FDA Approves Miebo (perfluorohexyloctane) Ophthalmic Solution for the Treatment of the Signs and Symptoms of Dry Eye Disease

Bausch + Lomb Corporation, announced that the U.S. Food and Drug Administration (FDA) has approved Miebo™ (perfluorohexyloctane ophthalmic solution; formerly known as NOV03), for the treatment of the signs and symptoms of dry eye disease (DED). Miebo is the first and only FDA-approved treatment for DED that directly targets tear evaporation.

“Today’s FDA approval of Miebo further advances DED treatment by addressing a significant unmet need for millions of people suffering with this disease,” said Brent Saunders, chairman and CEO, Bausch + Lomb. “We are proud to bring to market the first and only prescription eye drop approved in the United States for the treatment of DED that directly targets evaporation. We expect to make Miebo commercially available in the second half of this year.”

DED affects millions of Americans and is one of the most common ocular surface disorders.1 A leading cause of DED is excessive tear evaporation, which due to an altered tear lipid layer, is often associated with the clinical signs of Meibomian gland dysfunction (MGD). An unstable tear film triggers increased ocular surface desiccation, inflammation and damage to the ocular surface.2,3 Miebo is designed to reduce tear evaporation at the ocular surface.4,5

In GOBI and MOJAVE, two phase 3 pivotal clinical trials which enrolled more than 1,200 patients (randomized 1:1 to Miebo or hypotonic saline) with a history of DED and clinical signs of MGD, Miebo consistently met its primary clinical sign and patient-reported symptom endpoint.

"In the two pivotal clinical trials, Miebo addressed the persistent and chronic nature of DED by providing sustained improvement in both the signs and symptoms of DED,” said Preeya Gupta, M.D., cornea and cataract surgeon, Triangle Eye Consultants, Raleigh, North Carolina. “Because Miebo inhibits evaporation, it may be an appropriate treatment option for patients whose tear evaporation exceeds tear supply.”

“Tear evaporation, which is a leading driver of DED, presents a significant treatment challenge. With the approval of Miebo, eye care professionals can now take a new approach to DED therapy with a first-in-class water- and preservative-free prescription treatment option that specifically addresses tear evaporation,” said Paul Karpecki, O.D., director, Cornea and External Disease, Kentucky Eye Institute, and associate professor, University of Pikeville, Kentucky College of Optometry.

Ref : Read More  

FDA Approves Lumryz (sodium oxybate) for Cataplexy or Excessive Daytime Sleepiness in Adults with Narcolepsy

In continuation of my update on Lumryz

Avadel Pharmaceuticals plc   a biopharmaceutical company announced   the U.S. Food & Drug Administration (FDA)  final approval to Lumryz, an extended-release formulation of sodium oxybate indicated to be taken once at bedtime for the treatment of cataplexy or excessive daytime sleepiness (EDS) in adults with narcolepsy. With final approval, Lumryz becomes the first and only FDA approved once-at-bedtime oxybate for people living with narcolepsy. Lumryz was additionally granted Orphan Drug Exclusivity by the FDA.

“Today’s landmark approval and receipt of Orphan Drug Exclusivity represents a major milestone for both Avadel and people living with narcolepsy. As we have heard from key stakeholders, previously approved narcolepsy therapies have the potential to disrupt sleep by either causing insomnia or through forced awakening during the middle of the night for their crucial second dose. Lumryz can now offer people with narcolepsy the opportunity for an uninterrupted night sleep while receiving the full benefit of their prescribed treatment in one single bedtime dose that addresses their symptoms of narcolepsy,” said Greg Divis, Chief Executive Officer of Avadel. “We would like to thank the patients, caregivers, clinical trial investigators, healthcare providers, and advocates who have tirelessly partnered with us throughout the drug development process and look forward to providing the narcolepsy community access to now approved Lumryz.”

Narcolepsy is a chronic neurological condition that impairs the brain's ability to regulate the sleep-wake cycle. The condition affects approximately one in 2,000 people in the United States with the cardinal symptom of EDS. Additional symptoms can vary by person but may include disrupted nighttime sleep, a sudden loss of muscle tone usually triggered by strong emotion (cataplexy), sleep paralysis and hallucinations.

“This long-awaited therapy for people living with narcolepsy fills a critical unmet need by avoiding the burden of a second middle-of-the-night dose that immediate-release oxybate products require. The once-at-bedtime dosing regimen of Lumryz may help restore a more natural sleep-wake cycle,” said Michael J. Thorpy, M.D., an investigator from the REST-ON Phase 3 trial and Director at the Sleep-Wake Disorders Center at Montefiore Medical Center and Professor of Neurology at the Albert Einstein College of Medicine.

The FDA’s final approval of Lumryz was based on positive results from the pivotal Phase 3 REST-ON clinical study completed in March 2020. In the REST-ON Phase 3 trial, once-at-bedtime Lumryz demonstrated highly statistically significant (p<0.001) and clinically meaningful improvement compared to placebo across all three co-primary endpoints (Maintenance of Wakefulness Test, Clinical Global Impression-Improvement and mean weekly cataplexy attacks) for all three doses evaluated, 6, 7.5 and 9 grams.

