HAVEN, Conn., Feb. 21, 2023 /PRNewswire/ -- Biohaven Ltd. (NYSE: BHVN; "Biohaven") announced today that it received Fast Track designation from the U.S. Food and Drug Administration (FDA) for taldefgrobep alfa, a novel anti-myostatin adnectin, for the treatment of spinal muscular atrophy (SMA). Fast Track designation enables important new drugs to reach patients earlier by facilitating more frequent communications with the FDA and expeditious review of a drug which treats a serious condition and fills an unmet medical need. Biohaven previously received orphan drug designation from the FDA for taldefgrobep in the treatment of SMA.
SMA is a rare, progressively debilitating motor neuron disease in which development and growth of muscle mass are compromised, resulting in progressive weakness and muscle atrophy, reduced motor function, impaired quality of life and often death. Inhibition of myostatin, a naturally occurring protein that limits skeletal muscle growth, an important process in healthy muscular development, is a potential therapeutic target for SMA.
Taldefgrobep has the potential to be a novel therapy to be used in combination with disease modifying therapies to enhance muscle function by blocking myostatin activity. Taldefgrobep's novelty in a field of myostatin inhibitors is based on its mechanism of action. It binds to myostatin to both lower overall myostatin levels and also function as a receptor antagonist, thereby blocking myostatin signaling in skeletal muscles.
Lindsey Lee Lair, M.D., M.B.A., F.A.A.N, Vice President, Clinical Development, Biohaven commented, "We are very pleased the FDA granted Fast Track designation for taldefgrobep alfa for the treatment of SMA. Children and adults living with SMA experience significant muscle weakness and functional impairments affecting their quality of life daily, and a substantial unmet medical need persists. We are excited about the potential for taldefgrobep alfa to improve the lives of patients and families affected by SMA."
Karen Chen, Ph.D., CEO, SMA Foundation, added, "Fast Track designation from the FDA underscores the high unmet medical need in SMA and supports the need for additional novel combination therapies in children and adults living with this progressive neurologic disease. The SMA Foundation is heavily investing in supporting the development of additional muscle and neuromuscular regenerative medicine therapies that provide functional benefits to patients. We are happy to see the commitment of health authorities to rapidly advance the development of new therapies"
As a leader in innovative trials addressing neurodegenerative diseases, Biohaven is currently enrolling a Phase 3 clinical trial of taldefgrobep in SMA: A Study to Evaluate the Efficacy and Safety of Taldefgrobep Alfa in Participants with Spinal Muscular Atrophy (RESILIENT) (NCT05337553).
About Taldefgrobep alfa
Taldefgrobep alfa (also known as BHV2000) is a modified adnectin designed to specifically bind to myostatin (GDF-8). Taldefgrobep is a fully human anti-myostatin recombinant protein that lowers free myostatin and acts as an Activin 2b receptor antagonist with the myostatin-taldefgrobep complex. Adnectins are an established proprietary protein therapeutic class based on human fibronectin, an extracellular protein that is naturally abundant in human serum.
About Biohaven
Biohaven is a global clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of life-changing therapies for people with debilitating neurological and neuropsychiatric diseases, including rare disorders. The company is advancing a pipeline of therapies for diseases with little or no treatment options, leveraging its proven drug development capabilities and proprietary platforms, including Kv7 ion channel modulation for epilepsy and neuronal hyperexcitability; glutamate modulation for obsessive-compulsive disorder and spinocerebellar ataxia and myostatin inhibition for neuromuscular diseases. Biohaven's portfolio of early- and late-stage product candidates also includes discovery research programs focused on TRPM3 channel activation for neuropathic pain, CD-38 antibody recruiting, bispecific molecules for multiple myeloma, antibody drug conjugates (ADCs), and extracellular target degrader platform technology (MoDE™) with potential application in neurological disorders, cancer, and autoimmune diseases.
View original content to download multimedia:https://www.prnewswire.com/news-releases/biohavens-taldefgrobep-alfa-receives-fda-fast-track-designation-for-spinal-muscular-atrophy-301751239.html
SOURCE BIOHAVEN LTD
Biohaven's spinal muscular atrophy therapy gets FDA fast track status
Feb. 21, 2023 9:10 AM ET
By: Ravikash, SA News Editor
- The U.S. Food and Drug Administration (FDA) granted fast track designation to Biohaven (NYSE:BHVN) medicine taldefgrobep alfa to treat spinal muscular atrophy (SMA).
- https://seekingalpha.com/news/3938384-biohavens-spinal-muscular-atrophy-therapy-gets-fda-fast-track-status
- Biohaven Ltd. (BHVN)
- https://www.biohaven.com/
(RSV) vaccine candidate PF-06928316 or RSVpreF
(RSV) vaccine candidate PF-06928316 or RSVpreF
(RSV) vaccine candidate PF-06928316 or RSVpreF
U.S. FDA Accepts Biologics License Application for Pfizer’s Respiratory Syncytial Virus Maternal Vaccine Candidate for Priority Review
Tuesday, February 21, 2023 - 06:45am
- U.S. FDA has set an action date for August 2023. If approved, RSVpreFwould be the first vaccine for administration to pregnant individuals to help protect against the complications of RSV disease in infants from birth through six months
- This action follows the recent acceptance of the Marketing Authorization Application (MAA) for Pfizer’s RSV vaccine candidate by the European Medicines Agency (EMA) under accelerated assessment for both older adults and maternal immunization
- The maternal immunization regulatory filings are supported by results of the pivotal Phase 3 trial MATISSE, which will be presented to the CDC’s Advisory Committee on Immunization Practices (ACIP), as well as during the ReSViNET Foundation’s 2023 Global Conference, on February 23
NEW YORK--(BUSINESS WIRE)-- Pfizer Inc. (NYSE:PFE) today announced that the U.S. Food and Drug Administration (FDA) has accepted for review a Biologics License Application (BLA) for its respiratory syncytial virus (RSV) vaccine candidate PF-06928316 or RSVpreF for the prevention of medically attended lower respiratory tract illness (MA-LRTI) and severe MA-LRTI caused by RSV in infants from birth up to six months of age by active immunization of pregnant individuals. This decision follows the FDA’s Breakthrough Therapy Designation for RSVpreF in March 2022. The FDA has accepted the BLA for priority review and has set a Prescription Drug User Fee Act (PDUFA) action date of August 2023.
“If approved, RSVpreF would help protect infants at their first breath from the devastating effects of this infectious disease, which though well-known, has been particularly evident throughout this RSV season,” said Annaliesa Anderson, Ph.D., Senior Vice President and Chief Scientific Officer, Vaccine Research & Development, Pfizer. “We look forward to progressing the review of Pfizer’s RSV maternal vaccine candidate with the FDA and other regulatory authorities, given its significant potential to positively contribute to global health in the prevention of RSV in infants.”
In addition, the European Medicines Agency (EMA) has accepted Pfizer’s marketing authorization application (MAA) under accelerated assessment for its RSV vaccine candidate for both older adults and maternal immunization to help protect infants. A decision is expected in the second half of 2023.
The maternal immunization regulatory submission is supported by the positive top-line results from MATISSE (MATernal Immunization Study for Safety and Efficacy), a Phase 3 clinical trial evaluating the efficacy, safety, and immunogenicity of RSVpreF against MA-LRTI and severe MA-LRTI in infants born to healthy women vaccinated during pregnancy. These data will be presented on February 23 to the U.S. Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices (ACIP) and, separately, during the ReSViNET Foundation’s 2023 Global Conference on Novel RSV Preventive and Therapeutic Interventions.
Additional ACIP Presentations
During the ACIP meeting on February 22-23, the company also will present positive Phase 3 results supporting the regulatory filings of Pfizer’s pentavalent meningococcal vaccine (MenABCWY) candidate, as well as Pfizer’s 20-valent pneumococcal conjugate vaccine (20vPnC) candidate for pediatric use.
In December 2022, Pfizer announced that the FDA had accepted for review a BLA for its MenABCWY candidate for the prevention of meningococcal disease caused by the most common serogroups in individuals 10 through 25 years of age. The PDUFA goal date for a decision by the FDA on the MenABCWY application is in October 2023. If approved and recommended, MenABCWY could help simplify the meningococcal vaccination schedule and provide the broadest serogroup coverage of any meningococcal vaccine. Top-line results from a randomized, active-controlled, and observer-blinded Phase 3 trial of Pfizer’s pentavalent meningococcal vaccine candidate (NCT04440163) were previously announced in September 2022.
Similarly, in January 2023, Pfizer announced that the FDA had granted priority review to a supplemental BLA for its 20vPnC candidate for the prevention of invasive pneumococcal disease (IPD) caused by the 20 Streptococcus pneumoniae (pneumococcus) serotypes contained in the vaccine in infants and children 6 weeks through 17 years of age, and for the prevention of otitis media caused by seven of the 20 Streptococcus pneumoniae serotypes contained in the vaccine. The PDUFA goal date for the FDA’s decision on the 20vPnC application is in April 2023. If approved, 20vPnC would have the potential to cover more of the clinically significant remaining burden of infant pneumococcal disease than any other available pneumococcal conjugate vaccine. In August 2022 Pfizer announced top-line results from its pivotal U.S. Phase 3 study (NCT04382326), which support the FDA application.
Burden of RSV
RSV is a contagious virus and a common cause of respiratory illness.1 The virus can affect the lungs and breathing passages of an infected individual and can potentially cause severe illness in young infants, older adults, and individuals with certain chronic medical conditions.2,3,4
Among children younger than five years old in the U.S., RSV infections account for approximately 2.1 million outpatient visits and 58,000 hospitalizations each year.5,6 Virtually all children get an RSV infection by the time they are 2 years old7, and RSV is a leading cause of hospitalization in children <1 year of age.8 Worldwide, RSV results in the death of approximately 102,000 children annually, with about half of those in infants less than six months old and the vast majority in developing countries.9,10
RSV bronchiolitis is the leading cause of infant hospitalization due to viral respiratory illness, characterized by respiratory distress that can result in death. There is no specific treatment for RSV, only supportive care measures like oxygen and fluids. Currently, there is no vaccine to help prevent RSV in the U.S., leaving most infants without protection. The only available preventive agent is recommended for use among the highest-risk infants in limited settings as a monthly injection with five doses administered during the RSV season.
Among adults 65 years and older, RSV infections account for approximately 60,000–160,000 hospitalizations and 6,000–10,000 deaths each year in the U.S. alone.11,12,13,14,15,16,17,18 There are currently no targeted prophylactic, therapeutic, or vaccine options for RSV in older adults, and treatment is limited to offering supportive care for adults with the illness.
About RSVpreF
Pfizer’s investigational RSV vaccine candidate builds on foundational basic science discoveries including those made at the National Institutes of Health (NIH), which detailed the crystal structure of prefusion F, a key form of the viral fusion protein (F) that RSV uses to enter human cells. The NIH research showed that antibodies specific to the prefusion form were highly effective at blocking virus infection, suggesting a prefusion F-based vaccine may confer optimal protection against RSV. After this important discovery, Pfizer tested numerous versions of a stabilized prefusion F protein and identified a candidate that elicited a strong anti-viral immune response in pre-clinical evaluations. The bivalent vaccine candidate is composed of equal amounts of recombinant RSV prefusion F from subgroups A and B.
Pfizer is currently the only company with a maternal RSV vaccine candidate in late-stage development to help protect against RSV. In December 2022, Pfizer announced that the FDA had granted priority review to a biologics license application for RSVpreF for the prevention of RSV disease in older adults.
About the Pentavalent Meningococcal Vaccine Candidate (MenABCWY)
Pfizer’s pentavalent meningococcal vaccine candidate combines the components from its two licensed meningococcal vaccines, Trumenba® (meningococcal group B vaccine) and Nimenrix® (meningococcal groups A, C, W-135, and Y conjugate vaccine); approvals of Nimenrix® and Trumenba® vary by country. Together, the 5 serogroups included in MenABCWY are responsible for the majority of currently circulating meningococcal disease globally.19
INDICATIONS FOR TRUMENBA® IN THE U.S.
