FDA Approves Xelstrym (dextroamphetamine) Transdermal System for the Treatment of Attention-Deficit/Hyperactivity Disorder (ADHD)

Noven Pharmaceuticals, Inc., awholly-ownedsubsidiary of Hisamitsu Pharmaceutical Co., Inc., today announced that the U.S. Food and Drug Administration (FDA) has approved Xelstrym (dextroamphetamine) transdermal system, CII, for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) for adults and pediatric patients 6 years and older.1 Xelstrym is the first-and-only FDA-approved transdermal amphetamine patch.

The efficacy and safety of Xelstrym for the treatment of ADHD in pediatric patients 6 to 17 years was evaluated in a multi-center, randomized, double-blind,placebo-controlled,cross-over design, modified analog classroom study. The primary efficacy endpoint was observed as measured by the Swanson, Kotkin, Agler, M-Flynn, and Pelham Scale (SKAMP) total score demonstrating a significant separation from placebo with the use of Xelstrym. The most common adverse reactions (incidence ≥2% and greater than the rate for placebo) in pediatric patients 6 to 17 years treated with Xelstrym were decreased appetite, headache, insomnia, tic, abdominal pain, vomiting, nausea, irritability, blood pressure increased, and heart rate increased. The efficacy and safety of Xelstrym in adults was based on the comparable Xelstrym pharmacokinetic profile in adults and children, and the established bridge to adequate and well- controlled studies of lisdexamfetamine.

"The availability of Xelstrym underscores the need for a non-oral amphetamine treatment for ADHD," said Greg Mattingly, MD, Associate Clinical Professor of Psychiatry at The Washington University School of Medicine in St. Louis, Missouri. "As a once-daily transdermal patch, Xelstrym provides clinicians and their patients, many with varying daily schedules, the ability to share in the decision making process of determining when to apply and subsequently, when to remove the patch to optimize the desired benefit of individualized treatment."

Xelstrym should be applied 2 hours before an effect is needed and removed within 9 hours after application. Dose titration and final dosage should be individualized depending on clinical response and tolerability. Xelstrym will be available in dosage strengths of 4.5 mg/9 hours, 9 mg/9 hours, 13.5 mg/9 hours and 18 mg/9 hours.1

"FDA's approval of Xelstrym provides people living with ADHD a new option to manage a medication schedule that fits their individual lifestyle," said Joel Lippman, M.D., Chief Operating Officer and Chief Medical Officer, Noven Pharmaceuticals, Inc. "As the first amphetamine transdermal patch available for the treatment of ADHD in adults and pediatrics, this is a significant milestone for Noven and our goal of offering new options for clinicians, caregivers and patients for the treatment of ADHD. This approval enables our team to finalize preparations for commercial launch in the U.S. as early as the second half of this year."

https://reference.medscape.com/drug/ztalmy-ganaxolone-4000250

FDA Approves Ztalmy (ganaxolone) for Seizures Associated with CDKL5 Deficiency Disorder

Marinus Pharmaceuticals, Inc. (Nasdaq: MRNS), a pharmaceutical company dedicated to the development of innovative therapeutics to treat seizure disorders, today announced that the U.S. Food and Drug Administration (FDA) has approved Ztalmy® (ganaxolone) oral suspension for the treatment of seizures associated with cyclin-dependent kinase-like 5 deficiency disorder (CDD), a rare form of genetic epilepsy, in patients two years of age and older.1 Ztalmy, the first FDA approved treatment specifically in CDD, is a neuroactive steroid that acts as a positive allosteric modulator of the GABAA receptor. It is expected to be available through a designated specialty pharmacy in July 2022.

“Today is a historic milestone not only for Marinus but for CDD patients, families and caregivers who have long been navigating the unpredictable, often devastating reality of living with uncontrolled seizures,” said Scott Braunstein, M.D., Chief Executive Officer of Marinus. “The approval of Ztalmy would not have been possible without the patients, caregivers and investigators who participated in the clinical trials to develop this important new therapy. We are grateful and humbled by the opportunity to bring the first and only FDA-approved treatment for seizures associated with CDD to this community.

CDD is a serious and rare genetic disorder characterized by early‑onset, difficult‑to‑control seizures and severe neuro‑developmental impairment.2 It’s caused by a mutation of the cyclin-dependent kinase-like 5 (CDKL5) gene, located on the X chromosome. The CDKL5 gene produces a protein that is important for normal brain development and function. 3

“There has been a great unmet medical need for treatments that address seizures associated with CDKL5 deficiency disorder given their prominent role and profound impact on patients,” said Scott Demarest, M.D., Principal Investigator (PI) for the Marigold trial and neurologist and Clinical Director of Precision Medicine at Children’s Hospital Colorado. “To date, antiseizure treatment decisions have been based on very limited clinical evidence in this patient population and the resulting outcomes underscore the need for therapies that further improve seizure control. Thanks to our research and this trial, we now have the first treatment specifically approved for seizures associated with CDKL5 deficiency disorder that was shown to have a positive benefit-risk profile.” Dr. Demarest is also PI of the International CDKL5 Clinical Research Network and Assistant Professor of Pediatrics-Neurology at the University of Colorado School of Medicine.

The approval of Ztalmy in CDD is based on data from the Phase 3 Marigold double-blind placebo-controlled trial, in which 101 patients were randomized and individuals treated with Ztalmy showed a median 30.7% reduction in 28-day major motor seizure frequency, compared to a median 6.9% reduction for those receiving placebo, achieving the trial’s primary endpoint (p=0.0036). In the Marigold open label extension study, patients treated with Ztalmy for at least 12 months (n=48) experienced a median 49.6% reduction in major motor seizure frequency. In the clinical development program, Ztalmy demonstrated efficacy, safety and tolerability with the most common adverse reactions (incidence >/5% and at least twice the rate of placebo) in the Ztalmy group being somnolence, pyrexia, salivary hypersecretion and seasonal allergy.