With this approval, the FDA has also found Lumryz to be clinically superior to currently marketed twice-nightly oxybate products and granted Lumryz seven years of Orphan Drug Exclusivity. In particular, FDA found that Lumryz makes a major contribution to patient care over currently available, twice-nightly oxybate products by providing a once-nightly dosing regimen that avoids nocturnal arousal to take a second dose. The FDA's Orphan Drug program is designed to support the development of drugs that treat a condition affecting less than 200,000 U.S. patients. The seven-year market exclusivity for Lumryz began on the date of FDA approval, May 1, 2023.

“For people living with narcolepsy, and for all of us who advocate for this community, the approval of Lumryz is an important step forward,” said Julie Flygare, JD, President and CEO of Project Sleep. “People living with narcolepsy will finally have a new treatment option to manage EDS and cataplexy, and the fact that this new oxybate option allows for reduced dosing frequency is a game-changing advancement that shows Avadel’s commitment to understanding the patient experience. We look forward to continued collaboration with Avadel as part of a shared mission to positively impact the lives of people with narcolepsy.”

Lumryz has a boxed warning as a central nervous system depressant, and for its potential for abuse and misuse. Lumryz is available only through a restricted program under a Risk Evaluation and Mitigation Strategy called the Lumryz REMS. Most common adverse reactions (incidence > 5% and greater than placebo) reported for all doses of Lumryz combined were nausea, dizziness, enuresis, headache, and vomiting.

https://en.wikipedia.org/wiki/Sodium_oxybate

FDA Approves Lumryz (sodium oxybate) for Cataplexy or Excessive Daytime Sleepiness in Adults with Narcolepsy

FDA Approves Mydcombi (tropicamide and phenylephrine hydrochloride) Ophthalmic Spray for Inducing Mydriasis

In continuation of my update on phenylephrine hydrochloride

Phenylephrine

Tropicamide

Eyenovia, Inc, announced  the U.S. Food and Drug Administration (FDA)  approval of Mydcombi (tropicamide and phenylephrine hydrochloride ophthalmic spray) 1%/2.5% for inducing mydriasis for diagnostic procedures and in conditions where short term pupil dilation is desired. This represents the first approved fixed dose combination of tropicamide and phenylephrine in the United States and also the first product using Eyenovia’s proprietary Optejet device to be approved by any regulatory authority.

Mydcombi is designed to improve the efficiency of the estimated 106 million office-based comprehensive eye exams performed every year in the United States, as well as the estimated 4 million pharmacologic mydriasis applications for cataract surgery. The product is contraindicated and should not be used in patients with known hypersensitivity to any component of the formulation.

“The approval of Mydcombi, our first FDA approved product, represents the culmination of years of tireless effort by the entire Eyenovia team, and I would like to express my sincere gratitude to the associates and technical experts who helped advance this important program through this transformational milestone,” stated Michael Rowe, chief executive officer of Eyenovia. “We look forward to introducing Mydcombi to key offices beginning this summer while we bring our internal manufacturing capabilities on-line for 2024.”

“Perhaps more importantly, FDA approval of Mydcombi provides critical validation of the Optejet as it is the first product approved using the Optejet platform, which is core not only to our internal development programs, including MicroLine for presbyopia, but our partnered programs as well. We see opportunities to unlock significant opportunities in the future treatment of other ophthalmic conditions including glaucoma and dry eye. I am confident in our ability to maintain our current momentum.”

“I am proud of our team for this significant achievement – which represents many ‘firsts’ for eye care,” stated Dr. Sean Ianchulev, Founder and Chairman of Eyenovia’s Board of Directors. “The use of eye dropper bottles has presented challenges for dosing in ophthalmologic settings in millions of patients. We can do better now using sophisticated micro-array print delivery with physiologic dosing that is similar to the natural tear film volume.”

https://en.wikipedia.org/wiki/Phenylephrine

https://en.wikipedia.org/wiki/Tropicamide

Read More 

FDA Grants Accelerated Approval for Qalsody (tofersen) for the Treatment of Amyotrophic Lateral Sclerosis Associated with a Mutation in the SOD1 Gene

Biogen Inc. (Nasdaq: BIIB) announced the U.S. Food and Drug Administration (FDA)   approval of  Qalsody (tofersen) 100 mg/15mL injection for the treatment of amyotrophic lateral sclerosis (ALS) in adults who have a mutation in the superoxide dismutase 1 (SOD1) gene. This indication is approved under accelerated approval based on reduction in plasma neurofilament light chain (NfL) observed in patients treated with Qalsody. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trial(s).1 The ongoing Phase 3 ATLAS study of tofersen in people with presymptomatic SOD1-ALS will serve as the confirmatory trial.

Neurofilaments are proteins that are released from neurons when they are damaged, making them a marker of neurodegeneration.6

“For more than a decade, Biogen has been steadfast in our commitment to pursuing treatments for ALS, and I want to thank the scientists as well as the entire ALS community who have all worked tirelessly to bring this first-of-its-kind treatment to people with SOD1-ALS,” said Christopher A. Viehbacher, President and Chief Executive Officer of Biogen. “Today also marks a pivotal moment in ALS research as we gained, for the first time, consensus that neurofilament can be used as a surrogate marker reasonably likely to predict clinical benefit in SOD1-ALS. We believe this important scientific advancement will further accelerate innovative drug development for ALS.”

Qalsody is the first approved treatment to target a genetic cause of ALS. Biogen collaborated with Ionis Pharmaceuticals on the early development of tofersen.