- Trumenba® is a vaccine indicated for individuals 10 through 25 years of age for active immunization to prevent invasive disease caused by Neisseria meningitidis group B
INDICATION FOR NIMENRIX® IN THE E.U.
- Nimenrix® is a vaccine indicated for individuals six weeks of age and older for active immunization to prevent invasive disease caused by Neisseria meningitidis groups A, C, W-135 and Y
View source version on businesswire.com: https://www.businesswire.com/news/home/20230221005199/en/
Source: Pfizer Inc.
Pfizer wins priority review for maternal RSV vaccine candidate
Feb. 21, 2023 8:52 AM ET
By: Dulan Lokuwithana, SA News Editor2 Comments
Pfizer (NYSE:PFE) announced Tuesday that the FDA accepted its Biologics License Application (BLA) for its respiratory syncytial virus (RSV) vaccine candidate PF-06928316 for priority review targeting pregnant women for the prevention of RSV in infants.
Beyfortus (nirsevimab)
(RSV) vaccine candidate PF-06928316 or RSVpreF
VLA1553 (Chikungunya Vaccine )
ReSViNet 2023 data reinforce AstraZeneca’s commitment to help prevent Respiratory Syncytial Virus in infants
PUBLISHED21 February 2023
21 February 2023 07:00 GMT
Beyfortus continues to demonstrate consistent protection against
RSV disease through the RSV season
New Canadian analysis demonstrates Synagis to be highly cost-effective in
29-35 weeks gestational age infants
AstraZeneca will showcase new data across its Vaccines and Immune Therapies Respiratory Syncytial Virus (RSV) portfolio at the 7th Respiratory Syncytial Virus Foundation (ReSViNET) Conference in Lisbon, Portugal from 22-24 February 2023, reinforcing its commitment to help protect infants from RSV. The Company is set to present five abstracts and posters at the event, including new data featuring Beyfortus (nirsevimab) and Synagis (palivizumab).
Iskra Reic, Executive Vice President, Vaccines and Immune Therapies, AstraZeneca, said: “I am proud of AstraZeneca’s commitment to respiratory syncytial virus (RSV) and our continued focus on innovating antibodies to provide protection to the most vulnerable. We believe that Beyfortus has the potential to transform the medical community’s approach to preventing RSV infections in infants, and this is of particular importance given the recent surges of the virus amongst infants this past winter season.”
Underscoring the continued need for RSV protection
AstraZeneca is working with the global clinical community to advance the understanding of RSV and is partnering with the ReSViNET Foundation to create the first global RSV surveillance dashboard set to launch in March 2023. RSV is a highly contagious virus that causes respiratory illness in infants, including lung infections such as bronchiolitis and pneumonia.1 This seasonal respiratory virus is the most common cause of lower respiratory tract infections and a leading cause of hospitalisation in infants.1-5
Dr. Louis Bont, Pediatrician Infectologist at the Wilhelmina Children’s Hospital in the University Medical Center Utrecht, The Netherlands, and the founder and chairman of ReSViNET, said: “The ReSViNET Foundation’s new dashboard will make it easier and more accessible to track worldwide changes in RSV seasonality, helping clinicians to protect babies and prevent the rise in hospitalisations that RSV can cause.”
Pursuing a breakthrough for broad RSV prevention
AstraZeneca is presenting the safety and efficacy findings from the full cohort of the Phase III MELODY clinical trial investigating Beyfortus in healthy late preterm and term infants (35 weeks gestational age or greater) entering their first RSV season. These data reinforce Beyfortus’ consistent efficacy across endpoints and studies with approximately 70-80% efficacy against medically attended RSV lower respiratory tract infections vs placebo, including hospitalisations.6-10
New cost effectiveness data for high-risk infant protection
Synagis continues to build on 25 years of real-world usage with a new cost effectiveness analysis being presented at ReSViNet. This analysis is the first to incorporate the International Risk Scoring Tool, which helps clinicians identify pre-term infants with the highest risk of hospitalisation.
RSV
RSV is the most common cause of lower respiratory infections, including bronchiolitis and pneumonia in infants.1 It is also a leading cause of hospitalisation in all infants.1-5 Globally, in 2019, there were approximately 33 million cases of acute lower respiratory infections leading to more than three million hospitalisations, and it was estimated that there were 26,300 in-hospital deaths of children younger than five years.11 RSV-related direct medical costs, globally – including hospital, outpatient and follow-up care – were estimated at €4.82 billion in 2017.12
Beyfortus (nirsevimab)
Beyfortus is a single dose long-acting antibody, developed and commercialised in partnership by AstraZeneca and Sanofi using AstraZeneca’s YTE technology. It is designed to protect infants entering or during their first RSV season and for children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season.
Beyfortus has been developed to offer newborns and infants direct RSV protection via an antibody to help prevent LRTI caused by RSV. Monoclonal antibodies do not require the activation of the immune system to help offer timely, rapid and direct protection against disease.14
Beyfortus has been granted regulatory and other designations to facilitate expedited development by several major regulatory agencies around the world. These include Breakthrough Therapy Designation by the China Center for Drug Evaluation under the National Medical Products Administration; Breakthrough Therapy Designation from the US Food and Drug Administration; access granted to the European Medicines Agency (EMA) PRIority Medicines (PRIME) scheme; and named “a medicine for prioritized development” under the Project for Drug Selection to Promote New Drug Development in Pediatrics by the Japan Agency for Medical Research and Development (AMED). In November 2022, Beyfortus was approved by the European Commission and by the UK Medicines and Healthcare products Regulatory Agency (MHRA).15-16
Sanofi Alliance
In March 2017, AstraZeneca and Sanofi announced an agreement to develop and commercialise nirsevimab. Under the terms of the agreement, AstraZeneca leads all development and manufacturing activities, and Sanofi leads commercialisation activities and records revenue. Under the terms of the global agreement, Sanofi made an upfront payment of €120m, has paid a development milestone of €30m and will pay up to a further €465m upon achievement of certain development and sales-related milestones. The two companies share costs and profits. Revenue from the agreement is reported as Collaboration Revenue in the Company’s financial statements.
Sobi agreement
Related, in November 2018, AstraZeneca agreed to sell US commercial rights for Synagis (palivizumab) to Swedish Orphan Biovitrum AB (publ) (Sobi) in addition to the right to participate in payments that may be received by AstraZeneca from the US profits or losses for nirsevimab. Under the agreement, AstraZeneca received upfront consideration, non-contingent payments for nirsevimab during 2019-2021, and following the FDA’s acceptance of the Biologics License Application (BLA) filing for nirsevimab, will receive a $175m cash payment. AstraZeneca is also entitled to receive certain other milestone payments for nirsevimab, including a $90m cash payment following the date on which BLA approval in the US occurs. AstraZeneca will continue to manufacture and supply nirsevimab globally and is entitled to an additional royalty from Sobi if profits from nirsevimab in the US exceed a pre-specified level.
Synagis (palivizumab)
Synagis (palivizumab) is an RSV F protein inhibitor monoclonal antibody indicated for the prevention of serious lower respiratory tract disease caused by RSV in paediatric patients with a history of premature birth (less than or equal to 35 weeks gestational age) and who are 6 months of age or younger at the beginning of the RSV season, with bronchopulmonary dysplasia (BPD) that required medical treatment within the previous 6 months and who are 24 months of age or younger at the beginning of the RSV season, or with hemodynamically significant congenital heart disease (CHD) and who are 24 months of age or younger at the beginning of the RSV season.13
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.
AstraZeneca, Sanofi's RSV therapy Beyfortus for infants shows 'consistent protection' in trial
Feb. 21, 2023 5:01 AM ET
Swedish Orphan Biovitrum AB (publ) (BIOVF), SNY, AZN
By: Ravikash, SA News Editor
AstraZeneca (NASDAQ:AZN) and Sanofi's (NASDAQ:SNY) antibody therapy Beyfortus continues to show consistent protection against Respiratory Syncytial Virus (RSV) disease through the RSV season in infants, the British drugmaker said on Tuesday.
Swedish Orphan Biovitrum AB (publ) (BIOVF), SNY, AZN
VLA1553 (Chikungunya Vaccine )
VLA1553 (Chikungunya Vaccine )
VLA1553 (Chikungunya Vaccine )
FDA Accepts Valneva’s Chikungunya Vaccine License Application for Priority Review
February 20, 2023
Saint-Herblain (France),
February 20, 2023 –
Valneva SE (Nasdaq: VALN; Euronext Paris: VLA), a specialty vaccine company, today announced that the U.S. Food and Drug Administration (FDA) has completed a filing review of its Biologics License Application for Valneva’s single-shot chikungunya vaccine candidate VLA1553 and has determined that the application is sufficiently complete to permit a substantive review. The review classification is Priority.
VLA1553 has been assigned a Prescription Drug User Fee Act (PDUFA) review goal date at the end of August 2023, which is the date by which the FDA intends to take action on the application. The FDA’s acknowledgement of filing does not mean that a license will be granted, nor does it represent any evaluation of the adequacy of the data submitted.
About Chikungunya
Chikungunya is a mosquito-borne viral disease caused by the chikungunya virus (CHIKV), a Togaviridae virus, transmitted by Aedes mosquitoes. Chikungunya virus often causes sudden large outbreaks with high attack rates, affecting one-third to three-quarters of the population in areas where the virus is circulating. There are no preventive vaccines or effective treatments available and, as such, chikungunya is considered to be a major public health threat. As of July 2022, there were more than 3 million reported cases in the Americas[1] and the economic impact is considered to be significant. The medical and economic burden is expected to grow as the CHIKV primary mosquito vectors continue to spread geographically. Infection leads to symptomatic disease in up to 97% of humans after three to seven days following the mosquito bite. While mortality with CHIKV is low, morbidity is high. Clinical symptoms include acute onset of fever, debilitating joint and muscle pain, headache, nausea, rash and chronic arthralgia. It is estimated that over three quarters of the world’s population live in areas at-risk of CHIKV transmission[2]. High risk areas of infection are places where chikungunya virus-carrying mosquitos are currently endemic, including the Americas, parts of Africa, and Southeast Asia.
About VLA1553
VLA1553 is a live-attenuated, single dose investigational vaccine candidate targeting the chikungunya virus, which has spread to over 100 countries. It has been designed by deleting a part of the chikungunya virus genome.
To make VLA1553 more accessible to Low- and Middle-Income Countries (LMIC), Valneva and Instituto Butantan in Brazil signed an agreement in January 2021 for the development, manufacturing and marketing of VLA1553[3]. The collaboration falls within the framework of the agreement signed between CEPI and Valneva in July 2019[4], which provides funding of up to $24.6 million with support from the European Union’s Horizon 2020 program.
Valneva reported final data from the pivotal Phase 3 trial of VLA1553 in March 2022[5], final lot-to-lot consistency results in May 2022[6] and positive twelve-month persistence data in December 2022[7].
If approved, VLA1553 would expand Valneva’s existing commercial vaccines portfolio and as such, Valneva intends to commercialize this vaccine, leveraging its existing manufacturing and commercial operations.
About Valneva SE
Valneva is a specialty vaccine company focused on the development, manufacturing and commercialization of prophylactic vaccines for infectious diseases with significant unmet medical need. The Company takes a highly specialized and targeted approach to vaccine development and then applies its deep understanding of vaccine science to develop prophylactic vaccines addressing these diseases. Valneva has leveraged its expertise and capabilities both to commercialize three vaccines and to rapidly advance a broad range of vaccine candidates into and through the clinic, including candidates against the chikungunya virus and Lyme disease.
Valneva's single-shot chikungunya vaccine VLA1553 gets FDA priority review
Feb. 20, 2023 5:35 AM ET
By: Ravikash, SA News Editor
- The U.S. Food and Drug Administration (FDA) granted priority review to Valneva (NASDAQ:VALN) application seeking approval of single-shot chikungunya vaccine candidate VLA1553.