“As the mother of a daughter living with CDD, I’ve experienced first-hand the devastating impact seizures can have on these patients,” said Karen Utley, President and Co-founder of the International Foundation for CDKL5 Research. “This approval is monumental for the CDD community—bringing not only the first approved treatment option specifically for CDD patients, but renewed hope to those who have struggled to find medications that are effective in significantly reducing the number of seizures these patients experience on a daily basis.

Ztalmy is expected to be commercially available in the U.S. in July following scheduling by the U.S. Drug Enforcement Administration. To support the CDD community, Marinus plans to launch The Ztalmy One™ Program, a comprehensive patient services program to provide assistance with product access, ongoing support to patients, caregivers and their medical teams, and financial support to eligible patients.

The FDA reviewed Ztalmy under Priority Review and granted Ztalmy orphan drug and Rare Pediatric Disease designations for the treatment of CDD. With the approval, the FDA awarded a Rare Pediatric Disease Priority Review Voucher (PRV), which Marinus plans to monetize.

https://draft.blogger.com/blog/posts/6520560265126950473?hl=en-GB&q=Ztalmy%20(ganaxolone)

FDA Approves Ztalmy (ganaxolone) for Seizures Associated with CDKL5 Deficiency Disorder

FDA Approves Igalmi (dexmedetomidine) Sublingual Film for Acute Treatment of Agitation Associated with Schizophrenia or Bipolar I or II Disorder in Adults

BioXcel Therapeutics, Inc., a biopharmaceutical company utilizing artificial intelligence (AI) approaches to identify and develop transformative medicines in neuroscience and immuno-oncology,  announced  the U.S. Food and Drug Administration (FDA)   approval of  Igalmi™ (dexmedetomidine) sublingual film for the acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults. Igalmi can be self-administrated by patients under the supervision of a healthcare provider. The Company is prepared to launch Igalmi in the U.S. in the second quarter of 2022.

“There are large numbers of patients who experience agitation associated with schizophrenia and bipolar disorders, and this condition has been a long-standing challenge for healthcare professionals to treat,” said Dr. John Krystal, M.D., the Robert L. McNeil, Jr. Professor of Translational Research and Chair of the Department of Psychiatry at Yale School of Medicine. “The approval of Igalmi, a self-administered film with a desirable onset of action, represents a milestone moment. It provides healthcare teams with an innovative tool to help control agitation. As clinicians, we welcome this much-needed new oral treatment option.”

An estimated 7.3 million people in the U.S. are diagnosed with schizophrenia or bipolar disorders. Up to a quarter of these people experience agitation, with episodes that can occur 10 to 17 times annually, totaling up to 25 million agitation episodes for these two patient populations per year. Agitation episodes are associated with a significant burden for patients, caregivers, and the healthcare system.

“Igalmi is the first new acute treatment for schizophrenia or bipolar disorder-associated agitation in nearly a decade and represents a differentiated approach to helping patients manage this difficult and debilitating symptom,” said Vimal Mehta, Ph.D., CEO of BioXcel Therapeutics. “With this landmark achievement of our first approved drug, we have taken a monumental step toward our mission of bringing transformative medicines in neuroscience to patients using our AI platform. We are deeply grateful to our clinical trial participants, healthcare providers, researchers, and employees for contributing to this important new therapy. We believe Igalmi has significant market-changing potential, and we are excited to execute on our commercial launch plans in the U.S. this quarter.”

The FDA approval of Igalmi is based on data from two pivotal randomized, double-blinded, placebo-controlled, parallel group Phase 3 trials evaluating Igalmi for the acute treatment of agitation associated with schizophrenia (SERENITY I) or bipolar I or II disorder (SERENITY II).

The primary endpoint was the mean change from baseline in the Positive and Negative Syndrome Scale-Excited Component (PEC) total score assessed at 2 hours following dosing. The key secondary endpoint was the earliest time where efficacy, measured by the change from baseline in PEC score, was statistically separated from placebo. PEC is an investigator-rated instrument for measuring agitation in patients that evaluates five elements associated with agitation: poor impulse control, tension, hostility, uncooperativeness, and excitement.

In both trials, Igalmi met the primary endpoint at two hours after the first dose in patients treated with the 120 mcg and 180 mcg doses, demonstrating statistically significant improvements from baseline. Igalmi also met the key secondary endpoint, demonstrating a rapid onset of action, with statistically significant separation from placebo observed at 20 minutes for both the 180 mcg and 120 mcg doses in SERENITY II and 20 minutes and 30 minutes in SERENITY I, respectively.

The most common adverse reactions (incidence ≥5% and at least twice the rate of placebo) were somnolence (drowsiness and feeling sleepy), paresthesia or oral hypoesthesia, dizziness, dry mouth, hypotension (low blood pressure) and orthostatic hypotension. All adverse drug reactions were mild to moderate in severity. While Igalmi did not exhibit any treatment-related serious adverse effects (SAEs) in Phase 3 studies, it may cause notable side effects including hypotension, orthostatic hypotension and bradycardia, QT interval prolongation, and somnolence.

Data from the pivotal Phase 3 SERENITY II trial evaluating Igalmi in bipolar disorders were published in the Journal of the American Medical Association (JAMA) on February 22, 2022.