Warnings and precautions associated with Qalsody were serious neurologic events, including myelitis and/or radiculitis; papilledema and elevated intracranial pressure; and aseptic meningitis. If symptoms consistent with myelitis, radiculitis papilledema, elevated intracranial, or aseptic meningitis develop, diagnostic workup and treatment should be initiated according to the standard of care. Management may require interruption or discontinuation of Qalsody. The most common adverse reactions that occurred in ≥10% of Qalsody treated participants and more than the placebo arm were pain, fatigue, arthralgia, cerebrospinal (CSF) white blood cell increased, and myalgia.

“Since SOD1 mutations were first identified as a cause of ALS 30 years ago, the familial ALS community has been searching for genetically targeted treatments. Qalsody offers families who have lost generation after generation in the prime of their life to this devastating disease a therapy targeting the underlying cause of SOD1-ALS. Today marks an important moment in ALS research as Qalsody is the first ALS treatment approved based on a biomarker,” said Jean Swidler, chair of Genetic ALS & FTD: End the Legacy. “We are excited to see what future therapies are developed now that it is understood that lowering levels of neurofilament provides important evidence that a treatment is affecting the neurodegenerative process.”

The efficacy of Qalsody was assessed in a 28-week randomized, double-blind, placebo-controlled clinical study in patients 23 to 78 years of age with weakness attributable to ALS and a SOD1 mutation confirmed by a central laboratory. One hundred eight (108) patients were randomized 2:1 to receive treatment with either Qalsody 100 mg (n=72) or placebo (n=36) for 24 weeks (3 loading doses followed by 5 maintenance doses). Concomitant riluzole and/or edaravone use was permitted for patients and at baseline 62% of patients were taking riluzone, and 8% of patients were taking edaravone.

Over 28 weeks in VALOR, participants in the primary analysis population (n=60) treated with Qalsody experienced less decline from baseline as measured by the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) compared to placebo, though the results were not statistically significant (Qalsody-placebo adjusted mean difference [95% CI]: 1.2 [-3.2, 5.5]). In the overall intent-to-treat population (n=108), Qalsody-treated participants experienced a 55% reduction in plasma NfL compared to a 12% increase in placebo-treated participants (difference in geometric mean ratios for Qalsody to placebo: 60%; nominal p<0.0001). Additionally, levels of CSF SOD1 protein, an indirect measure of target engagement, were reduced by 35% in the Qalsody-treated group compared to 2% in the corresponding placebo group (difference in geometric mean ratios for Qalsody to placebo: 34%; nominal p<0.0001).

https://en.wikipedia.org/wiki/Tofersen

https://go.drugbank.com/drugs/DB14782

FDA Grants Accelerated Approval for Qalsody (tofersen) for the Treatment of Amyotrophic Lateral Sclerosis Associated with a Mutation in the SOD1 Gene

FDA Approves Abilify Asimtufii (aripiprazole) for the Treatment of Schizophrenia or Maintenance Monotherapy Treatment of Bipolar I Disorder in Adults

In continuation of my update on aripiprazole

Otsuka Pharmaceutical Co., Ltd. (Otsuka) and Lundbeck Pharmaceuticals LLC (Lundbeck) announced the U.S. Food and Drug Administration (FDA)   approval of  the New Drug Application (NDA) for Abilify Asimtufii® (aripiprazole) extended-release injectable suspension for intramuscular use, a once-every-two-months injection for the treatment of schizophrenia in adults or for maintenance monotherapy treatment of bipolar I disorder in adults.

Abilify Asimtufii offers two months of sustained therapeutic concentrations with one dose. Each dose is provided in a single-chamber, prefilled syringe, and is administered by a healthcare professional to appropriate patients via intramuscular injection in the gluteal muscle. Long-acting injectables provide continuous delivery of antipsychotic medication and can maintain therapeutic plasma concentrations, which may help to maintain symptom control of schizophrenia and bipolar I disorder.

"We are pleased to offer this new treatment option for people living with schizophrenia or bipolar I disorder that may delay the time to relapse," said John Kraus, M.D., Ph.D., executive vice president and chief medical officer at Otsuka Pharmaceutical Development & Commercialization, Inc. "This approval underscores Otsuka's commitment to innovate and continuously evolve to meet the needs of the communities we serve."

The efficacy of Abilify Asimtufii is based on the adequate and well-controlled studies of Abilify Maintena (aripiprazole) in the treatment of schizophrenia or maintenance treatment of bipolar I disorder in adults. The aripiprazole concentrations of Abilify Asimtufii were explored in a pharmacokinetic bridging study which was a 32-week, open-label, multiple-dose, randomized, parallel-arm, multicenter study (N=266) in patients living with schizophrenia and bipolar I disorder. The once-every-two-months, long-acting injectable formulation in 960 mg and 720 mg prefilled syringes delivers sustained plasma concentrations similar to that demonstrated in studies with aripiprazole monohydrate once-monthly, long-acting injectable, resulting in similar sustained efficacy.

"This approval is important news for patients, families, and healthcare providers. We hope that the use of Abilify Asimtufii in treatment plans will have a positive impact on those living with schizophrenia or bipolar I disorder," said Johan Luthman, executive vice president, R&D, Lundbeck. "We are grateful to the patients and researchers who made this major milestone possible."

https://en.wikipedia.org/wiki/Aripiprazole

FDA Approves Abilify Asimtufii (aripiprazole) for the Treatment of Schizophrenia or Maintenance Monotherapy Treatment of Bipolar I Disorder in Adults

FDA Approves Uzedy (risperidone) Extended-Release Injectable Suspension for the Treatment of Schizophrenia in Adults

In continuation of my update on Uzedy (risperidone)

Teva Pharmaceuticals,  announced  the U.S. Food and Drug Administration (FDA)  approval of  Uzedy (risperidone) extended-release injectable suspension for the treatment of schizophrenia in adults. Uzedy is the first subcutaneous, long-acting formulation of risperidone that utilizes SteadyTeq™, a copolymer technology proprietary to MedinCell that controls the steady release of risperidone. Therapeutic blood concentrations are reached within 6-24 hours of a single dose. 