- https://seekingalpha.com/news/3937917-valnevas-single-shot-chikungunya-vaccine-vla1553-gets-fda-priority-review
- Valneva SE (VALN)
- https://valneva.com/research-development/chikungunya/
Zavegepant
VLA1553 (Chikungunya Vaccine )
Zavegepant
Pfizer Announces The Lancet Neurology Has Published Phase 3 Data for Zavegepant for the Acute Treatment of Migraine in Adults
Thursday, February 16, 2023 - 06:45am
- Zavegepant is the first and only calcitonin gene-related peptide (CGRP) receptor antagonist in development as an intranasal formulation studied in a Phase 3 trial
NEW YORK--(BUSINESS WIRE)-- Pfizer Inc. (NYSE: PFE) today announced publication of results in The Lancet Neurologyfrom the Phase 3 pivotal clinical trial of zavegepant, an investigational calcitonin gene-related peptide (CGRP) receptor antagonist nasal spray for the acute treatment of migraine. The study met its co-primary endpoints, showing that a single 10 mg dose of zavegepant was more effective than placebo for both pain freedom and freedom from the most bothersome symptom (MBS) at two hours post-dose. Additionally, zavegepant demonstrated relief from migraine pain in 15 minutes, with relief lasting up to 48 hours for many patients. Zavegepant was well tolerated, and there were no serious adverse events reported in treated participants.
“The results from this study demonstrate zavegepant’s potential as an effective acute nasal spray treatment for migraine, a neurological disorder that affects more than one billion people worldwide,” said Richard B. Lipton, M.D., Lead Author, Department of Neurology at the Albert Einstein College of Medicine. “This was the first Phase 3 clinical trial of a non-oral CGRP receptor antagonist developed for the acute treatment of migraine in adults. With this evidence of sustained treatment benefits, good tolerability and an alternative administration method, I believe zavegepant has the potential to fill an important gap in the available options for the acute treatment of migraine.”
In the trial, 1,405 people were randomized to receive a single 10 mg dose of either zavegepant or placebo. Participants historically experienced two to eight moderate or severe migraine attacks per month, and their untreated attacks lasted a mean of 30.8 hours. During the study, participants recorded their migraine headache pain intensity based on a four-point scale, identified their current MBS associated with migraine (selected from phonophobia, photophobia or nausea) and recorded their level of functional disability immediately before dosing the treated attack and at various intervals post-dose.
Zavegepant was demonstrated to be effective in the acute treatment of migraine, as measured by superiority to placebo on the co-primary efficacy endpoints of pain freedom (24% vs 15%, P<0·0001) and freedom from the MBS (40% vs 31%, P=0·0012) at two hours post-dose. Additionally, zavegepant was more effective than placebo on 13 of the 17 secondary endpoints, including treatment benefits for pain relief beginning as early as 15 minutes and sustained pain relief from two through 48 hours post-dose. On the 14th endpoint, return to normal function at 15 minutes post-dose, the difference between zavegepant and placebo was not significant. Consequently, in keeping with the analysis plan, the remaining secondary endpoints were not formally tested. Treatment with zavegepant was also associated with higher rates of return to normal functional ability at 30 minutes post treatment and two hours.
Zavegepant was well tolerated in this study. The most common adverse events (AE) in either treatment group (≥2%) were dysgeusia (an altered sense of taste), occurring in 20.5% of zavegepant patients as compared to 4.7% of patients on placebo, nasal discomfort, occurring in 3.7% of zavegepant patients as compared to 0.8% of patients on placebo, and nausea, occurring in 3.2% of zavegepant patients and 1.1% of patients on placebo. The AE safety profile was consistent with earlier studies of zavegepant. There were no serious AEs reported in treated participants, and no signal of hepatotoxicity due to zavegepant was identified in the trial.
“The intranasal formulation for zavegepant embodies breakthrough innovation in patient-centric drug development,” said James Rusnak, M.D., Ph.D., Senior Vice President, Chief Development Officer, Internal Medicine and Hospital, Global Product Development, Pfizer. “If approved by the FDA, zavegepant has the potential to be a significant new treatment option for people with migraine, particularly those who desire fast-acting relief or would benefit from an alternative delivery method. We are excited by the momentum the publication of these study results offers, as we anticipate potentially bringing a new medical breakthrough to millions of people suffering from migraine in the U.S.”
About Zavegepant
Zavegepant is a third generation, high affinity, selective and structurally unique, small molecule CGRP receptor antagonist and the only CGRP receptor antagonist in clinical development with both intranasal and oral formulations. The New Drug Application (NDA) was filed for intranasal zavegepant with the U.S. Food and Drug Administration for the acute treatment of migraine in adults. The Prescription Drug User Fee Act (PDUFA) goal date for completion of the FDA review of the NDA is set for 1Q2023.
About Migraine
Nearly 40 million people in the U.S. suffer from migraine1 and the World Health Organization classifies migraine as one of the 10 most disabling medical illnesses.2 Migraine is characterized by debilitating attacks lasting four to 72 hours with multiple symptoms, including pulsating headaches of moderate to severe pain intensity that can be associated with nausea or vomiting, and/or sensitivity to sound (phonophobia) and sensitivity to light (photophobia).3
About CGRP Receptor Antagonism
Small molecule CGRP receptor antagonists represent a novel class of drugs for the treatment of migraine. For acute treatment, this unique mode of action potentially offers an alternative to other agents, particularly for patients who have contraindications to the use of triptans or who have a poor response to triptans or are intolerant to them. CGRP signal-blocking therapies have not been associated with medication overuse headache (MOH) or rebound headaches which can limit the clinical utility of other acute treatments.
View source version on businesswire.com: https://www.businesswire.com/news/home/20230216005209/en/
Source: Pfizer Inc.
Pfizer migraine nasal spray drug zavegepant meets phase 3 goals
Feb. 16, 2023 7:15 AM ET
By: Ravikash, SA News Editor2 Comments
Pfizer (NYSE:PFE) said results from a phase 3 trial of nasal spray zavegepant for the acute treatment of migraine were published in The Lancet Neurology.
Pfizer inherited zavegepant from its ~$11.6B acquisition of migraine drugmaker Biohaven. The drug is currently under review in the U.S. with an FDA decision expected in Q1 2023.
KIN-3248
VLA1553 (Chikungunya Vaccine )
Zavegepant
Kinnate Biopharma Inc. Receives Fast Track Designation from the U.S. Food and Drug Administration for KIN-3248, an Investigational Pan-FGFR Inhibitor
February 14, 2023 at 4:05 PM EST
SAN FRANCISCO and SAN DIEGO, Feb. 14, 2023 (GLOBE NEWSWIRE) --
Kinnate Biopharma Inc. (Nasdaq: KNTE) (“Kinnate”), a clinical-stage precision oncology company, today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for Kinnate’s investigational pan-FGFR inhibitor, KIN-3248, for the treatment of patients with unresectable, locally advanced or metastatic cholangiocarcinoma (CCA) harboring fibroblast growth factor receptor 2 (FGFR2) gene fusions or other alterations, who have received at least one prior systemic therapy.
Cholangiocarcinoma, also known as bile duct cancer, is a rare condition, often diagnosed when it is advanced. Research has shown that FGFR is an actionable alteration in patients with CCA. FGFRs are tyrosine kinases that play a crucial role in cell proliferation, differentiation, migration and survival. FGFR2 gene fusions or other alterations are identified in approximately 16% of intrahepatic cholangiocarcinoma (ICC) tumors.
Fast Track is a process designed by the FDA to facilitate the development and expedite the review of drugs to treat serious conditions and fulfill an unmet medical need. A therapeutic candidate that receives Fast Track designation is eligible for more frequent interactions with the FDA to discuss the candidate’s development plan, and if relevant criteria are met, for Accelerated Approval and Priority Review.
About KIN-3248
KIN-3248 is an irreversible, small molecule pan-FGFR inhibitor designed to address primary FGFR2 and FGFR3 oncogenic alterations, including those predicted to drive acquired resistance to current FGFR-targeted therapies, such as gatekeeper, molecular brake, and activation loop mutations observed in cancers such as ICC and urothelial carcinoma (UC). In preclinical studies, KIN-3248 demonstrated inhibitory activity across a wide range of clinically relevant mutations that drive primary disease and acquired resistance to other FGFR inhibitors.
The KN-4802 clinical trial (NCT05242822) is an ongoing multi-center, open-label, two-part study of approximately 120 patients to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of KIN-3248 in adults with advanced tumors harboring FGFR2 and/or FGFR3 gene alterations. In dose escalation (Part A), the trial will determine the recommended dose and schedule of KIN-3248 for further evaluation in patients with FGFR2 and/or FGFR3 gene alteration-driven cancers. Dose expansion (Part B) will assess the safety and efficacy of KIN-3248 at the recommended dose and schedule in FGFR inhibitor naïve and FGFR inhibitor pretreated patients with cancers driven by FGFR2 and/or FGFR3 gene alterations, including ICC, UC, and other advanced or metastatic solid tumors in adults.
This trial is currently enrolling across multiple sites in the U.S. and Taiwan, with additional sites expected globally. Initial dose escalation data is anticipated in the second half of 2023.
The company previously announced that a poster presentation of the design and rationale of the KN-4802 clinical trial will be presented at the upcoming American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium. Details are included below.
ASCO Genitourinary Cancers Symposium, February 16-18, 2023
Title: First-in-Human Phase 1/1b Study Evaluating KIN-3248, a Next‑Generation, Irreversible Pan-FGFR Inhibitor, in Patients With Advanced Urothelial Carcinoma and Other Solid Tumors Harboring FGFR2 and/or FGFR3 Gene Alterations
Author: Benjamin Garmezy, MD
Abstract Number: TPS593
Poster Board: P16
Session Type and Track: Trials in Progress Poster Session, Urothelial Carcinoma
Session Date: February 17, 2023, 12:30 p.m. PT / 3:30 p.m. ET
For additional information, visit the ASCO Meeting webpage: https://conferences.asco.org.
About Kinnate Biopharma Inc.
Kinnate Biopharma Inc. is a clinical-stage precision oncology company focused on expanding on the promise of targeted therapies for those battling cancer. The company is developing medicines for known oncogenic drivers where there are no approved targeted drugs and to overcome the limitations of marketed cancer therapies, such as non-responsiveness or acquired and intrinsic resistance. Kinnate has two lead clinical programs being studied in solid tumors with RAF, NRAS and FGFR-driven alterations, and is rapidly progressing a pipeline of additional small molecule drug candidates as part of the Kinnate Discovery Engine. The company is driven by the urgency and knowledge that patients are waiting for new, effective cancer medicines. For more information, visit Kinnate.com and follow us on LinkedIn.
Kinnate Biopharma gets FDA fast track designation for its bile duct cancer treatment
Feb. 14, 2023 5:26 PM ET
By: Anuron Mitra, SA News Editor
- Kinnate Biopharma (NASDAQ:KNTE) on Tuesday said the U.S. Food and Drug Administration (FDA) had granted a fast track designation to its inhibitor KIN-3248 for the treatment of bile duct cancer.
- https://seekingalpha.com/news/3936095-kinnate-biopharma-gets-fda-fast-track-designation-for-its-bile-duct-cancer-treatment
- Kinnate Biopharma Inc. (KNTE)
- https://www.kinnate.com/science-and-pipeline/
- https://www.kinnate.com/
biotecHOPE™ 2023
Povorcitinib (INCB54707)
Povorcitinib (INCB54707)
Povorcitinib (INCB54707)
Incyte Announces 52-Week Results From Phase 2 Study Evaluating Povorcitinib (INCB54707) In Patients With Hidradenitis Suppurativa
February 10, 2023 at 8:20 AM EST
- Results from open-label extension period of the Phase 2 trial demonstrate that longer-term treatment with povorcitinib 75 mg resulted in sustained and durable efficacy across all treatment arms
- Data featured as an oral presentation at the European Hidradenitis Suppurativa Foundation conference
- Hidradenitis suppurativa (HS) is a chronic and debilitating inflammatory skin condition characterized by painful nodules and abscesses that can lead to irreversible tissue destruction and scarring1
WILMINGTON, Del.--(BUSINESS WIRE)--Feb. 10, 2023-- Incyte (Nasdaq:INCY) today announced new 52-week results from a Phase 2 study evaluating the efficacy and safety of povorcitinib (formerly INCB54707), an oral JAK1 inhibitor, in adult patients with hidradenitis suppurativa (HS). These data were presented as an oral presentation (Abstract #258) at the 12th Conference of the European Hidradenitis Suppurativa Foundation, held from February 8-10, 2023, in Florence, Italy.