About Agitation Associated with Schizophrenia and Bipolar Disorder

Agitation is a common and difficult-to-manage symptom associated with bipolar I or II or schizophrenia. Early identification and prompt intervention to relieve agitation are essential to avoid symptomatic escalation and the emergence of aggression. Expert consensus best-practice guidelines have recommended that agitation should be treated by a combination of behavioral calming techniques, verbal de-escalation, and medications that are voluntarily accepted by patients without coercion. The goal of using medication is to calm the patient so that he or she can be more accurately assessed by clinicians. Medication used in this manner is consistent with current guidelines, which state that the proper endpoint of medication administration is calming without inducing sleep. This approach may help avoid the costly and traumatic use of coercive techniques like physical restraint and seclusion, which may result in admission and prolonged hospitalization.

FDA Approves Epsolay (benzoyl peroxide) Cream for the Treatment of Rosacea

Sol-Gel Technologies, Ltd. a dermatology company focused on identifying, developing and commercializing branded and generic topical drug products for the treatment of skin diseases, announced today the Food and Drug Administration (FDA) approval of its drug product, Epsolay, a proprietary cream formulation of benzoyl peroxide, 5%, for the treatment of inflammatory lesions of rosacea in adults.

The benzoyl peroxide in Epsolay is encapsulated within silica-based patented microcapsules. The silica-based shell is designed to slowly release benzoyl peroxide over time to provide a favorable efficacy and safety profile. The approval of Epsolay is supported by data from two positive, identical Phase 3 randomized, double-blind, multicenter, 12-week, clinical trials that evaluated the safety and efficacy of Epsolay compared to vehicle in people with inflammatory lesions of rosacea (N = 733). The coprimary endpoints in both trials were the proportion of subjects with treatment success and the absolute change from baseline in lesion counts at Week 12. Epsolay was more effective than vehicle cream on the co-primary efficacy endpoints starting from 4 weeks of treatment in both trials. With Epsolay treatment, inflammatory lesions of rosacea were reduced by nearly 70% by the end of both 12-week trials vs. 38-46% with vehicle. Nearly 50% of subjects were ‘clear’ (IGA=0) or ‘almost clear’ (IGA=1) at 12 weeks vs. 38-46% with placebo. Post-hoc analysis of lesion count and IGA success at Week 2 confirmed a significantly greater treatment effect for Epsolay relative to vehicle as early as Week 2. In the open-label extension, 73% of subjects were ‘clear’ (IGA=0) or ‘almost clear’ (IGA=1) at 52 weeks (N = 547).

Sol-Gel has granted to Galderma Holding SA (“Galderma”) the exclusive rights to commercialize Epsolay in the United States. Founded in 1981, Galderma is the world’s largest independent dermatology company.

“Having Epsolay approved by the FDA is a watershed moment for the 16 million people in the United States suffering from rosacea,” stated Alon Seri-Levy, PhD, Chief Executive Officer of Sol-Gel. “Based on the robust clinical data, we believe that Epsolay has the potential to change the treatment landscape. We are proud to have Galderma as our partner to launch this drug since Galderma has an unparalleled track record of introducing innovative drugs in the United States’ rosacea market,” said Dr. Seri-Levy.

Neal D. Bhatia. M.D., dermatologist at Therapeutics Clinical Research in San Diego, California, commented, “There is poor adherence of my patients to current treatments for inflammatory rosacea and I look forward to being able to prescribe Epsolay to them, primarily because Epsolay has demonstrated outstanding and rapid efficacy results and also because Epsolay has been shown to be well-tolerated, both of which are important factors to ensure patients' satisfaction.”

”Galderma is committed to delivering innovation in dermatology so that healthcare professionals and their patients have the products they need,” said Baldo Scassellati Sforzolini, M.D., Ph.D., Global Head of Research & Development at Galderma. “People with rosacea experience a significant burden of disease with diminished quality of life and the approval of Epsolay represents an important advancement for those who are living with rosacea. We are pleased to be able to launch Epsolay and look forward to bringing this new treatment option to the United States.”

FDA Approves Vijoice (alpelisib) for the Treatment of PIK3CA-Related Overgrowth Spectrum (PROS)

Novartis  announced  the U.S. Food and Drug Administration (FDA) granting  accelerated approval to Vijoice® (alpelisib) for the treatment of adult and pediatric patients 2 years of age and older with severe manifestations of PIK3CA-Related Overgrowth Spectrum (PROS) who require systemic therapy. Vijoice is the first FDA-approved treatment for PROS, a spectrum of rare conditions characterized by overgrowths and blood vessel anomalies impacting an estimated 14 people per million.2,3 In accordance with the Accelerated Approval Program, continued approval may be contingent upon verification and description of clinical benefit from confirmatory evidence.

“Today’s approval of the first treatment for PROS offers hope for a better quality of life to patients and families affected by these rare conditions,” said Kristen Davis, Executive Director of CLOVES Syndrome Community. “PROS conditions can be debilitating and disabling and can result in disruptions to everyday activities. Until today, often the only treatment options for patients were surgical or interventional radiology procedures.”

PROS conditions can affect quality of life and pose a range of physical, emotional and social challenges for patients and their families, ranging from functional impacts and developmental delays to chronic pain, mobility issues, and feelings of isolation. PROS management can be challenging, requiring collaboration from a multidisciplinary team, and patients and physicians have only had access to interventions focused on symptom management.

“I am proud of this outstanding achievement for the PROS community. The EPIK-P1 study results build on our earlier pre-clinical findings and demonstrate the efficacy of Vijoice for select PROS conditions, effectively reducing PROS growths,” said Guillaume Canaud, MD, PhD, Necker-Enfants Malades Hospital – AP-HP, the Paris Descartes University, Inserm (INEM Institute Necker Enfants Malades – Centre for Molecular Medicine). “This is a significant advancement in therapy for PROS with the potential to positively change the treatment trajectory and outcomes for patients.”