“Uzedy embodies Teva’s commitment to bringing innovative advances to patients and to providing people living with schizophrenia an important new treatment option that was designed to address certain treatment challenges and may decrease the risk of relapse,” said Richard Francis, President and CEO of Teva. “The approval of Uzedy is a culmination of a multidisciplinary effort across Teva and MedinCell to bring this important treatment to market. This milestone is a testament to advancing our robust biopharmaceutical pipeline of innovative medicines that aim to support more people living with mental health disorders and neurological diseases in the coming years.”

Approximately 80% of patients with schizophrenia experience multiple relapses over the first five years of treatment,2 most commonly due to suboptimal adherence to treatment with oral antipsychotics. Each relapse carries a biological risk of loss of function, treatment refractoriness, and changes in brain morphology.3,4

Schizophrenia is a chronic, progressive and severely debilitating mental health disorder that affects how one thinks, feels and acts.5 This approval is based on data from two Phase 3 trials evaluating Uzedy in patients with schizophrenia: TV46000-CNS-30072 (the RISE Study – The Risperidone Subcutaneous Extended-Release Study) and TV46000-CNS-30078 (the SHINE Study – A Study to Test TV-46000 for Maintenance Treatment of Schizophrenia).

“The approval of the first product formulated with our technology is a pivotal moment for MedinCell and for the many patients who will benefit,” said Christophe Douat, CEO of MedinCell. “We are committed to supporting patients through innovative therapy options. It continues to be a wonderful journey with Teva, an ideal partner to harness the full potential of Uzedy. Our technology reaching commercial stage marks the start of an exciting new era for MedinCell and we are extremely proud to share this very special moment with all our employees and shareholders.”

The use of novel SteadyTeq technology in Uzedy controls the release of risperidone over time. The initiation of treatment requires no loading dose or oral supplementation. Therapeutic blood concentrations are reached within 6-24 hours of a single dose. 

“Treatments for schizophrenia are largely prescribed as daily oral medications, which can present challenges with adherence due to missed doses. Lack of adherence to treatment with oral antipsychotics is the most common cause of relapse in schizophrenia  so there’s a role for therapies that are dosed in one- or two-month dosing intervals to help prevent relapse,” said Christoph Correll, MD, professor of psychiatry at the Zucker School of Medicine, Hempstead, NY. “As a clinician, I am excited to now have a new treatment option that reduces the risk of relapse1 for this complex disease and helps address some of the barriers around receiving schizophrenia treatment.”

https://pubchem.ncbi.nlm.nih.gov/compound/Risperidone#section=2D-Structure

FDA Approves Uzedy (risperidone) Extended-Release Injectable Suspension for the Treatment of Schizophrenia in Adults

FDA Grants Accelerated Approval to Filspari (sparsentan) for the Reduction of Proteinuria in IgA Nephropathy

Travere Therapeutics, Inc. (Nasdaq: TVTX) announced  the U.S. Food and Drug Administration (FDA)  approval to Filspari™ (sparsentan) to reduce proteinuria in adults with primary IgAN at risk of rapid disease progression, generally a urine protein-to-creatinine ratio (UPCR) ≥1.5 g/g.

This indication is granted under accelerated approval based on reduction in proteinuria. It has not been established whether Filspari slows kidney function decline in patients with IgAN. The continued approval of Filspari may be contingent upon confirmation of a clinical benefit in the ongoing Phase 3 PROTECT Study, which is designed to demonstrate whether Filspari slows kidney function decline. Topline results from the two-year confirmatory endpoints in the PROTECT Study are expected in the fourth quarter of 2023 and are intended to support traditional approval of Filspari.

Filspari, a once-daily oral medication is designed to selectively target two critical pathways in the disease progression of IgAN (endothelin-1 and angiotensin II), and is the first and only non-immunosuppressive therapy approved for the treatment of this condition. IgAN is a rare kidney disease (RKD) and a leading cause of kidney failure due to glomerular disease, affecting up to 150,000 people in the U.S., with approximately 30,000 to 50,000 of such patients estimated to be addressable under the indication approved via accelerated approval. The Company expects Filspari to be available beginning the week of February 27, 2023, and will be providing a comprehensive patient support program throughout the patient’s treatment journey.

“The accelerated approval of Filspari is a significant milestone on our path to advancing a transformative treatment for the IgA nephropathy community,” said Eric Dube, Ph.D., president and chief executive officer, Travere Therapeutics. “As a first-of-its-kind, non-immunosuppressive therapy, we believe Filspari has the potential to ultimately become the new standard of care for IgA nephropathy and offer hope to those living with this condition who until now have had few treatment options. We are grateful to the patients, caregivers, clinical trial investigators, healthcare providers, and advocates who have worked alongside us to develop this innovative first-in-class therapy.”