The study previously met its primary endpoint, demonstrating that at Week 16 – the double-blind, placebo-controlled portion of the study – patients receiving povorcitinib once daily (QD) had significantly greater decreases from baseline in Abscess and Inflammatory Nodule (AN) count versus placebo (least squares mean change, −2.5 [0.9], placebo vs. −5.2 [0.9], P=0.0277, povorcitinib 15 mg; −6.9 [0.9], P=0.0006, povorcitinib 45 mg; −6.3 [0.9], P=0.0021), povorcitinib 75 mg)2.
New results at Week 52, which include the 36-week open-label extension period during which all patients received povorcitinib 75 mg once daily (QD), show that average efficacy was sustained for all treatment arms following the switch to povorcitinib 75 mg QD (mean change in AN count from Day 1 baseline at Week 52 was −5.7 [7.3], placebo→75 mg; −8.4 [5.6], 15→75 mg; −10.4 [14.6], 45→75 mg; and −5.4 [5.6], 75 mg). Importantly, povorcitinib also demonstrated durable efficacy at Week 52 in high-threshold outcomes, as evidenced by 22-29% of patients achieving HS Clinical Response 100 (HiSCR100), which is defined as a 100% reduction from baseline in total AN count with no increase from baseline in abscess or draining tunnel count.
Povorcitinib was generally well tolerated and the safety profile was consistent with previously-reported data. The most common treatment-emergent adverse events (TEAEs) at Week 52 (n=174) were COVID-19 (21.3%), acne (11.5%), upper respiratory tract infection (10.9%), headache (5.7%), nasopharyngitis (5.7%), urinary tract infection (5.7%) and increased blood creatine kinase (CK) (5.2%). In total, six patients (3.4%) experienced a TEAE that led to treatment discontinuation. No fatal TEAEs were observed.
“HS is a chronic, progressive and debilitating condition for which there is no cure. We are encouraged by these Phase 2 data and believe they reinforce the potential of povorcitinib to be a safe and efficacious treatment for HS that is tolerable with longer-term administration, even at the higher doses,” said Kurt Brown, M.D., Global Program Head, Povorcitinib, and Associate Vice President, Drug Development, Inflammation & AutoImmunity, Incyte. “Despite the available treatments for HS, no uniformly-effective therapy has been found, underscoring the need for additional options. We look forward to continuing to progress the development of povorcitinib through our ongoing Phase 3 trial in patients with moderate-to-severe HS.”
“Given the nature of HS, which presents with persistent, painful nodules and abscesses, this immune-mediated skin condition often has a severe impact on a patient’s quality of life,” said Joslyn Kirby, M.D., M.S., M.Ed., Associate Professor and Vice Chair for Education, Department of Dermatology at Penn State Health. “I am encouraged by these promising results suggesting that povorcitinib may be a favorable oral treatment option that could provide substantial relief from common HS symptoms for patients.”
This presentation will be made available for registered participants on the EHSF website at https://www.eventclass.org/contxt_ehsf2023/scientific/online-program/session?s=S-09#e268 and can be accessed until August 31, 2023.
About Hidradenitis Suppurativa
Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition characterized by painful nodules and abscesses that can lead to irreversible tissue destruction and scarring.1 Over-activity of the JAK/STAT signaling pathway is believed to drive inflammation involved in the pathogenesis and progression of HS3. More than 150,000 patients in the U.S. are estimated to have moderate to severe HS4. Given the debilitating nature of condition, it can have a profoundly negative effect on patients’ quality of life5.
About the Phase 2 Study (NCT04476043)
This Phase 2, randomized, double-blind, placebo-controlled, dose-ranging study is evaluating the efficacy and safety of povorcitinib (formerly INCB54707) in adult patients with hidradenitis suppurativa (HS).
The first part of the study spanned 16 weeks and enrolled 209 adults (aged 18-75 years) who were randomized 1:1:1:1 to povorcitinib 15 mg once daily (QD; n=52), 45 mg QD (n=52), 75 mg QD (n=53) or placebo (n=52). Eligible patients had an HS (Hurley stage I, II or III) disease duration of ≥3 months prior to screening, and active HS in at least two distinct anatomical areas. The primary efficacy endpoint is mean change from baseline in Abscess and Inflammatory Nodule (AN) count at Week 16. The key secondary endpoint is percentage of patients achieving HS Clinical Response (HiSCR; ≥50% reduction from baseline in AN count with no increase in number of abscesses or draining tunnels) at Week 16.
The second part of the study, the open-label extension (OLE) period, spanned an additional 36 weeks (52 weeks total) and included patients enrolled in the first part of the study. All OLE patient participants (n=174) received treatment with povorcitinib 75 mg QD. After Week 52, patients who completed baseline, Week 16 and Week 52 assessments could continue to receive open-label treatment with povorcitinib 75 mg QD for an additional 48 weeks.
Endpoints at Week 52 include mean change from baseline in AN count, HiSCR and HiSCR75/90/100 (≥75%/90%/100% reduction from baseline in AN count with no increase in the number of abscesses or draining tunnels), HS flare occurrence, mean change from baseline in International Hidradenitis Suppurativa Severity Score System (IHS4) and IHS455/75/90/100 (≥55%/75%/90%/100% reduction from baseline in IHS4 score). Safety of povorcitinib was assessed by the frequency and severity of treatment-emergent adverse events (TEAEs).
For more information about this Phase 2 study, please visit https://clinicaltrials.gov/ct2/show/NCT04476043.
About Povorcitinib (INCB54707)
Povorcitinib (INCB54707) is an oral small-molecule JAK1 inhibitor currently in Phase 2 clinical trials for hidradenitis suppurativa (HS), vitiligo and prurigo nodularis. A Phase 3 study in HS is also ongoing.
About Incyte
Incyte is a Wilmington, Delaware-based, global biopharmaceutical company focused on finding solutions for serious unmet medical needs through the discovery, development and commercialization of proprietary therapeutics. For additional information on Incyte, please visit Incyte.com and follow @Incyte.
Incyte skin disorder drug shows durable efficacy in 1 year data from mis-stage trial
Feb. 10, 2023 9:17 AM ET
By: Ravikash, SA News Editor
Incyte (NASDAQ:INCY) said an extension period of a phase 2 trial showed that longer-term treatment with povorcitinib 75 mg resulted in sustained and durable efficacy in patients with a type of skin condition called Hidradenitis suppurativa (HS).
Rigosertib
Povorcitinib (INCB54707)
Povorcitinib (INCB54707)
Feb 07, 2023
Onconova Therapeutics Announces Additional Clinical Data Demonstrating Rigosertib’s Monotherapy Activity In RDEB-Associated Squamous Cell Carcinoma
Two of two evaluable participants in an ongoing investigator-sponsored program of rigosertib in RDEB-associated squamous cell carcinoma (SCC) have achieved a complete response of all cancerous skin lesions
First evaluable participant has been in complete remission with no signs of metastatic disease for >18 months; the second patient has achieved a complete response in all squamous cell skin lesions following four cycles of treatment and remains on therapy with additional scans to follow to evaluate metastatic disease
Onconova plans to review initial data with regulators to gain insights on the optimal regulatory pathway for rigosertib in RDEB-associated SCC, an ultra-rare and invariably fatal condition
NEWTOWN, Pa., Feb. 07, 2023 (GLOBE NEWSWIRE) -- Onconova Therapeutics, Inc. (NASDAQ: ONTX), (“Onconova”), a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer, today announced that the second of two evaluable participants in an investigator-initiated Phase 2 program evaluating rigosertib monotherapy in advanced squamous cell carcinoma complicating recessive dystrophic epidermolysis bullosa (RDEB-associated SCC) achieved a complete response of all cancerous skin lesions following 4 treatment cycles and remains on oral rigosertib.
The Company previously announced that the RDEB-associated SCC program’s first evaluable participant achieved a RECIST-defined complete response. Both of the program’s evaluable participants remain on therapy, with the first participant in complete remission with no signs of metastatic disease for more than 18 months. Rigosertib continues to demonstrate a favorable safety profile in this indication that is similar to that displayed in prior studies in other indications.
“Though from only two participants, the emerging data from this Phase 2 program show rigosertib displaying a level of anti-cancer activity in RDEB-associated SCC that far exceeds what we have seen with currently available treatments,” said Professor Andrew P South from Sidney Kimmel Cancer Center, Thomas Jefferson University. “Given its ultra-orphan nature and the extremely high unmet need in RDEB-associated SCC, I believe regulatory discussions to enable rigosertib’s expeditious advancement to potential approval in this indication are warranted. In parallel, we plan to continue advancing this Phase 2 program and to report more detailed data at a future medical meeting.”
RDEB is caused by insufficient expression of type VII collagen protein, which is responsible for anchoring the skin’s inner layer to its outer layer. This leads to extreme skin fragility as well as chronic blistering and wound formation with recurrent infections in RDEB patients, many of whom go on to develop metastatic squamous cell carcinoma driven by over expression of polo like kinase 1 (PLK1). RDEB-associated SCC tumors show a highly aggressive and early metastasizing course that makes them the primary cause of death for these patients, with a cumulative risk of death of 70% and 78.7% by ages 45 and 55, respectively1,2. RDEB-associated SCC can appear in pediatric patients or in young adults. Currently available treatments such as targeted therapies and conventional chemo- and/or radiotherapy have demonstrated limited response rates and poor durability in RDEB-associated SCC1,3.
Steven M. Fruchtman, M.D., President and Chief Executive Officer of Onconova, commented, “We are pleased to be building on this Phase 2 program’s initial single-patient data with a second participant showing complete resolution of all cancerous skin lesions, with the most recent patient notably seeing this result after only four cycles of therapy. We look forward to reviewing our findings with the FDA to determine the most expeditious regulatory path for rigosertib in RDEB-associated SCC. In addition, these findings may have important implications beyond this orphan indication, as they and prior preclinical data demonstrate rigosertib’s activity against the PLK1 protein. Although the company is focusing its resources mainly on the lead narazaciclib program, preclinical studies exploring rigosertib’s activity in other PLK1-dependent tumors are underway and will hopefully open a broader regulatory path for rigosertib.”
Onconova and a program investigator plan to present more detailed data on the first two evaluable participants from the Phase 2 RDEB-associated SCC program at a future medical meeting. In addition, preclinical data on rigosertib’s mechanism of action have been accepted for presentation at the American Association for Cancer Research (AACR) Targeting RAS Conference, which is taking place in Philadelphia, Pennsylvania from March 5 – 8, 2023.
About Rigosertib
Rigosertib is an investigational product candidate with a multi-faceted mechanism of action targeting proteins containing the RAS binding domain, allowing it to modulate the PI3K and PLK-1 pathways, as well as the tumor immune microenvironment. It is currently being evaluated in multiple investigator-sponsored studies, including a dose-escalation and expansion Phase 1/2a study of oral rigosertib in combination with nivolumab for patients with KRAS+ non-small cell lung cancer refractory to pembrolizumab, the current standard of care for these patients, and a Phase 2 program evaluating rigosertib monotherapy in advanced squamous cell carcinoma complicating recessive dystrophic epidermolysis bullosa.
About Onconova Therapeutics, Inc.
Onconova Therapeutics is a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer. The Company has proprietary targeted anti-cancer agents designed to disrupt specific cellular pathways that are important for cancer cell proliferation.
Onconova’s novel, proprietary multi-kinase inhibitor narazaciclib (formerly ON 123300) is being evaluated in two separate and complementary Phase 1 dose escalation and expansion studies. These trials are currently underway in the United States and China. Based on preclinical and clinical studies of CDK 4/6 inhibitors, Onconova is also planning a combination trial of narazaciclib with estrogen blockade in advanced endometrial cancer, as well as its clinical study in additional indications.
Onconova’s product candidate rigosertib is being studied in multiple investigator-sponsored studies, including a dose-escalation and expansion Phase 1/2a study of oral rigosertib in combination with nivolumab in patients with KRAS+ non-small cell lung cancer, and a Phase 2 program evaluating rigosertib monotherapy in advanced squamous cell carcinoma complicating recessive dystrophic epidermolysis bullosa.