FDA approval was based on real-world evidence from EPIK-P1, a retrospective chart review study that showed patients treated with Vijoice experienced reduced target lesion volume and improvement in PROS-related symptoms and manifestations. The primary endpoint analysis conducted at week 24 showed 27% of patients (10/37) achieved a confirmed response to treatment, defined as 20% or greater reduction in the sum of PROS target lesion volume. Nearly three in four patients with imaging at baseline and week 24 (74%, 23/31) showed some reduction in target lesion volume, with a mean reduction of 13.7%, and no patients experienced disease progression at time of primary analysis. Additionally, at week 24, investigators observed patient improvements in pain (90%, 20/22), fatigue (76%, 32/42), vascular malformation (79%, 30/38), limb asymmetry (69%, 20/29), and disseminated intravascular coagulation (55%, 16/29). These improvements were observed in subsets of patients across the study population (n=57) who reported symptoms at baseline and at week 24.

“The approval of Vijoice marks a turning point for patients who, until now, have not had an approved therapy to specifically address their disease,” said Victor Bulto, President, Novartis Innovative Medicines US. “We are grateful to the physicians, patients and families who participated in the EPIK-P1 trial. We are continuing to invest in studies to advance the scientific understanding of PROS conditions and to understand the full potential of Vijoice.”

In EPIK-P1, the most common adverse events (AEs) of any grade were diarrhea (16%), stomatitis (16%), and hyperglycemia (12%). The most common grade 3/4 AE was cellulitis (4%); one adult case was considered treatment-related

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

FDA Approves Leqvio (inclisiran), First-in-Class siRNA to Reduce Low-Density Lipoprotein Cholesterol (LDL-C)

                       In continuation of my update on inclisiran

                             Novartis today announced the US Food and Drug Administration (FDA) approval of Leqvio® (inclisiran), the first and only small interfering RNA (siRNA) therapy to lower low-density lipoprotein cholesterol (also known as bad cholesterol or LDL-C) with two doses a year, after an initial dose and one at three months.

"Leqvio is a revolutionary approach to lower LDL-C, and creates new possibilities for how  healthcare systems can impact cardiovascular disease, a defining public health challenge of our time," said Vas Narasimhan, Novartis CEO. "We now have the opportunity, working together with partners, to provide this first-ever approved LDL-C–lowering siRNA-based therapy to tackle ASCVD at scale across the United States."

Leqvio is indicated in the United States as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with clinical atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) who require additional lowering of LDL-C. The effect of Leqvio on cardiovascular morbidity and mortality is being explored in clinical trials currently underway.

"ASCVD is a substantial public health burden affecting 30 million Americans," said Norman Lepor, MD, a Los Angeles based cardiologist and a clinical investigator in the Phase III clinical program for Leqvio. "As a first-of-its-kind siRNA therapy, Leqvio works differently than other cholesterol treatments, with twice-yearly dosing that makes it a compelling option for the millions of people with ASCVD already on cholesterol-lowering medications struggling to reach their LDL-C target."

Leqvio reduces the amount of LDL-C in the bloodstream by improving the liver's natural ability to prevent the production of a protein that plays a role in keeping circulating cholesterol levels high6,7. It is a subcutaneous injection given by a healthcare provider with an initial dose, then again at three months, and then every six months1. This approach may help those who have trouble sticking to medicines that are self-administered and have greater dosing frequency. Leqvio will be available in early January 2022.

"People with ASCVD have most likely experienced a heart attack or stroke from high cholesterol, causing a burden on the family and having a negative impact on lives," said Andrea Baer, Executive Director of The Mended Hearts, Inc. "One of the first steps to improving patients' health is to manage high cholesterol and we're encouraged that this new twice-a-year treatment offers a new option." 

The FDA approval was based on results from the comprehensive Phase III ORION-9, -10 and -11 clinical trials, in which all 3,457 participants with ASCVD or HeFH had elevated LDL-C while receiving a maximally tolerated dose of statin therapy2,3. In the Phase III trials at month 17, Leqvio delivered effective and sustained LDL-C reduction of up to 52% vs. placebo and was reported to be well-tolerated with a safety profile shown to be comparable to placebo2,3. The most common side effects were mild to moderate injection site reaction (including pain, redness and rash), joint pain, urinary tract infection, diarrhea, chest cold, pain in legs or arms and shortness of breath2,3.

Novartis has obtained global rights to develop, manufacture and commercialize Leqvio under a license and collaboration agreement with Alnylam Pharmaceuticals, a leader in RNAi therapeutics.

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

FDA Approves Recorlev (levoketoconazole) for the Treatment of Endogenous Hypercortisolemia in Adult Patients With Cushing’s Syndrome

Xeris Biopharma Holdings, Inc. (Nasdaq: XERS), announce  the U.S. Food and Drug Administration (FDA) approval of Recorlev® (levoketoconazole) for the treatment of endogenous hypercortisolemia in adult patients with Cushing’s syndrome for whom surgery is not an option or has not been curative.

“We are thrilled with the FDA's approval of Recorlev as a safe and effective treatment option for patients with endogenous Cushing's syndrome. With this approval, Xeris’ experienced endocrinology-focused commercial organization can begin rapidly working to help address the needs of Cushing’s syndrome patients in the U.S. who are treated with prescription therapy,” said Paul R. Edick, Chairman and CEO of Xeris Biopharma. “Today’s announcement also reinforces the value that we saw in acquiring Strongbridge Biopharma’s attractive rare disease portfolio, which we believe will deliver compelling long-term value to our shareholders. We look forward to making Recorlev commercially available in the first quarter.”