“Today’s approval of Filspari sets the stage for a new standard of care for IgA nephropathy patients. A high proportion of individuals diagnosed with this disease do not sufficiently respond to the historical standard treatment, which has been therapies that are not indicated for IgA nephropathy. These treatments include hypertension drugs such as angiotensin-receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors and systemic glucocorticoids. As a result, many patients have struggled to manage their disease and have progressed more quickly to kidney failure,” said Dr. Brad Rovin, MD, Medical Director at Ohio State University Center for Clinical Research Management, Director of the Division for Nephrology, and steering committee member for the PROTECT clinical trial. “The approval of this innovative treatment is founded in data from the largest head-to-head Phase 3 clinical trial in IgA nephropathy. It is exciting to see that adult patients who are at risk of rapid disease progression, many of whom have waited a very long time for a treatment like this, now have hope for a better future.”

The approval of Filspari, granted under the FDA’s accelerated approval pathway, is based on clinically meaningful and statistically significant improvements in proteinuria compared to an active comparator in the pivotal and ongoing Phase 3 PROTECT Study, the largest head-to-head interventional study to date in IgAN. The PROTECT Study is a global, randomized, multicenter, double-blind, active-controlled clinical trial evaluating the safety and efficacy of 400 mg of Filspari, compared to 300 mg of irbesartan, in 404 patients ages 18 years and up with IgAN and persistent proteinuria despite maximal tolerated ACE or ARB therapy.  

https://en.wikipedia.org/wiki/Sparsentan

FDA Grants Accelerated Approval to Filspari(sparsentan) for the Reduction of Proteinuria in IgA Nephropathy

FDA Approves Veozah (fezolinetant) for the Treatment of Vasomotor Symptoms Due to Menopause

Astellas Pharma Inc. announced  the U.S. Food and Drug Administration (FDA)   approval of  Veozah (fezolinetant) 45 mg once daily for the treatment of moderate to severe vasomotor symptoms (VMS) due to menopause  on May 12. Veozah is the first nonhormonal neurokinin 3 (NK3) receptor antagonist approved to treat VMS due to menopause.

“Today’s approval of fezolinetant is a significant and, I believe, long awaited milestone for individuals in the U.S. who experience moderate to severe vasomotor symptoms during the menopausal transition,” said Genevieve Neal-Perry, M.D., Ph.D., Chair, UNC School of Medicine Department of Obstetrics and Gynecology. “This therapy is based on our understanding of the biology behind hot flashes. I’m excited to know that patients will have the option to choose this nonhormonal treatment.”

Before menopause, there is a balance between estrogens (hormones made by a woman’s ovaries) and neurokinin B (NKB), a brain chemical. This balance regulates the body’s temperature control center located in a specific area of the brain. As the body goes through menopause, estrogens decline and this balance is disrupted. This imbalance can lead to very uncomfortable symptoms called VMS. Veozah helps to restore the balance by blocking NKB in the temperature control center to reduce the number and intensity of hot flashes.

“Veozah uses a novel mechanism of action to target the root cause of VMS due to menopause,” said Marci English, Vice President and Head of BioPharma Development, Astellas. “FDA approval of this new treatment for moderate to severe VMS due to menopause is a testament to Astellas’ commitment to delivering innovative therapies in areas of unmet need that have been underserved, including women’s health.”

The approval is supported by results from the BRIGHT SKY™ program, which included three Phase 3 clinical trials as part of a development program that collectively enrolled over 3,000 individuals across the U.S., Canada and Europe. Results from the SKYLIGHT 1™ and SKYLIGHT 2™ pivotal trials characterize the efficacy and safety of fezolinetant for the treatment of moderate to severe VMS due to menopause. Data from the SKYLIGHT 4™ safety study further characterizes the long-term safety profile of fezolinetant.

VMS, characterized by hot flashes and/or night sweats, are common symptoms of menopause. VMS are the most common symptoms of menopause for which women seek treatment. In the U.S., about 60% to 80% of women experience these symptoms during or after the menopausal transition. VMS can have a disruptive impact on women’s daily activities and overall quality of life.

“Today’s approval of fezolinetant is a significant and, I believe, long awaited milestone for individuals in the U.S. who experience moderate to severe vasomotor symptoms during the menopausal transition,” said Genevieve Neal-Perry, M.D., Ph.D., Chair, UNC School of Medicine Department of Obstetrics and Gynecology. “This therapy is based on our understanding of the biology behind hot flashes. I’m excited to know that patients will have the option to choose this nonhormonal treatment.”

Before menopause, there is a balance between estrogens (hormones made by a woman’s ovaries) and neurokinin B (NKB), a brain chemical. This balance regulates the body’s temperature control center located in a specific area of the brain. As the body goes through menopause, estrogens decline and this balance is disrupted. This imbalance can lead to very uncomfortable symptoms called VMS. Veozah helps to restore the balance by blocking NKB in the temperature control center to reduce the number and intensity of hot flashes.

“Veozah uses a novel mechanism of action to target the root cause of VMS due to menopause,” said Marci English, Vice President and Head of BioPharma Development, Astellas. “FDA approval of this new treatment for moderate to severe VMS due to menopause is a testament to Astellas’ commitment to delivering innovative therapies in areas of unmet need that have been underserved, including women’s health.”

The approval is supported by results from the BRIGHT SKY™ program, which included three Phase 3 clinical trials as part of a development program that collectively enrolled over 3,000 individuals across the U.S., Canada and Europe. Results from the SKYLIGHT 1™ and SKYLIGHT 2™ pivotal trials characterize the efficacy and safety of fezolinetant for the treatment of moderate to severe VMS due to menopause. Data from the SKYLIGHT 4™ safety study further characterizes the long-term safety profile of fezolinetant.