For more information, please visit www.onconova.com.
Onconova Therapeutics posts positive data from squamous cell carcinoma treatment trial
Feb. 07, 2023 9:38 AM ET
Onconova Therapeutics, Inc. (ONTX)
By: Dania Nadeem, SA News Editor
- Onconova Therapeutics (NASDAQ:ONTX) said on Tuesday a Phase 2 trial testing rigosertib monotherapy in advanced squamous cell carcinoma complicating recessive dystrophic epidermolysis bullosa achieved a complete response of all cancerous skin lesions following four treatment cycles.
- https://seekingalpha.com/news/3932872-onconova-therapeutics-posts-positive-data-from-squamous-cell-carcinoma-treatment-trial
- Onconova Therapeutics, Inc. (ONTX)
- https://www.onconova.com/pipeline/
Nipocalimab
Povorcitinib (INCB54707)
Zuranolone (SAGE-217/BIIB125)
Janssen Reports Positive Topline Phase 2 Results for Nipocalimab in Pregnant Individuals at High Risk for Severe Hemolytic Disease of the Fetus and Newborn (HDFN)
Feb 06, 2023
United States
There are currently no approved therapeutics for the treatment of HDFN which, in severe cases, can cause life-threatening anemia in the fetus
SPRING HOUSE, PENNSYLVANIA, February 6, 2023 – The Janssen Pharmaceutical Companies of Johnson & Johnson today announced positive topline results from the proof-of-concept Phase 2 open-label UNITY clinical trial for the treatment of pregnant adults at high risk for severe hemolytic disease of the fetus and newborn (HDFN). HDFN is a serious and rare condition which can cause life-threatening anemia in the fetus. It occurs when the blood types of a pregnant individual and their fetus are incompatible.1The trial met the primary endpoint, with the majority of pregnant patients who received nipocalimab achieving a live birth at or after the gestational age (GA) of 32 weeks, without the need for an intrauterine transfusion (IUT) throughout their entire pregnancy. During the treatment period of approximately 20 weeks, nipocalimab demonstrated a safety profile that supports further development of the treatment in HDFN.
Nipocalimab was granted Fast Track designation in July 2019 and orphan drug status in June 2020 by the U.S. Food and Drug Administration (FDA), and orphan medicinal product designation by the European Medicines Agency in October 2019 for HDFN.
“These early results represent an important step towards delivering a potential medication for expectant mothers at high risk of severe HDFN, and we are encouraged by what this treatment could mean for families affected by this potentially devastating disease. I would like to thank our patients and investigators for their participation and commitment in completing UNITY,” said Katie Abouzahr, M.D., Vice President, Autoantibody Portfolio Development Leader, Janssen Research & Development, LLC. “We look forward to sharing the full Phase 2 results of the UNITY trial at an upcoming scientific medical meeting while we continue to plan for a pivotal Phase 3 trial.”
About UNITY
UNITY is a global, multicenter, open-label, non-blinded Phase 2 clinical trial to evaluate the safety and efficacy of nipocalimab for the treatment of pregnant adults at high risk for severe HDFN.2 In the trial, 14 participants received once weekly intravenous infusions. The primary endpoint was live birth at or after GA of 32 weeks, without a need for an intrauterine transfusion (IUT) throughout the entire pregnancy. Adverse events were monitored up to approximately 24 weeks post-delivery for parents and up to approximately 96 weeks post-birth for children.2
About HDFN
HDFN is a rare autoantibody-driven disease where antibodies produced in a pregnant person’s immune system cross the placenta and attack fetal red blood cells — causing fetal hemolysis leading to anemia.1 The severe form of HDFN, which is categorized as an ultra-rare disease, can lead to life-threatening anemia.3Today, there are no approved therapeutics for the treatment of HDFN, and pregnancies affected by severe HDFN may necessitate repeated IUTs. IUTs are invasive, technically complex surgical procedures performed by specialists that may be associated with an increased rate of fetal mortality and premature birth.4 According to the American Journal of Obstetrics and Gynecology, in the U.S., it is estimated that up to 80 out of every 100,000 pregnancies are affected by HDFN each year.5
About Nipocalimab
Nipocalimab is an investigational, high affinity, fully human, aglycosylated, effectorless, monoclonal antibody that is believed to selectively block the Fc receptor (FcRn) to reduce levels of circulating immunoglobulin G (IgG) antibodies, including autoantibodies and alloantibodies that underlie multiple conditions. Nipocalimab is being studied in all three segments of autoantibody-driven disease: maternal fetal diseases mediated by maternal autoantibodies – also known as alloantibodies (e.g., HDFN); rare autoantibody diseases (e.g., generalized myasthenia gravis in adults and children, chronic inflammatory demyelinating polyneuropathy, warm autoimmune hemolytic anemia, and idiopathic inflammatory myopathies); and prevalent rheumatologic diseases (e.g., rheumatoid arthritis, Sjögren's syndrome, and systemic lupus erythematosus).2,6-14 Blockade of FcRn by nipocalimab has the potential to reduce overall autoantibody levels while maintaining immune function. FcRn blockade is also believed to prevent placental transfer of maternal alloantibodies to the fetus.2,15 Currently, nipocalimab is the only therapy in clinical development for the treatment of alloimmunized pregnant adults at risk of severe HDFN.
About the Janssen Pharmaceutical Companies of Johnson & Johnson
At Janssen, we’re creating a future where disease is a thing of the past. We’re the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular, Metabolism & Retina; Immunology; Infectious Diseases & Vaccines; Neuroscience; Oncology; and Pulmonary Hypertension.
Learn more at www.janssen.com. Follow us at www.twitter.com/JanssenGlobal.
Janssen Research & Development, LLC is a part of the Janssen Pharmaceutical Companies of Johnson & Johnson.
Johnson & Johnson succeeds in mid-stage trial for fetal disorder candidate
Feb. 06, 2023 9:15 AM ET
By: Dulan Lokuwithana, SA News Editor1 Comment
The Janssen unit of Johnson & Johnson (NYSE:JNJ) announced Monday that its candidate for rare fetal disorder severe hemolytic disease of the fetus and newborn (HDFN) reached the main goal in a Phase 2 study.
Zuranolone (SAGE-217/BIIB125)
ACI-24.060 Anti-Amyloid Beta Vaccine
Zuranolone (SAGE-217/BIIB125)
February 6, 2023
Sage Therapeutics and Biogen Announce FDA Accepts Filing of New Drug Application and Grants Priority Review of Zuranolone in the Treatment of Major Depressive Disorder and Postpartum Depression
Zuranolone is being evaluated as a potential 14-day, rapid-acting, once-daily, oral medication to treat major depressive disorder (MDD) and postpartum depression (PPD)
Depression is a public health issue with significant unmet medical need
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Feb. 6, 2023-- Sage Therapeutics, Inc. (Nasdaq: SAGE) and Biogen Inc. (Nasdaq: BIIB) announced the U.S. Food and Drug Administration (FDA) has accepted the filing of a New Drug Application (NDA) for zuranolone in the treatment of major depressive disorder (MDD) and postpartum depression (PPD). Zuranolone is an investigational drug being evaluated as a 14-day, rapid-acting, once-daily, oral treatment in adults with MDD and PPD. The application has been granted priority review and the FDA has assigned a Prescription Drug User Fee Act (PDUFA) action date of August 5, 2023.
This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20230205005025/en/
“We see potential for zuranolone, if approved, to be a meaningful new option that can help address the serious unmet need faced by the diverse populations struggling with MDD and PPD,” said Priya Singhal, M.D., M.P.H., Executive Vice President, Head of Development and Interim Head of Research and Global Safety and Regulatory Sciences at Biogen. “The FDA filing acceptance and granting of priority review are important milestones in the mission Biogen and our collaboration partner Sage share to advance the understanding and treatment of depression.”
Depression is one of the leading contributors to disability worldwide.1 It is estimated that more than 21 million adults in the U.S. experienced at least one major depressive episode in 2020, with nearly 14 million people diagnosed with major depressive disorder,2 and an estimated 500,000 cases of PPD annually.3 Symptoms of MDD and PPD have been shown to have an impact on a person’s overall quality of life, functioning and well-being. In 2018, the incremental economic burden of MDD was an estimated $326 billion in the U.S. alone.4
The zuranolone NDA includes data from the LANDSCAPE and NEST clinical development programs as well as a Phase 2 study of zuranolone completed by Shionogi in Japan in adults with MDD. The LANDSCAPE program includes five studies of zuranolone in adults with MDD (MDD-201B, MOUNTAIN, SHORELINE, WATERFALL, and CORAL). The NEST program includes two studies of zuranolone in adult women with PPD (ROBIN and SKYLARK).
“We feel a tremendous responsibility to patients with MDD and PPD to deliver a potential new treatment option, which is so desperately needed. Most current approved therapies may take weeks or months to work. We are committed to advancing treatments that could help physicians and patients by addressing depression symptoms quickly,” said Laura Gault, M.D., Ph.D., Chief Medical Officer at Sage. “We believe zuranolone, if approved, could offer a new way for physicians to support patients.”
Zuranolone, a neuroactive steroid, has a novel mechanism of action as a positive allosteric modulator of GABA-A receptors. In people with depression, it is thought to work by rapidly rebalancing dysregulated neuronal networks to help reset brain function. Zuranolone targets brain networks responsible for functions such as mood, arousal, behavior, and cognition.
Priority Review is granted by the FDA to applications for medicines that, if approved, would provide significant improvements in the effectiveness or safety of the treatment, diagnosis, or prevention of serious conditions.
About Major Depressive Disorder (MDD)
Major depressive disorder (MDD) is a common but serious mood disorder in which people experience depressive symptoms that impair their social, occupational, educational, or other important functioning, such as a depressed mood or loss of interest or pleasure in daily activities, consistently for at least a two-week period. It is estimated that in 2020, more than 21 million adults in the U.S. experienced at least one major depressive episode in the past year with nearly 14 million people diagnosed with major depressive disorder.2 There were approximately 190 million cases of MDD worldwide in 2020.5
About Postpartum Depression (PPD)
Postpartum depression (PPD) is one of the most common medical complications during and after pregnancy.6 PPD can have a serious negative impact on a woman, including significant functional impairment, depressed mood and/or loss of interest in her newborn, and associated symptoms of depression such as loss of appetite, difficulty sleeping, motor challenges, lack of concentration, loss of energy and poor self-esteem. PPD is estimated to affect approximately one in eight women who have given birth in the U.S. or approximately 500,000 women annually.3
About ZURANOLONE
Zuranolone (SAGE-217/BIIB125) is a once-daily, 14-day, investigational drug in development for the treatment of major depressive disorder (MDD) and postpartum depression (PPD). Zuranolone is an oral neuroactive steroid (NAS) GABA-A receptor positive allosteric modulator (PAM). The GABA system is the major inhibitory signaling pathway of the brain and central nervous system and contributes to regulating brain function.
Zuranolone is being evaluated in the LANDSCAPE and NEST clinical development programs. The two development programs include multiple studies examining use of zuranolone in several thousand people with a variety of dosing, clinical endpoints, and treatment paradigms. The LANDSCAPE program includes five studies of zuranolone in people with MDD (MDD-201B, MOUNTAIN, SHORELINE, WATERFALL, and CORAL Studies). The NEST program includes two placebo-controlled studies of zuranolone in women with PPD (ROBIN and SKYLARK Studies). Additionally, Shionogi completed a Phase 2 study of zuranolone in Japan in people with MDD.
About Sage Therapeutics
Sage Therapeutics is a biopharmaceutical company fearlessly leading the way to create a world with better brain health. Our mission is to pioneer solutions to deliver life-changing brain health medicines, so every person can thrive. For more information, please visit www.sagerx.com.