The approval of Recorlev was based upon safety and efficacy data from two positive Phase 3 studies that evaluated a combined study population of 166 patients, which was representative of the adult drug-treated U.S. population with Cushing’s syndrome. The SONICS study met its primary and key secondary endpoints, significantly reducing and normalizing mean urinary free cortisol concentrations without a dose increase. LOGICS, a double-blind, placebo-controlled randomized-withdrawal study that met its primary and key secondary endpoints, confirmed the efficacy and safety of Recorlev in normalizing and maintaining therapeutic response compared with placebo.

“Levoketoconazole (Recorlev) is an important and welcome new therapeutic option for clinicians to help manage patients with endogenous Cushing's syndrome, a severe, potentially life-threatening rare disease, if not appropriately treated, with multisystem signs and symptoms,” said Maria Fleseriu, M.D., FACE, professor of Medicine and Neurological Surgery and director of the Pituitary Center at Oregon Health Sciences University. “In prospective clinical studies, treatment with levoketoconazole was shown to be effective for reducing and normalizing cortisol.”

“Cushing’s syndrome is a rare disease that can be physically and emotionally devastating to the patient. Most patients endure years of symptoms prior to obtaining a diagnosis and are then faced with limited effective treatment options," said Leslie Edwin, president of the Cushing’s Support & Research Foundation. “Today we are excited to see that the long and complicated path of rare drug development has reached FDA approval on a new therapeutic option for our underserved Cushing's community. We are grateful that the researchers worked so diligently for so long to establish the safety and efficacy of this drug. Rare disease patients know the importance of sharing their complicated experiences as ‘expert witnesses’, and we thank Xeris for being an early adherent to this concept. We especially want to thank the clinical trial patients who made this progress possible.”

Xeris is committed to ensuring everyone who needs access to their therapies will receive it. Xeris has created Xeris CareConnection™ to provide a comprehensive program for patients and their caregivers throughout the treatment journey, including financial assistance, one-on-one support, and educational resources. Xeris CareConnection also supports healthcare professionals and their teams through education on access and reimbursement. To get started with Recorlev, reach out to Xeris CareConnection (available Monday–Friday from 8 a.m–7 p.m ET) at 1-844-444-RCLV (7258).

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

https://reference.medscape.com/drug/recorlev-levoketoconazole-4000226

FDA Approves Quviviq (daridorexant) for the Treatment of Adults with Insomnia

Idorsia Ltd (SIX: IDIA) announced  the US Food and Drug Administration (FDA)  approval of  Quviviq (daridorexant) 25 mg and 50 mg for the treatment of adult patients with insomnia, characterized by difficulties with sleep onset and/or sleep maintenance1. The FDA approval of Quviviq is based on an extensive clinical program that included 1,854 adults with insomnia at over 160 clinical trial sites across 18 countries. Insomnia, a serious medical condition, is the most common sleep disorder in the US.

Quviviq is a dual orexin receptor antagonist, which blocks the binding of the wake-promoting neuropeptides orexins and is thought to turn down overactive wakefulness, as opposed to treatments that generally sedate the brain.

During the Phase 3 clinical program, Quviviq demonstrated significant improvement versus placebo on objective measures of sleep onset and sleep maintenance, and patient reported total sleep time. Consistent with the US prescribing information, the 50 mg dose of Quviviq, which was evaluated in one of the two pivotal studies, demonstrated a significant reduction in patient reported daytime sleepiness, using a validated instrument. The most common adverse reactions (in at least 5% of patients and greater than placebo) were headache (placebo: 5%, 25 mg: 6%, 50 mg: 7%,) and somnolence or fatigue (placebo: 4%, 25 mg: 6%, 50 mg: 5%).

The FDA has recommended that Quviviq be classified as a controlled substance and it is anticipated to be available to patients in May 2022, following scheduling by the US Drug Enforcement Administration.

Martine Clozel, MD and Chief Scientific Officer of Idorsia, commented:

“After more than 20 years of research and a progressive understanding of the role of orexin in sleep-wake balance and of the potential of orexin receptor antagonism, we designed daridorexant to help address several issues people with insomnia face. Daridorexant properties include a potent inhibition of both orexin receptors, a rapid absorption for sleep onset, and a pharmacokinetic profile such that around 80% of daridorexant has been eliminated after a night of sleep to help minimize residual effects.”

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

https://clinicaltrials.gov/ct2/show/NCT04250506

FDA Approves Ryaltris (mometasone and olopatadine) Nasal Spray for Seasonal Allergic Rhinitis

In continuation of my update on olopatadine

Glenmark Pharmaceuticals Limited, announced the  FDA approval of its New Drug Application (NDA) for Ryaltris, an innovative, fixed- dose (metered), prescription, combination drug product nasal spray for the treatment of symptoms of Seasonal Allergic Rhinitis in adults and pediatric patients 12 years of age and older in the United States.

mometasone

Olopatadine,

The FDA's approval of Ryaltris™ represents a major milestone for Glenmark and clearly supports our efforts to bring innovative treatment options in our key therapeutic areas," said Robert Crockart, Chief Commercial Officer of Glenmark Pharmaceuticals Limited. "With this NDA approval, we look forward to bringing this new medicine to physicians and their patients for the treatment of symptoms of seasonal allergic rhinitis, including nasal and ocular symptoms."

Ryaltris™ will be marketed and distributed in the United States (US) by Hikma Specialty U.S.A., Inc., as part of its exclusive licensing agreement with Glenmark Specialty S.A (Switzerland).