Ref : https://en.wikipedia.org/wiki/Fezolinetant

FDA Approves Veozah (fezolinetant) for the Treatment of Vasomotor Symptoms Due to Menopause

BioLineRx Announces Submission of New Drug Application (NDA) to FDA for Motixafortide in Stem Cell Mobilization

BioLineRx Ltd.  announced the  submission of  its New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for Motixafortide in stem cell mobilization (SCM) for autologous bone marrow transplantation for multiple myeloma patients.

The NDA submission is based on the overwhelmingly positive top-line results from BioLineRx's GENESIS Phase 3 trial of Motixafortide on top of G-CSF (versus placebo on top of G-CSF) in stem cell mobilization for autologous bone marrow transplantation in multiple myeloma patients. The study met all primary and secondary endpoints with a very high degree of statistical significance (p<0.0001). The combination was also found to be safe and well tolerated.

"The submission of our first NDA is a significant milestone for our Company and gives us potential line of sight towards launching a product that we successfully developed for an indication in substantial need of more effective treatment options," stated Philip Serlin, Chief Executive Officer of BioLineRx. "Notably, ~90% of multiple myeloma patients in the GENESIS study went directly to transplantation after mobilizing the optimal number of stem cells following only one administration of Motixafortide and in only one apheresis session, compared to less than 10% of those receiving G-CSF alone. This high success rate has a substantial clinical benefit, especially when considering that new induction treatments are more effective than ever before but cause subsequent difficulty in mobilizing the target number of stem cells for transplantation. The high success rate may also confer significant benefits to transplant institutions through the more efficient use of apheresis units, where there is often a lack of available machines."

"The totality of data that we have compiled for Motixafortide in stem cell mobilization – both clinical and pharmacoeconomic – suggest that Motixafortide, if approved, can quickly become the key component of a new standard of care on top of G-CSF for all multiple myeloma patients undergoing autologous stem cell transplantation. The submission of our NDA brings us one critical step closer to that goal, and we look forward to working closely with the FDA during its review process," Mr. Serlin concluded.

The FDA's decision on acceptance of BioLineRx's NDA filing is expected in November. Assuming the filing is accepted, the potential PDUFA date would be in Q2 2023 (under a priority review process, if applicable) or Q3 2023 (under a standard review process). As BioLineRx finalizes its commercialization plans for Motixafortide in the U.S., the Company continues to advance critical pre-launch activities, required under any commercialization scenario, to ensure a robust and targeted commercial launch very soon after its PDUFA date, assuming FDA approval.

https://pubchem.ncbi.nlm.nih.gov/compound/Motixafortide

https://go.drugbank.com/drugs/DB14939

FDA Approves Apretude

 

ViiV Healthcare, the global specialist HIV company majority owned by GlaxoSmithKline plc (GSK), with Pfizer Inc. (Pfizer) and Shionogi Limited (Shionogi) as shareholders,  announced the US Food and Drug Administration (FDA) approval of Apretude, the first and only long-acting injectable pre-exposure prophylaxis (PrEP) option to reduce the risk of sexually acquired HIV-1. The long-acting injectable was approved for use in adults and adolescents weighing at least 35 kg who are at risk of sexually acquiring HIV and who have a negative HIV-1 test prior to initiation. The medicine was studied in men who have sex with men, as well as women and transgender women who have sex with men, who were at increased risk of sexually acquiring HIV.

Cabotegravir long-acting for PrEP is provided as an injection given as few as six times per year and is initiated with a single 600 mg (3-ml) injection given one month apart for two consecutive months. After the second initiation injection, the recommended continuation injection dose is a single 600 mg (3-ml) injection given every two months. Vocabria (cabotegravir oral tablets) may be administered for approximately one month before initiating the first injection to assess the tolerability of the medicine.

Deborah Waterhouse, CEO, ViiV Healthcare, said: “People who are vulnerable to acquiring HIV, especially those in Black and Latinx communities who are disproportionately impacted in the US, may want options beyond daily oral pills. That’s why ViiV Healthcare is proud that Apretude was studied in one of the most diverse and comprehensive HIV prevention trial programs to date, which also included some of the largest numbers of transgender women and Black men who have sex with men ever enrolled in an HIV prevention trial. With Apretude, people can reduce the risk of acquiring HIV with as few as six injections a year. Today’s approval is the latest example of ViiV Healthcare’s commitment to developing long-acting medicines that offer consumers a different choice.”

US FDA approval is based on the results from two international phase IIb/III multicenter, randomised, double-blind, active-controlled trials, HPTN 083 and HPTN 084, which evaluated the safety and efficacy of cabotegravir long-acting for PrEP in HIV-negative men who have sex with men, transgender women, and cisgender women, who were at increased risk of sexually acquiring HIV. In these trials, which included more than 7,700 participants across 13 countries combined, the blinded, randomised portions of both trials were stopped early by an independent Data Safety Monitoring Board after cabotegravir long-acting for PrEP was shown to be superior to daily oral emtricitabine/tenofovir disoproxil fumarate (TDF/FTC) tablets in preventing the acquisition of HIV in study participants. Clinical trial participants who received cabotegravir long-acting for PrEP experienced a 69% lower incidence of HIV compared to FTC/TDF tablets in HPTN 083 and a 90% lower incidence of HIV compared to FTC/TDF tablets in HPTN 084.