About Biogen
As pioneers in neuroscience, Biogen discovers, develops, and delivers worldwide innovative therapies for people living with serious neurological diseases as well as related therapeutic adjacencies. One of the world’s first global biotechnology companies, Biogen was founded in 1978 by Charles Weissmann, Heinz Schaller, Sir Kenneth Murray, and Nobel Prize winners Walter Gilbert and Phillip Sharp. Today, Biogen has a leading portfolio of medicines to treat multiple sclerosis, has introduced the first approved treatment for spinal muscular atrophy, and developed the first approved treatment to address a defining pathology of Alzheimer’s disease. Biogen is also commercializing biosimilars and focusing on advancing one of the industry’s most diversified pipelines in neuroscience that will transform the standard of care for patients in several areas of high unmet need.
We routinely post information that may be important to investors on our website at www.biogen.com. Follow us on social media - Twitter, LinkedIn, Facebook, YouTube.
View source version on businesswire.com: https://www.businesswire.com/news/home/20230205005025/en/
Source: Sage Therapeutics, Inc.
Biogen, Sage win FDA priority review for depression therapy
Feb. 06, 2023 7:25 AM ET
Biogen Inc. (BIIB), SAGESGIOF, SGIOY
By: Dulan Lokuwithana, SA News Editor
- Biogen (NASDAQ:BIIB) and Sage Therapeutics (NASDAQ:SAGE) announced Monday that the FDA accepted their New Drug Application (NDA) for oral depression therapy zuranolone under the agency’s priority review. Sage (SAGE) shares have added ~5%, while Biogen (BIIB) is trading flat in reaction.
- The FDA has granted August 05, 2023, as the action date for the NDA, which is intended for the U.S. approval of zuranolone for major depressive disorder (MDD) and postpartum depression (PPD).
- https://seekingalpha.com/news/3932229-biogen-sage-win-fda-priority-review-for-depression-therapy
- Biogen Inc. (BIIB), SAGE
- https://www.biogen.com/
- https://www.sagerx.com/home
aypirca™ (pirtobrutinib)
ACI-24.060 Anti-Amyloid Beta Vaccine
ACI-24.060 Anti-Amyloid Beta Vaccine
U.S. FDA Approves Jaypirca™ (pirtobrutinib), the First and Only Non-Covalent (Reversible) BTK Inhibitor, for Adult Patients with Relapsed or Refractory Mantle Cell Lymphoma After at Least Two Lines of Systemic Therapy, Including a BTK Inhibitor
January 27, 2023
Jaypirca is the first BTK inhibitor of any kind specifically approved for patients with mantle cell lymphoma previously treated with a covalent BTK inhibitor
In the BRUIN Phase 1/2 trial, covalent BTK inhibitor pre-treated patients with relapsed or refractory MCL achieved an overall response rate of 50%, with 13% of patients achieving a complete response
INDIANAPOLIS, Jan. 27, 2023 /PRNewswire/ -- Loxo@Lilly, the oncology unit of Eli Lilly and Company (NYSE: LLY), today announced that the U.S. Food and Drug Administration (FDA) approved Jaypirca™ (pirtobrutinib, 100 mg & 50 mg tablets) for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a Bruton's tyrosine kinase (BTK) inhibitor. Jaypirca was approved under the FDA's Accelerated Approval pathway based on response rate from the open-label, single-arm, international, Phase 1/2 study, called the BRUIN trial.1 Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Jaypirca, a highly selective kinase inhibitor, utilizes a novel binding mechanism and is the first and only FDA approved non-covalent (reversible) BTK inhibitor. Jaypirca can reestablish BTK inhibition in MCL patients previously treated with a covalent BTK inhibitor (ibrutinib, acalabrutinib, or zanubrutinib) and extend the benefit of targeting the BTK pathway.
"The approval of Jaypirca represents an important advance for patients with relapsed or refractory MCL, who currently have limited options and historically have had a poor prognosis following discontinuation of treatment with a covalent BTK inhibitor," said Michael Wang, M.D., Puddin Clarke Endowed Professor of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center. "These data indicate that Jaypirca can provide efficacy in patients previously treated with a covalent BTK inhibitor, potentially extending the time patients may benefit from BTK inhibition therapy. Jaypirca offers a new approach to targeting the BTK pathway following treatment with a covalent BTK inhibitor and has the potential to meaningfully impact the treatment paradigm for relapsed and refractory MCL patients."
The labeling for Jaypirca contains warnings and precautions for infections, hemorrhage, cytopenias, atrial fibrillation and flutter, second primary malignancies, and embryo-fetal toxicity. See Important Safety Information below and full Prescribing Information for additional information, including dosing modifications.
"We are pleased to bring a meaningful new therapeutic option to patients with MCL that can reestablish the benefit of targeting the BTK pathway after receiving multiple prior therapies, including a covalent BTK inhibitor," said Jacob Van Naarden, chief executive officer, Loxo@Lilly. "We are grateful to the patients, investigators, and other members of the clinical care teams for their contributions. Our team has been committed to rapidly advancing the development of Jaypirca for patients with MCL, and we look forward to building on this milestone by continuing to bring forward important new treatments for people with hematologic malignancies."
The FDA approval is based on data from a subset of patients in the BRUIN Phase 1/2 trial. The assessment of efficacy was based on 120 patients with MCL treated with Jaypirca 200 mg once daily until disease progression or unacceptable toxicity. Patients with active central nervous system lymphoma or allogeneic hematopoietic stem cell transplantation or CAR T-cell therapy within 60 days were excluded. Patients had received a median of three prior lines of therapy (range: 1 to 9), with 93% having two or more prior lines; all patients received one or more prior lines of therapy containing a covalent BTK inhibitor. Eighty-three percent (83%) of patients discontinued their last BTK inhibitor due to refractory or progressive disease. Efficacy was based on overall response rate (ORR) and duration of response (DOR) as assessed by an independent review committee (IRC) using 2014 Lugano criteria.
Jaypirca is expected to be available in the United States in the coming weeks.
The confirmatory Phase 3 trial (NCT04662255; BRUIN MCL-321) is currently enrolling patients.
See Important Safety Information below and full Prescribing Information for additional information.
Click here to view the mantle cell lymphoma infographic.
Click to view the Jaypirca product photos: 100 mg and 50 mg.
Click here to view the Jaypirca logo.
About the BRUIN Phase 1/2 Trial
The BRUIN Phase 1/2 clinical trial is the ongoing first-in-human, global, multi-center evaluation of Jaypirca in patients with hematologic malignancies, including mantle cell lymphoma (MCL).
The trial includes a Phase 1 dose-escalation phase, a Phase 1b combination arm, and a Phase 2 dose-expansion phase. The primary endpoint of the Phase 1 study is maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D). Secondary endpoints include safety, pharmacokinetics (PK), and preliminary efficacy measured by overall response rate (ORR) for monotherapy. The primary endpoint of the Phase 1b study is safety of the drug combinations. The secondary endpoints are PK and preliminary efficacy measured by ORR for the drug combinations. The primary endpoint for the Phase 2 study is ORR as determined by an independent review committee (IRC). Secondary endpoints include ORR as determined by investigator, best overall response (BOR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety, and PK.
About Jaypirca™ (pirtobrutinib)
Jaypirca (pirtobrutinib, formerly known as LOXO-305) (pronounced jay-pihr-kaa) is a highly selective (300 times more selective for BTK versus 98% of other kinases tested in preclinical studies), non-covalent (reversible) inhibitor of the enzyme BTK.2 BTK is a validated molecular target found across numerous B-cell leukemias and lymphomas including mantle cell lymphoma.3,4 Jaypirca is a U.S. FDA-approved oral prescription medicine, 100 mg or 50 mg tablets taken as a once-daily 200 mg dose with or without food until disease progression or unacceptable toxicity.
About Mantle Cell Lymphoma
MCL is a rare blood cancer and a form of non-Hodgkin lymphoma (NHL). Annually, about one in 200,000 people worldwide develop MCL.5
MCL arises in B lymphocytes, a type of white blood cell and part of the immune system. MCL frequently begins in B cells located in the mantle zone of the outer edge of lymph nodes. As the cancer progresses, it can spread to bone marrow, the spleen, the liver, or the digestive tract.5
INDICATIONS FOR JAYPIRCA
Jaypirca is a kinase inhibitor indicated for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Please see Prescribing Information and Patient Information for Jaypirca.
About Lilly
Lilly unites caring with discovery to create medicines that make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help more than 47 million people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges, redefining diabetes care, treating obesity and curtailing its most devastating long-term effects, advancing the fight against Alzheimer's disease, providing solutions to some of the most debilitating immune system disorders, and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/newsroom or follow us on Facebook, Instagram and LinkedIn. P-LLY
Jaypirca™ is a trademark owned by or licensed to Eli Lilly and Company, its subsidiaries, or affiliates.
View original content to download multimedia:https://www.prnewswire.com/news-releases/us-fda-approves-jaypirca-pirtobrutinib-the-first-and-only-non-covalent-reversible-btk-inhibitor-for-adult-patients-with-relapsed-or-refractory-mantle-cell-lymphoma-after-at-least-two-lines-of-systemic-therapy-including-a-301732669.html
SOURCE Eli Lilly and Company
Eli Lilly wins FDA accelerated approval for lymphoma therapy
Jan. 27, 2023 2:42 PM ET
By: Dulan Lokuwithana, SA News Editor1 Comment
The oncology division of Eli Lilly (NYSE:LLY) announced Friday that the FDA greenlighted its Bruton's tyrosine kinase (BTK) inhibitor Jaypirca as a late-line option for certain patients with mantle cell lymphoma (MCL), a rare blood cancer.
https://seekingalpha.com/news/3929112-lly-stock-wins-fda-accelerated-approval-lymphoma-therapy
ACI-24.060 Anti-Amyloid Beta Vaccine
ACI-24.060 Anti-Amyloid Beta Vaccine
ACI-24.060 Anti-Amyloid Beta Vaccine
AC Immune’s ACI-24.060 Anti-Amyloid Beta Vaccine For Alzheimer’s Shows Positive Initial Interim Safety And Immunogenicity In Phase 1b/2 ABATE Trial
Jan 26, 2023
AC Immune’s ACI-24.060 Anti-Amyloid Beta Vaccine for Alzheimer’s Shows Positive Initial Interim Safety and Immunogenicity in Phase 1b/2 ABATE Trial
- ACI-24.060 elicited an anti-Abeta antibody response in ABATE’s first, low dose cohort
- ACI-24.060 was generally well tolerated with no safety concerns observed
- With these findings, dosing in the second, higher dose Alzheimer’s cohort has begun
- Screening of cohort of study participants with Down syndrome also cleared to begin
- Further safety and immunogenicity findings from ABATE cohorts expected in H2 2023
- Initial data on amyloid plaque reduction measured via PET imaging anticipated in 2024
Lausanne, Switzerland, January 26, 2023 – AC Immune SA (NASDAQ: ACIU), a clinical-stage biopharmaceutical company pioneering precision medicine for neurodegenerative diseases, today announced the first interim safety, tolerability and immunogenicity findings from the Phase 1b/2 ABATE trial of its anti-amyloid-beta (Abeta) vaccine ACI-24.060 in patients with prodromal Alzheimer’s disease (AD). ABATE will now be expanded, as planned, to include individuals with Down syndrome (DS) and to evaluate higher doses in Alzheimer’s patients.
Targeting Abeta using antibodies has recently been validated with FDA approvals of new monoclonal antibody treatments for patients with AD. By eliciting polyclonal anti-Abeta antibodies, the ACI-24.060 anti-Abeta vaccine development program aims to ultimately deliver significant benefits to patients, their caregivers, and healthcare systems in terms of potential safety and tolerability, low frequency dosing, low overall costs and durable responses.
Early results from the first cohort of AD patients in ABATE showed that low dose ACI-24.060 could elicit an anti-Abeta antibody response as soon as week 6 (2 weeks after the second injection). The data show that ACI-24.060 vaccination has been safe and well tolerated to date. As a result, dosing in ABATE’s second, higher dose AD cohort has now begun and the trial is cleared to begin screening individuals with DS for part 2 of the study.
Dr. Andrea Pfeifer, CEO of AC Immune SA, commented: “We are delighted with the encouraging initial safety and immunogenicity findings for ACI-24.060 in ABATE reported today. We believe ACI-24.060’s successful development could provide patients with a novel therapeutic option offering numerous potential advantages in treatment, maintenance, and prevention settings. These early findings from ABATE represent an important step towards this goal, and we look forward to reporting more detailed data at a future conference.”