Ryaltris is a metered, fixed-dose, aqueous suspension, prescription drug product nasal spray approved by the FDA for the treatment of symptoms associated with Seasonal Allergic Rhinitis. Each unit of Ryaltris™ nasal spray contains 665 mcg of olopatadine hydrochloride, a histamine-1(H1)-receptor inhibitor, and 25 mcg of mometasone furoate, a corticosteroid. The combination drug product nasal spray is indicated for the treatment of symptoms associated with seasonal allergic rhinitis in adults and pediatric patients 12 years of age and older. The safety and effectiveness of Ryaltris™ in pediatric patients younger than 12 years of age has not been established.

The recommended daily dose for Ryaltris is 2 sprays in each nostril twice daily.

Ryaltris will be marketed and distributed in the United States through their partner Hikma Specialty U.S.A. Inc., Columbus, OH.

Ryaltris has been approved and is marketed in Australia, the Czech Republic, Poland, Russia, South Africa, Ukraine, the United Kingdom, and Uzbekistan. In April 2021, Glenmark concluded the DCP regulatory procedure in Europe, enabling approval in 17 countries across EU and UK.

Glenmark has entered into commercial agreements with several partners around the world, including Menarini for the commercialization of Ryaltris™ in select EU markets, and with Bausch Health in Canada (where it is under review by Health Canada).

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

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

FDA Approves Ryaltris (mometasone and olopatadine) Nasal Spray for Seasonal Allergic Rhinitis

FDA Approves Cibinqo (abrocitinib) for Adults with Moderate-to-Severe Atopic Dermatitis

Pfizer Inc. (NYSE: PFE) announced  the United States (U.S.) Food and Drug Administration (FDA) approval of  Cibinqo (abrocitinib), an oral, once-daily, Janus kinase 1 (JAK1) inhibitor, for the treatment of adults living with refractory, moderate-to-severe atopic dermatitis (AD) whose disease is not adequately controlled with other systemic drug products, including biologics, or when use of those therapies is inadvisable.

Cibinqo is approved at the recommended doses of 100 mg and 200 mg, with the 200 mg dose being recommended for patients who are not responding to the 100 mg dose. Additionally, a 50 mg dose was approved to treat moderate-to-severe AD specifically in patients with moderate renal impairment (kidney failure), certain patients receiving treatment with inhibitors of cytochrome P450 (CYP) 2C19, or patients who are known or suspected to be poor metabolizers of CYP2C19. For patients with moderate renal impairment who are not responding to 50 mg once daily, 100 mg once daily may also be prescribed.

“The reality for patients living with chronic inflammatory skin disease such as moderate-to-severe atopic dermatitis is that many experience debilitating symptoms that are not managed by current treatment options. Today’s approval of Cibinqo will provide an important new oral option that could help those who have yet to find relief,” said Jonathan Silverberg, MD, PhD, MPH, Department of Dermatology, The George Washington University School of Medicine and Health Sciences. “In multiple large-scale clinical trials, Cibinqo demonstrated strong efficacy at clearing skin, improving itch, and managing the extent and severity of eczema, offering a benefit-risk profile that supports the use of this treatment in the FDA-approved patient population.”

The FDA approval was based on results of five clinical trials from a large-scale clinical trial program of more than 1,600 patients. The safety and efficacy of Cibinqo was evaluated in three randomized, placebo-controlled, Phase 3 trials. Additionally, safety was evaluated through a randomized, placebo-controlled, dose-ranging trial and an ongoing long-term open-label extension trial. Across the trials, Cibinqo demonstrated a consistent safety profile and profound improvements in skin clearance, extent of disease, and severity, as well as rapid improvement in itch after two weeks, for some people living with AD versus placebo. In addition, a higher proportion of subjects treated with Cibinqo in two monotherapy trials achieved improvement in itching at week 12 compared to placebo.

“The FDA’s approval offers hope to the millions of patients across the U.S. who are suffering daily with an immuno-inflammatory condition that can cause intense and persistent itching, pain, discomfort, and distress if left uncontrolled,” said Mike Gladstone, Global President of Pfizer Inflammation & Immunology. “Cibinqo, an efficacious once-daily pill, is a medical breakthrough made possible by Pfizer researchers and the people living with moderate-to-severe atopic dermatitis who participated in our clinical trials.”

“Atopic dermatitis is so much more than just a rash, and it goes beyond the surface of the skin. It’s a chronic condition that can both significantly disrupt patients’ daily lives and negatively impact their emotional well-being,” said Julie Block, President and CEO, National Eczema Association. “We appreciate Pfizer’s commitment to this resilient patient community and eagerly await the positive impact Cibinqo could have on the treatment landscape for moderate-to-severe atopic dermatitis.”

The most common adverse events reported in ≥5% of patients with Cibinqo included nasopharyngitis (12.4% with Cibinqo 100 mg, 8.7% with Cibinqo 200 mg, and 7.9%, with placebo), nausea (6%, 14.5%, and 2.1%, respectively), and headache (6%, 7.8%, and 3.5%, respectively).

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

https://www.clinicaltrials.gov/ct2/show/NCT04345367

FDA Approves Fleqsuvy (baclofen oral suspension) for the Treatment of Spasticity

Azurity Pharmaceuticals, Inc., a private specialty pharmaceutical company, focused on developing innovative products to meet the unique needs of patients with underserved conditions,  announced the U.S. Food and Drug Administration (FDA) approval of Fleqsuvy™ (baclofen oral suspension), 25 mg per 5 mL (5 mg/mL), Concentrated Formulation for the treatment of spasticity from multiple sclerosis (MS) or patients with spinal cord injuries and other spinal cord diseases.

