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.”