Dr. Johannes Streffer, CMO of AC Immune SA, commented: “ABATE’s innovative design includes interim Abeta PET imaging analyses that can be benchmarked against the levels of plaque clearance achieved with clinically-validated monoclonal antibodies. This will provide an opportunity for early de-risking of ACI-24.060 and potentially a rapid transition to a pivotal program. Moreover, the inclusion of cohorts of participants with DS in the trial positions us to potentially address the needs of a vastly underserved vulnerable population, virtually all of whom will develop amyloid plaques and AD. While looking forward to the trial’s continued advancement and upcoming data readouts, I want to thank the participants and investigators for their participation and support.”
About the Phase 1b/2 ABATE Study (ClinicalTrials.gov Identifier: NCT05462106)
The ABATE study is a Phase 1b/2, multicenter, adaptive, double-blind, randomized, placebo-controlled study to assess the safety, tolerability, immunogenicity, and pharmacodynamic effects of ACI-24.060 in subjects with prodromal Alzheimer’s disease and in adults with Down syndrome. All participants in the trial must have brain Abeta pathology confirmed by a positron emission tomography (PET) scan. The trial begins with a dose escalation phase in AD patients, during which various doses/dosing regimens may be evaluated, and also includes individuals with DS.
About ACI-24.060
ACI-24.060, derived from AC Immune’s SupraAntigen® platform, has been shown in preclinical studies to induce a strong polyclonal antibody response that matures and is maintained against both oligomeric and pyroglutamate-Abeta species, key pathological forms of Abeta believed to drive Abeta plaque formation and disease progression. ACI-24.060 is designed to enhance the formation of broad-spectrum protective antibodies with the same safety and tolerability previously demonstrated in the ACI-24 program in Phase 1 and 2 trials. This investigational candidate has the potential to efficiently inhibit plaque formation and increase plaque clearance, and thereby may reduce or prevent disease progression.
About AC Immune SA
AC Immune SA is a clinical-stage biopharmaceutical company that aims to become a global leader in precision medicine for neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and NeuroOrphan indications driven by misfolded proteins. The Company’s two clinically validated technology platforms, SupraAntigen® and Morphomer®, fuel its broad and diversified pipeline of first- and best-in-class assets, which currently features ten therapeutic and three diagnostic candidates, five of which are currently in Phase 2 clinical trials and one of which is in Phase 3. AC Immune has a strong track record of securing strategic partnerships with leading global pharmaceutical companies including Genentech, a member of the Roche Group, Eli Lilly and Company, and others, resulting in substantial non-dilutive funding to advance its proprietary programs and >$3 billion in potential milestone payments.
SupraAntigen® is a registered trademark of AC Immune SA in the following territories: AU, EU, CH, GB, JP, RU, SG and USA. Morphomer® is a registered trademark of AC Immune SA in CN, CH, GB, JP, KR, NO and RU.
The information on our website and any other websites referenced herein is expressly not incorporated by reference into, and does not constitute a part of, this press release.
Source: AC Immune SA
AC Immune rises ~10% as Alzheimer’s vaccine shows promise in early-stage trial
Jan. 26, 2023 7:51 AM ET
By: Ravikash, SA News Editor
- AC Immune (NASDAQ:ACIU) said its ACI-24.060 anti-amyloid beta (Abeta) vaccine for Alzheimer's disease (AD) showed positive initial interim safety and immunogenicity in a phase 1b/2 trial called ABATE.
- https://seekingalpha.com/news/3928320-ac-immune-rises-10-as-alzheimers-vaccine-shows-promise-in-early-stage-trial
- AC Immune SA (ACIU)
- https://www.acimmune.com/pipeline/
Breyanzi® (lisocabtagene maraleucel)
BXCL701 in combination with KEYTRUDA® (pembrolizumab)
Breyanzi® (lisocabtagene maraleucel)
Bristol Myers Squibb Announces TRANSCEND CLL 004 Trial of Breyanzi® (lisocabtagene maraleucel) Met Primary Endpoint of Complete Response Rate in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia
01/26/2023
CATEGORY:
PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) today announced topline results from TRANSCEND CLL 004, a Phase 1/2, open-label, single-arm, multicenter study evaluating Breyanzi (lisocabtagene maraleucel) in adults with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Results from TRANSCEND CLL 004 showed the study met the primary endpoint of complete response rate compared to historical controlin the prespecified subset of patients with R/R CLL that was refractory to a BTK inhibitor and pretreated with a BCL-2 inhibitor. No new safety signals were reported for Breyanzi in this study.
“CLL is an incurable disease with complex biology and immune dysregulation that has made the development of T cell-based therapies that provide deep remission very challenging,” said Anne Kerber, senior vice president, head of Cell Therapy Development, Bristol Myers Squibb. “In a population that has limited options, the TRANSCEND CLL 004 study represents the first multicenter trial evaluating a CAR T cell therapy in heavily pre-treated patients with relapsed or refractory CLL or SLL, with results showing the potential of Breyanzi as a personalized one-time treatment approach for patients with this difficult-to-treat disease.”
Bristol Myers Squibb will complete a full evaluation of the TRANSCEND CLL 004 data and work with investigators to present detailed results at an upcoming medical meeting, as well as discuss these results with health authorities. Bristol Myers Squibb thanks the patients and investigators who are participating in the TRANSCEND CLL 004 clinical trial.
About TRANSCEND CLL 004
TRANSCEND CLL 004 (NCT03331198) is a Phase 1/2 open-label, single-arm, multicenter study evaluating Breyanzi in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma. The Phase 1 dose escalation portion of the study assessed the safety and recommended dose for the subsequent Phase 2 expansion cohort. The Phase 2 portion of the study is evaluating Breyanzi at the recommended dose from the Phase 1 monotherapy arm. The primary endpoint of the Phase 2 portion of the study was complete response rate, including complete remission with incomplete bone marrow recovery, based on independent review committee according to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 guidelines.
About CLL and SLL
Chronic lymphocytic leukemia (CLL) is one of the most common types of leukemia in adults. In CLL, too many blood stem cells in the bone marrow become abnormal lymphocytes, and these abnormal cells have difficulty fighting infections. As the number of abnormal cells grows, there is less room for healthy white blood cells, red blood cells and platelets. Small lymphocytic lymphoma (SLL) also affects the lymphocytes, with cancer cells found mostly in the lymph nodes. While there are several treatments available for CLL and SLL, there is a need for additional effective therapies as there is no standard of care for relapsed or refractory CLL or SLL after prior therapy with targeted agents. Patients with relapsed or refractory disease have limited treatment options and generally experience shorter periods of response with each subsequent treatment.
About Breyanzi
Breyanzi is a CD19-directed CAR T cell therapy with a 4-1BB costimulatory domain, which enhances the expansion and persistence of the CAR T cells. Breyanzi is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal LBCL, and follicular lymphoma grade 3B who have refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy, or refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplant due to comorbidities or age, or relapsed or refractory disease after two or more lines of systemic therapy. Breyanzi is not indicated for the treatment of patients with primary central nervous system lymphoma. Please see the Important Safety Information section below, including Boxed WARNINGS for Breyanzi regarding cytokine release syndrome and neurotoxicity.
Breyanzi is also approved in Europe, Switzerland, Canada and Japan for relapsed and refractory LBCL after two or more lines of systemic therapy. Bristol Myers Squibb’s clinical development program for Breyanzi includes clinical studies in earlier lines of treatment for patients with relapsed or refractory LBCL and other types of lymphoma and leukemias. For more information, visit clinicaltrials.gov.
BREYANZI REMS
Because of the risk of CRS and neurologic toxicities, BREYANZI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS. The required components of the BREYANZI REMS are:
- Healthcare facilities that dispense and administer BREYANZI must be enrolled and comply with the REMS requirements.
- Certified healthcare facilities must have on-site, immediate access to tocilizumab.
- Ensure that a minimum of 2 doses of tocilizumab are available for each patient for infusion within 2 hours after BREYANZI infusion, if needed for treatment of CRS.
- Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense, or administer BREYANZI are trained on the management of CRS and neurologic toxicities.
Further information is available at www.BreyanziREMS.com, or contact Bristol Myers Squibb at 1-888-423-5436.
Please see full Prescribing Information, including Boxed WARNINGS and Medication Guide.
Bristol Myers Squibb: Creating a Better Future for People with Cancer
Bristol Myers Squibb is inspired by a single vision—transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine, and through innovative digital platforms, are turning data into insights that sharpen their focus. Deep scientific expertise, cutting-edge capabilities and discovery platforms enable the company to look at cancer from every angle. Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. Because as a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.
Learn more about the science behind cell therapy and ongoing research at Bristol Myers Squibb here.
About Bristol Myers Squibb
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.
Source: Bristol Myers Squibb
Bristol Myers says trial for CAR T therapy met main goal in leukemia
Jan. 26, 2023 7:22 AM ET
Bristol-Myers Squibb Company (BMY)
By: Dulan Lokuwithana, SA News Editor
- Bristol Myers Squibb (NYSE:BMY) announced Thursday that a Phase 1/2 trial for its CAR T cell therapy Breyanzi reached the primary endpoint in adults with relapsed or refractory chronic lymphocytic leukemia (CLL).
- https://seekingalpha.com/news/3928300-bristol-myers-says-trial-car-t-therapy-met-main-goal-leukemia
- Bristol-Myers Squibb Company (BMY)
- https://www.breyanzi.com/
MRTX1133
BXCL701 in combination with KEYTRUDA® (pembrolizumab)
Breyanzi® (lisocabtagene maraleucel)
Mirati Announces IND Clearance by U.S. FDA Enabling Phase 1 Initiation for First-in-Class Oral KRASG12D Selective Inhibitor, MRTX1133
01/19/2023
IND demonstrates Mirati's leadership in KRAS, representing the Company's third KRAS or KRAS-signaling program to enter clinical development
SAN DIEGO, Jan. 19, 2023 /PRNewswire/ -- Mirati Therapeutics, Inc. (NASDAQ: MRTX), announced today the U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application of MRTX1133, a potential first-in-class oral KRASG12D selective inhibitor for clinical evaluation. KRASG12D mutations impact approximately 180,000 patients in the US and Europe, representing approximately a 2.5-fold increase in prevalence compared to KRASG12C mutations. No targeted oncology treatment options currently exist for these patients.
MRTX1133 is a highly potent investigational inhibitor of the KRASG12D driver mutation and demonstrated selective and reversible inhibition of KRASG12D in both its active and inactive states. In addition, MRTX1133 administration resulted in marked tumor response in preclinical KRASG12D mutated pancreatic cancer models as well as lung and colorectal cancer models. MRTX1133 has demonstrated favorable properties including a low risk for off-target activity and drug interactions and a predicted human half-life of greater than 50 hours.
"The clearance by the FDA to initiate clinical evaluation of MRTX1133, the third program in our KRAS franchise to enter clinical development, is illustrative of the innovative approach to drug discovery and demonstrates the best-in-class capabilities of the Mirati team. This particular mutation has been difficult to target, and we are confident in our novel oral formulation strategy, which we believe will enable near-complete target inhibition over the full dosing interval," said James Christensen, Ph.D. chief scientific officer, Mirati Therapeutics, Inc. "We are thrilled to advance MRTX1133 into clinical development and the potential to positively impact people living with KRASG12D-mutated cancers."
The Phase 1/2 clinical trial will launch in early 2023 with plans for multiple expansion cohorts in pancreatic, colorectal, lung and other KRASG12D tumor types.
About Mirati Therapeutics, Inc.
Mirati Therapeutics, Inc. is a biotechnology company whose mission is to discover, design and deliver breakthrough therapies to transform the lives of patients with cancer and their loved ones. The company is relentlessly focused on bringing forward therapies that address areas of high unmet need, including lung cancer, and advancing a pipeline of novel therapeutics targeting the genetic and immunological drivers of cancer. Unified for patients, Mirati's vision is to unlock the science behind the promise of a life beyond cancer.
For more information about Mirati, visit us at Mirati.com or follow us on Twitter, LinkedIn and Facebook.