“The approval of Fleqsuvy™ represents our commitment to providing innovative alternative formulations that address individualized patient needs. The clinical profile of Fleqsuvy™ allows for a tailored and flexible approach to dosing for patients suffering from spasticity, a debilitating symptom that may impact daily functioning,” said Amit Patel, Chairman and CEO of Azurity Pharmaceuticals.

Nearly 1 million people are living with Multiple Sclerosis in the United States.1 Spasticity is a commonly reported symptom for MS, with an estimated prevalence of spasticity of 67%.2 Due to the severity of spasticity resulting from multiple sclerosis or patients with spinal cord injuries and other spinal cord diseases, dosing becomes paramount to providing appropriate relief. Furthermore, dysphagia is commonly experienced, affecting approximately 43% of multiple sclerosis patients3 and 16-30% of patients with spinal cord injuries. Fleqsuvy™ provides an option as a baclofen oral liquid medication at an effective dose for patients who have trouble swallowing pills or prefer a liquid formulation. As the most concentrated FDA-approved oral liquid baclofen formulation, Fleqsuvy™ allows for the lowest volume to be prescribed for patients, which can be an important consideration for those suffering from dysphagia.

About Fleqsuvy™

Fleqsuvy™ is a grape-flavored oral suspension formulation of baclofen approved by the FDA for the treatment of spasticity resulting from multiple sclerosis, particularly for the relief of flexor spasms and concomitant pain, clonus, and muscular rigidity. It may also be of some value in patients with spinal cord injuries and other spinal cord diseases. Fleqsuvy™ contains 25 mg per 5 mL (5 mg/mL) and is supplied in bottles of either 120mL or 300mL. Limitations of Use: Fleqsuvy™ is not indicated in the treatment of skeletal muscle spasm resulting from rheumatic disorders.

FDA Approves Pyrukynd (mitapivat) as First Disease-Modifying Therapy for Hemolytic Anemia in Adults with Pyruvate Kinase Deficiency

Agios Pharmaceuticals, Inc. (NASDAQ: AGIO), a leader in the field of cellular metabolism pioneering therapies for genetically defined diseases, announced  the   U.S. Food and Drug Administration (FDA) approval of Pyrukynd  (mitapivat) in the U.S. for the treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency, a rare, debilitating, lifelong hemolytic anemia. Pyrukynd  is a first-in-class, oral PK activator and the first approved disease-modifying therapy for this disease.

“The successful ACTIVATE and ACTIVATE-T studies demonstrate the impact of mitapivat in significantly improving hemolysis and anemia in PK deficiency,” said Hanny Al-Samkari, M.D., hematologist and clinical investigator at the Mass General Cancer Center and Harvard Medical School, and an investigator in these pivotal Phase 3 studies. “The FDA approval of mitapivat, a targeted agent and first disease-modifying medication in PK deficiency, is an encouraging step forward for these patients that addresses a significant unmet need.”

“Pyrukynd® is the first approved therapy for PK deficiency and marks an important milestone for these patients, who may face tremendous challenges and debilitating symptoms throughout the course of this lifelong disease,” said Rachael Grace, M.D., MMSc, pediatric hematologist, director of hematology clinical research at Boston Children’s Hospital and an investigator in the Phase 2 DRIVE PK and Phase 3 ACTIVATE studies. “Partnering with Agios and the PK deficiency community to improve understanding of the natural history of this rare disease and bring a new medicine to patients has been an honor, and I look forward to additional collaboration in the future.”

“I am so grateful that Pyrukynd® has been approved for PK deficiency. As both patient and caregiver, I spent the majority of my life feeling alone in this disease and never thought I would see a medicine approved,” said Kim Hall, who was diagnosed with PK deficiency in 1969 and is the mother of two adult daughters living with PK deficiency. All three women participated in the Phase 3 Pyrukynd® PK deficiency clinical program. “The experience of being part of the clinical trials has been impactful because of the connections we have built with other patients, healthcare providers and Agios colleagues who understand PK deficiency and are actively working to improve patients’ lives.”

“For more than a decade, we have been pioneering the science of PK activation in order to bring Pyrukynd® to people with PK deficiency and provide them with the first medication approved specifically to address this rare, debilitating blood disorder,” said Jackie Fouse, Ph.D., chief executive officer at Agios. “We remain committed to partnering with patients, caregivers, advocates and healthcare providers to ensure that the impact of Pyrukynd® is maximized through robust support, education and access programs. These connections have fueled today’s tremendous milestone for the PK deficiency community. Each of us at Agios is dedicated to making a difference for people with PK deficiency, as well as to expanding the reach of Pyrukynd® and our clinical and research programs to many more patients with genetically defined diseases around the world.”

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

https://clinicaltrials.gov/ct2/show/NCT05031780

FDA Approves Norliqva (amlodipine) Oral Solution for Hypertension and Coronary Artery Disease

In continuation of my update on amlodipine besylate

The U.S. Food and Drug Administration has approved Norliqva (amlodipine) oral solution for the treatment of:

• Hypertension in adults and children 6 years and older, to lower blood pressure.
• Coronary artery disease [Chronic Stable Angina, Vasospastic Angina (Prinzmetal’s or Variant Angina) and Angiographically Documented Coronary Artery Disease in patients without heart failure or an ejection fraction <40%.]

• Amlodipine is a widely used long-acting calcium channel blocker first approved by the FDA thirty years ago. It is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure, and is thought to reduce the total peripheral resistance and inhibit coronary spasm to relieve angina.

  Amlodipine is FDA approved under the brand names Norvasc (amlodipine oral tablets) and Katerzia (amlodipine oral suspension), and the oral tablets are also available as generics.