The most common adverse reactions (all grades) observed in at least 1% of clinical trial participants receiving cabotegravir long-acting for PrEP were injection site reactions, diarrhoea, headache, pyrexia, fatigue, sleep disorders, nausea, dizziness, flatulence, abdominal pain, vomiting, myalgia, rash, decreased appetite, somnolence, back pain, and upper respiratory tract infection. Adverse events led to discontinuation in 6% of participants in HPTN 083 and 1% of participants in HPTN 084.

In HPTN 083, participants in the US were inclusive of the Black/African American and Latinx communities of men and transgender women who have sex with men, who are disproportionately affected by the HIV epidemic and comprise the greatest percentage of new HIV diagnoses. In HPTN 084, all participants were cisgender women from sub-Saharan Africa. Women in this region bear a disproportionate burden of the HIV epidemic and may be twice as likely to acquire HIV as their male counterparts.

Richard Elion, MD, Director of Research at Washington Health Institute, said: “We have the tools to end the HIV epidemic through the implementation of effective antiretroviral treatment and HIV prevention. PrEP has played a vital role in protecting people from acquiring HIV. With the availability of cabotegravir long-acting for PrEP as an injection every two months to prevent HIV, people now have an important new option besides daily medication. This long-acting medication offers more options for prevention, and now providers and patients will be empowered by choices and the ability to choose the approach that is optimal for each individual.”

HIV continues to be a global public health crisis, with an estimated 38 million people living with HIV worldwide and 1.7 million new cases annually. PrEP represents an effective tool to reduce new cases of HIV, which in addition to successful HIV antiretroviral treatment, will help efforts to end the HIV epidemic. However, fewer than 25% of the people who could benefit from PrEP in the US are currently taking it. Despite the wide availability of daily oral PrEP, it can be limited by inconsistent adherence as well as structural and cultural barriers that lead to underutilisation in key populations.

https://www.drugs.com/apretude.html

https://www.drugs.com/newdrugs/fda-approves-apretude-cabotegravir-extended-release-injectable-suspension-hiv-pre-exposure-5754.html

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Axsome Therapeutics Announces FDA Acceptance of New Drug Application for AXS-07 (meloxicam-rizatriptan) for the Acute Treatment of Migraine

 

In continuation of my update on meloxicam, 

Axsome Therapeutics, Inc.   that the U.S. Food and Drug Administration (FDA) has accepted for filing the Company’s New Drug Application (NDA) for AXS-07 for the acute treatment of migraine, and has set a Prescription Drug User Fee Act (PDUFA) target action date of April 30, 2022 for the NDA. AXS-07 (MoSEIC™ meloxicam-rizatriptan) is a novel, oral, rapidly absorbed, multi-mechanistic, investigational medicine for migraine.

  

meloxicam

 

Rizatriptan

  “The FDA’s acceptance of the NDA for AXS-07 is an important milestone for Axsome as it brings us closer to potentially making this multi-mechanistic treatment available to migraine patients in need,” said Herriot Tabuteau, MD, Chief Executive Officer of Axsome. “We look forward to continued interactions with the FDA during the review process.”

The NDA is supported by results from two Phase 3 randomized, double-blind, controlled trials of AXS-07 in the acute treatment of migraine, the MOMENTUM and INTERCEPT trials, which demonstrated statistically significant elimination of migraine pain with AXS-07 compared to placebo and active controls.

AXS-07 is a novel, oral, rapidly absorbed, multi-mechanistic investigational medicine for the acute treatment of migraine, consisting of MoSEIC™ meloxicam and rizatriptan. Meloxicam is a new molecular entity for migraine enabled by Axsome’s MoSEIC (Molecular Solubility Enhanced Inclusion Complex) technology, which results in rapid absorption of meloxicam while maintaining a long plasma half-life. Meloxicam is a COX-2 preferential non-steroidal anti-inflammatory drug and rizatriptan is a 5-HT1B/1D agonist. AXS-07 is designed to provide rapid, enhanced and consistent relief of migraine, with reduced symptom recurrence. AXS-07 is covered by more than 80 issued U.S. and international patents which provide protection out to 2036. AXS-07 is not approved by the FDA.

https://pubchem.ncbi.nlm.nih.gov/compound/Rizatriptan

https://pubchem.ncbi.nlm.nih.gov/compound/Meloxicam#section=2D-Structure

FDA Grants Tentative Approval for Liquidia’s Yutrepia (treprostinil) Inhalation Powder

 In continuation of my update on treprostinil

 

Liquidia Corporation  announced that, the U.S. Food and Drug Administration (FDA) has granted tentative approval for Yutrepia™ (treprostinil) inhalation powder, previously referred to as LIQ861. Yutrepia is indicated for the treatment of pulmonary arterial hypertension (PAH) to improve exercise ability in adult patients with New York Heart Association (NYHA) Functional Class II-III symptoms. Tentative approval indicates that Yutrepia has met all regulatory standards for quality, safety and efficacy required for approval in the United States.

 

Dr. Tushar Shah, Chief Medical Officer of Liquidia, said: “We would like to take the opportunity to thank the patients and investigators who participated in the clinical development of Yutrepia. The tentative approval for Yutrepia is another step toward providing an important option for patients with PAH in the U.S. We believe Yutrepia can improve the limitations of current nebulized therapies by allowing the administration of an expanded dose range of inhaled treprostinil using a proven, convenient, palm-sized device.”