About MRTX1133
MRTX1133 is an investigational, highly potent, selective and reversible small molecule inhibitor of KRASG12D that is optimized to sustain near complete target inhibition with the potential to be both a first and best-in-class treatment option. MRTX1133 is entering Phase 1 clinical evaluation in 2023 investigating the drug's impact on KRASG12D-driven cancers. For more information visit Mirati.com/science.
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SOURCE Mirati Therapeutics, Inc.
FDA clears Mirati's investigational new drug application for its inhibitor MRTX1133
Jan. 19, 2023 5:15 PM ET
Mirati Therapeutics, Inc. (MRTX)
By: Anuron Mitra, SA News Editor
- Mirati Therapeutics (NASDAQ:MRTX) on Thursday said the U.S. Food and Drug Administration had cleared its investigational new drug (IND) application for its inhibitor MRTX1133.
- https://seekingalpha.com/news/3926159-fda-clears-miratis-investigational-new-drug-application-for-its-inhibitor-mrtx1133
- Mirati Therapeutics, Inc. (MRTX)
- https://www.mirati.com/science/programs/kras-inhibitors/kras-g12d-inhibitor/
- https://www.mirati.com/
BXCL701 in combination with KEYTRUDA® (pembrolizumab)
BXCL701 in combination with KEYTRUDA® (pembrolizumab)
BXCL701 in combination with KEYTRUDA® (pembrolizumab)
BioXcel Therapeutics Announces Promising Top-Line Results from Phase 2 Trial of BXCL701 in Aggressive Form of Rare Prostate Cancer
Jan 11, 2023
Results demonstrate encouraging response rate of BXCL701 plus KEYTRUDA® (pembrolizumab) in patients with SCNC
Full data will be presented at the 2023 ASCO Genitourinary Cancers Symposium in February
NEW HAVEN, Conn., Jan. 11, 2023 (GLOBE NEWSWIRE) --
BioXcel Therapeutics, Inc. (Nasdaq: BTAI), a biopharmaceutical company utilizing artificial intelligence approaches to develop transformative medicines in neuroscience and immuno-oncology, today announced promising top-line data from its Phase 2 trial of BXCL701, the Company's investigational, oral innate immune activator, in combination with KEYTRUDA® (pembrolizumab) in small cell neuroendocrine metastatic castration-resistant prostate cancer (SCNC) patients. Full data have been submitted to the 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU).
“We are pleased that BXCL701 in combination with pembrolizumab has demonstrated an encouraging response rate in this difficult-to-treat cancer with no currently approved FDA therapies,” said Vincent J. O’Neill, M.D., Chief R&D Officer, OnkosXcel Therapeutics, a wholly owned subsidiary of BioXcel Therapeutics. “BXCL701’s promising profile as an oral innate immune activator with a large safety dataset and novel mechanism of action further supports OnkosXcel’s pipeline and use of BioXcel’s AI platform, and reinforces our confidence in BXCL701’s potential to enable checkpoint inhibitor therapy in traditionally cold cancers.”
SCNC represents a rare, underserved, growing patient population, with SCNC cases increasing due to earlier and more widespread use of androgen receptor inhibitors. In 2022, there were an estimated 268,5001 new prostate cancer patients, with approximately 10,740 patients progressing to SCNC.
The Phase 2a trial is an open-label, multicenter study to evaluate the safety and efficacy of BXCL701 in combination with pembrolizumab in men with SCNC. Eligibility criteria include histologically confirmed de novo or treatment-emergent SCNC, progression as defined by PCWG3 criteria, and at least 1 prior line of chemotherapy for locally advanced or metastatic prostate cancer. 28 evaluable SCNC patients received 0.3 mg of BXCL701 twice daily (BID) on days 1 through 14 of a 21-day cycle (0.2 mg BID the first week of Cycle 1) plus 200 mg of pembrolizumab administered intravenously on day 1 and every subsequent 21 days. The primary endpoint of the trial is a composite response rate defined as RECIST 1.1 and/or PSA50 and/or CTC count conversion. Secondary endpoints include duration of response, progression-free survival, overall survival, and biomarker evaluation as measured by changes in circulating cytokines and correlation of outcome with baseline tumor characteristics.
About BXCL701
BXCL701 is an investigational, oral innate immune activator designed to initiate inflammation in the tumor microenvironment. Approved and experimental immunotherapies often struggle to address cancers that appear “cold” or uninflamed. Therefore, BXCL701 may render “cold” tumors “hot,” making them more detectable by the adaptive immune system and thereby facilitating the development of a strong anti-cancer immune response. BioXcel Therapeutics’ preclinical data supports BXCL701’s synergy with both current checkpoint inhibitor-based therapies and emerging immunotherapies directed to activate T-cells. BXCL701 is currently being developed as a potential therapy for the treatment of aggressive forms of prostate cancer and advanced solid tumors that are refractory or treatment naïve to checkpoint inhibitors. BXCL701 has received Orphan Drug Designation from the U.S. Food & Drug Administration in four indications: acute myelogenous leukemia, pancreatic cancer, stage IIb to IV melanoma, and soft tissue sarcoma.
About OnkosXcel Therapeutics, LLC
OnkosXcel Therapeutics, LLC is a wholly owned subsidiary of BioXcel Therapeutics, Inc., focused on developing transformative medicines in oncology utilizing artificial intelligence approaches. The subsidiary was formed in 2022 to develop BXCL701, a Phase 2, investigational, oral innate immune activator for the treatment of aggressive forms of prostate cancer and advanced solid tumors that are refractory or treatment naïve to checkpoint inhibitors, as well as other immuno-oncology focused assets.
About BioXcel Therapeutics, Inc.
BioXcel Therapeutics, Inc., is a biopharmaceutical company utilizing artificial intelligence approaches to develop transformative medicines in neuroscience and immuno-oncology. The Company’s drug re-innovation approach leverages existing approved drugs and/or clinically validated product candidates together with big data and proprietary machine learning algorithms to identify new therapeutic indications. The Company’s commercial product, IGALMI™ (developed as BXCL501), is a proprietary, sublingual film formulation of dexmedetomidine approved for the acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults. The safety and effectiveness of IGALMI have not been established beyond 24 hours from the first dose. For more information, please visit IGALMIhcp.com and also see the IGALMI full Prescribing Information. BXCL501 is under evaluation for at-home use for the acute treatment of agitation in bipolar and schizophrenia patients, for acute treatment of Alzheimer’s-related agitation, and as an adjunctive treatment for major depressive disorder. The safety and efficacy of BXCL501 for these uses have not been established. The Company is also developing BXCL502 as a potential therapy for chronic agitation in dementia. Under its subsidiary, OnkosXcel Therapeutics LLC, the Company is developing BXCL701, an investigational, oral innate immune activator for the treatment of aggressive forms of prostate cancer and advanced solid tumors that are refractory or treatment naïve to checkpoint inhibitors. The safety and efficacy of BXCL502 and BXCL701 have not been established. For more information, please visit bioxceltherapeutics.com.
Source: BioXcel Therapeutics, Inc.
BioXcel's BXCL701, Keytruda combo shows promise in mid-stage trial for prostate cancer
Jan. 11, 2023 7:33 AM ET
BioXcel Therapeutics, Inc. (BTAI), MRK
By: Ravikash, SA News Editor
- BioXcel Therapeutics (NASDAQ:BTAI) said its oral medicine BXCL701 in combination with Merck's (NYSE:MRK) Keytruda showed encouraging response rate in patients with a type of prostate cancer in a phase 2a trial.
- The study evaluated BXCL701 in combination with Keytruda (pembrolizumab) in men with small cell neuroendocrine metastatic castration-resistant prostate cancer (SCNC).
- In the trial, 28 evaluable patients received the drug combination. The main goal of the study is a composite response rate, while secondary goals include duration of response, progression-free survival, overall survival, and biomarker evaluation.
- https://seekingalpha.com/news/3923614-bioxcels-bxcl701-keytruda-combo-shows-promise-in-mid-stage-trial-for-prostate-cancer
- BioXcel Therapeutics, Inc. (BTAI), MRK
- https://www.bioxceltherapeutics.com/our-pipeline/
LP-284
IBI351 (KRASG12C Inhibitor)
BXCL701 in combination with KEYTRUDA® (pembrolizumab)
FDA Grants Lantern Pharma Orphan Drug Designation for Drug Candidate LP-284 in Mantle Cell Lymphoma
January 05, 2023 8:59am EST
- The Orphan Drug Designation strengthens LP-284’s clinical development path and provides the opportunity for additional market exclusivity and commercial protection.
- Lantern is anticipating filing the IND with the FDA and initiating a first-in-human Phase 1 trial for LP-284 in B-cell non-Hodgkin’s lymphomas (NHL), including mantle cell lymphoma (MCL), by mid 2023.
- In the US, MCL is diagnosed in approximately 4,500 patients each year and has an estimated annual market potential of $600 million.
DALLAS--(BUSINESS WIRE)-- Lantern Pharma Inc. (NASDAQ: LTRN), a clinical stage biopharmaceutical company using its proprietary RADR® artificial intelligence ("A.I.") and machine learning (“M.L.”) platform to transform the cost, pace, and timeline of oncology drug discovery and development, today announced that the U.S. Food and Drug Administration (FDA) has granted LP-284 Orphan Drug Designation (ODD) for the treatment of mantle cell lymphoma (MCL). MCL is a rare and aggressive form of B-cell non-Hodgkin's lymphoma (NHL) that is typically diagnosed at advanced stages in elderly patients. As nearly all MCL patients acquire resistance and relapse from treatment with standard-of-care (SOC) agents, there is an urgent and unmet clinical need for new and effective therapies to treat MCL.
LP-284 is a novel small molecule agent that preferentially damages DNA in cancer cells harboring mutations in DNA damage repair pathways. Lantern is developing LP-284 for several aggressive B-cell NHL’s, including MCL and double hit lymphoma (DHL), where LP-284 has shown potent anti-tumor activity in preclinical models. Lantern has been able to advance LP-284 from initial RADR® A.I. insights regarding anti-cancer activity and potential mechanisms of action in hematological cancers, to selection of specific subtypes of lymphomas with superior response, to late stage IND enabling studies and initial design of first in human clinical trials in less than 2 years.
"Receiving Orphan Drug Designation is an important milestone for our latest drug candidate, LP-284, and further validates our data-driven approach to oncology drug discovery and development” stated Panna Sharma, President & CEO of Lantern Pharma. "At ASH, we recently reported positive preclinical data demonstrating LP-284’s potent anti-tumor activity in new MCL tumors and also against tumors that had grown resistant to the MCL standard-of-care agents Ibrutinib and Bortezomib. These findings are critically pertinent due to the high relapse rate, and poor prognosis of the majority of MCL patients,” continued Sharma.
“This orphan designation is the fourth overall designation granted to Lantern, with the other three granted for our drug candidate LP-184. Acquiring these orphan designations is a key element of our business model as they provide a number of benefits including seven years of market exclusivity and eligibility for expedited drug development programs. Looking forward, these designations further position Lantern to advance our discussions with biopharma companies for partnering and collaborative development opportunities.”
The FDA's Office of Orphan Products Development grants orphan status to drugs intended for the safe and effective treatment, diagnosis or prevention of rare diseases or conditions affecting fewer than 200,000 people in the United States. ODD is designed to provide drug developers with various benefits to support the development of novel drugs, including market exclusivity for seven years upon FDA approval, eligibility for tax credits for qualified clinical trials, waiver of marketing registration application fees, reduced annual product fees, clinical protocol assistance and qualification for expedited development programs.
In addition to the ODD granted for LP-284 in MCL, Lantern was previously granted ODD’s by the FDA for its drug candidate LP-184 for the treatment of malignant gliomas, atypical teratoid rhabdoid tumors (ATRT), and pancreatic cancer. Lantern has also been granted a Rare Pediatric Disease Designation for LP-184 in ATRT.
About Lantern Pharma:
Lantern Pharma (NASDAQ: LTRN) is a clinical-stage oncology-focused biopharmaceutical company leveraging its proprietary RADR® A.I. and machine learning platform to discover biomarker signatures that identify patients most likely to respond to