  Norliqva is supplied as a peppermint flavored oral solution containing 1 mg/mL amlodipine as the besylate salt. It is administered once daily.

  Most common adverse reactions to amlodipine include edema, dizziness, flushing and palpitation which occurred in a dose related manner. Other adverse reactions not clearly dose-related but reported with an incidence >1.0% are fatigue and nausea.

https://www.webmd.com/drugs/2/drug-5891/amlodipine-oral/details

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

Spectrum Pharmaceuticals Submits New Drug Application for Poziotinib

Spectrum Pharmaceuticals, a biopharmaceutical company focused on novel and targeted oncology therapies, announced the submission of  its New Drug Application (NDA) for poziotinib to the U.S. Food and Drug Administration (FDA) for use in patients with previously treated locally advanced or metastatic non-small cell lung cancer (NSCLC) with HER2 exon 20 insertion mutations. The NDA submission is based on the positive results of Cohort 2 from the ZENITH20 clinical trial, which assessed the safety and efficacy of poziotinib. The product has received Fast Track designation and there is currently no treatment specifically approved by the FDA for this indication.

“The NDA submission for poziotinib marks an important step in achieving a first treatment for patients with HER2 exon 20 insertion mutations in lung cancer,” said Joe Turgeon, President and CEO of Spectrum Pharmaceuticals. “I want to thank the patients, investigators and our internal staff who have passionately worked to achieve this important milestone in an area of high unmet medical need.”

ZENITH20 Cohort 2 Clinical Results Summary

Results for Cohort 2 of the ZENITH20 clinical trial have been published in the Journal of Clinical Oncology (November 29, 2021), and can be accessed by clicking here.

Cohort 2 enrolled 90 patients who received an oral once daily dose of 16 mg of poziotinib. The intent-to-treat analysis demonstrated a confirmed objective response rate (ORR) of 27.8% (95% Confidence Interval (CI), 18.9%-38.2%). The observed lower bound of 18.9% exceeded the pre-specified lower bound of 17%. The median duration of response was 5.1 months and the median progression free survival was 5.5 months. In this cohort, 87% of patients had drug interruptions with 11 patients (12%) permanently discontinuing due to adverse events. 13 patients (14%) had treatment-related serious adverse events. As previously announced, the company had a successful pre-NDA meeting with the FDA which resulted in an agreement to submit an NDA for poziotinib. During the meeting, Spectrum confirmed with the FDA that Cohort 2 data could serve as the basis of an NDA submission. The company will continue to work with the FDA as appropriate, while the agency conducts its review.

More : https://investor.sppirx.com/news-releases/news-release-details/spectrum-pharmaceuticals-submits-new-drug-application-poziotinib

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

FDA Approves Leqvio (inclisiran), First-in-Class siRNA to Reduce Low-Density Lipoprotein Cholesterol (LDL-C)

Novartis  announced the US Food and Drug Administration (FDA) approval of Leqvio® (inclisiran), the first and only small interfering RNA (siRNA) therapy to lower low-density lipoprotein cholesterol (also known as bad cholesterol or LDL-C) with two doses a year, after an initial dose and one at three months.

"Leqvio is a revolutionary approach to lower LDL-C, and creates new possibilities for how healthcare systems can impact cardiovascular disease, a defining public health challenge of our time," said Vas Narasimhan, Novartis CEO. "We now have the opportunity, working together with partners, to provide this first-ever approved LDL-C–lowering siRNA-based therapy to tackle ASCVD at scale across the United States."

Leqvio is indicated in the United States as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with clinical atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) who require additional lowering of LDL-C. The effect of Leqvio on cardiovascular morbidity and mortality is being explored in clinical trials currently underway.

"ASCVD is a substantial public health burden affecting 30 million Americans," said Norman Lepor, MD, a Los Angeles based cardiologist and a clinical investigator in the Phase III clinical program for Leqvio. "As a first-of-its-kind siRNA therapy, Leqvio works differently than other cholesterol treatments, with twice-yearly dosing that makes it a compelling option for the millions of people with ASCVD already on cholesterol-lowering medications struggling to reach their LDL-C target."

Leqvio reduces the amount of LDL-C in the bloodstream by improving the liver's natural ability to prevent the production of a protein that plays a role in keeping circulating cholesterol levels high6,7. It is a subcutaneous injection given by a healthcare provider with an initial dose, then again at three months, and then every six months1. This approach may help those who have trouble sticking to medicines that are self-administered and have greater dosing frequency. Leqvio will be available in early January 2022.

"People with ASCVD have most likely experienced a heart attack or stroke from high cholesterol, causing a burden on the family and having a negative impact on lives," said Andrea Baer, Executive Director of The Mended Hearts, Inc. "One of the first steps to improving patients' health is to manage high cholesterol and we're encouraged that this new twice-a-year treatment offers a new option." 

The FDA approval was based on results from the comprehensive Phase III ORION-9, -10 and -11 clinical trials, in which all 3,457 participants with ASCVD or HeFH had elevated LDL-C while receiving a maximally tolerated dose of statin therapy2,3. In the Phase III trials at month 17, Leqvio delivered effective and sustained LDL-C reduction of up to 52% vs. placebo and was reported to be well-tolerated with a safety profile shown to be comparable to placebo2,3. The most common side effects were mild to moderate injection site reaction (including pain, redness and rash), joint pain, urinary tract infection, diarrhea, chest cold, pain in legs or arms and shortness of breath2,3.

Novartis has obtained global rights to develop, manufacture and commercialize Leqvio under a license and collaboration agreement with Alnylam Pharmaceuticals, a leader in RNAi therapeutics.

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

https://www.bachem.com/news/galnac-delivering-promise-of-oligonucleotides/