The addressable market for inhaled treprostinil is significant and expected to grow. In 2020, United Therapeutics reported that its nebulized formulation of treprostinil indicated for PAH achieved sales of more than $480 million. The attributes of Yutrepia including ease-of-use, convenience, direct lung delivery, and higher dosage range may not only make Yutrepia a preference to nebulized therapy, but also an alternative to oral treatments, and possibly a treatment option to delay the use of parenteral therapies in PAH. There may also be future expansion opportunities for inhaled treprostinil into additional indications.

Damian deGoa, Chief Executive Officer of Liquidia added: “This is a significant milestone for Liquidia. We are really proud of our team. Not only does the tentative approval establish the safety and efficacy of Yutrepia for PAH patients but, in the process, we have validated our proprietary PRINT® technology to engineer discrete drug particles with uniform composition, size, and shape. There is more work to be done. We will now focus our efforts on pre-commercial launch activities and the growing market opportunity for Yutrepia in PAH and potential new indications.”

Due to a regulatory stay pursuant to the Drug Price Competition and Patent Term Restoration Act (Hatch-Waxman Act), Yutrepia cannot yet be marketed in the United States. In June 2020, United Therapeutics filed a lawsuit against Liquidia for alleged infringement of three patents related to Tyvaso®. As a result, the FDA cannot give final approval of Yutrepia until the expiration of the regulatory stay on October 27, 2022, or earlier resolution or settlement of the ongoing litigation.

About Yutrepia™(treprostinil) inhalation powder
Yutrepia is an investigational, inhaled dry powder formulation of treprostinil delivered through a proven, convenient, palm-sized device. On November 5, 2021, the FDA issued a tentative approval for Yutrepia, which is indicated for the treatment of pulmonary arterial hypertension (PAH) to improve exercise ability in adult patients with New York Heart Association (NYHA) Functional Class II-III symptoms. Yutrepia was designed using Liquidia’s PRINT® technology, which enables the development of drug particles that are precise and uniform in size, shape, and composition, and that are engineered for optimal deposition in the lung following oral inhalation. Liquidia has completed INSPIRE, or Investigation of the Safety and Pharmacology of Dry Powder Inhalation of Treprostinil, an open-label, multi-center phase 3 clinical study of Yutrepia in patients diagnosed with PAH who are naïve to inhaled treprostinil or who are transitioning from Tyvaso (nebulized treprostinil). Yutrepia was previously referred to as LIQ861 in investigational studies.

FDA Approves Xipere (triamcinolone acetonide injectable suspension) for the Treatment of Macular Edema Associated with Uveitis

In continuation of my update on triamcinolone .......

Biomedical,Inc., a biopharmaceutical company   announced  the U.S. Food and Drug Administration (FDA)   approval of  XIPERE™ (triamcinolone acetonide injectable suspension) for suprachoroidal use for the treatment of macular edema associated with uveitis, a form of eye inflammation.

"With this FDA approval, XIPERE™ is the first and only therapy available in the United States that utilizes the suprachoroidal space to treat patients suffering from macular edema associated with uveitis, which is the leading cause of vision loss in people with uveitis2. The utilization of the suprachoroidal space provides targeted delivery and compartmentalization of medication," said Joseph C. Papa, chairman and CEO, Bausch Health. "The approval of XIPERE™ exemplifies our commitment to bringing innovative new options to help patients improve their treatment journey. We expect to make XIPERE™ available during the first quarter of 2022."

"The suprachoroidal space is an untapped frontier in eye health. We are proud to be the pioneers in treating serious retinal diseases by implementing this novel, targeted approach. With this approval, we begin a new era in delivering therapies to the back of the eye," said George Lasezkay, Pharm.D., J.D., president and CEO, Clearside. "XIPERE™ is the first commercial product developed by Clearside, the first product approved for injection into the suprachoroidal space and the first therapy approved for macular edema associated with uveitis. Our unique approach now has the potential to positively impact this patient population, which previously had no other treatment options approved for this indication."

Macular edema is the buildup of fluid in the macula, which causes retinal swelling and distorted vision, and if left untreated, may lead to permanent vision loss. XIPERE™ is designed to treat macular edema associated with uveitis via suprachoroidal administration using the proprietary SCS Microinjector developed by Clearside. Suprachoroidal administration is an innovative technique for delivering ocular therapies that may facilitate more targeted delivery of therapeutic agents to the retina and choroid.

The SCS Microinjector® offers unique access to the back of the eye where sight-threatening disease often occurs. It is designed to provide targeted and compartmentalized delivery and higher proportions of absorption relative to intravitreal injection (IVT). Targeted drug delivery via the suprachoroidal space (SCS) may also limit corticosteroid exposure to the anterior segment5 with the potential to reduce the risk of certain adverse events, such as cataracts, intraocular pressure elevation and exacerbation of glaucoma, that are commonly associated with local delivery techniques.

"The safety and efficacy data of XIPERE™ was demonstrated in multiple clinical studies and its unique suprachoroidal administration approach provides exceptional access and high bioavailability to the posterior segment of the eye," said Steven Yeh, M.D., professor of ophthalmology and director of retinal disease and uveitis, Stanley M. Truhlsen Eye Institute, University of Nebraska Medical Center, and principal investigator for the XIPERE™ Phase 3 (PEACHTREE) pivotal study. "With the approval of XIPERE™, eye care professionals now have a new and innovative treatment option for their patients with macular edema associated with uveitis.".. More