Smith-Magenis Syndrome

The FDA flashed a red light on Vanda Pharmaceuticals’ experimental treatment for a gastrointestinal condition that disrupts the digestion process. The agency rejected tradipitant in gastroparesis on Wednesday, the Washington-based company said Thursday morning. The biotech said it will keep seeking approval and will still support the expanded access program for the “several dozen patients” currently using that pathway. Vanda offered a stinging rebuke of the agency’s actions, complaining that the FDA’s decision was delayed by more than 185 days and failed to “satisfy the requirements specified by the Food Drug and Cosmetic Act (FDCA).” The company was also miffed that the regulator didn’t grant an advisory committee hearing, which Vanda wanted. The company submitted two placebo-controlled studies of part of its application package. Signs did not seem to be pointing in Vanda’s favor after the company said in its second-quarter earnings update that “deficiencies” precluded the regulator from having discussions with Vanda about the drug’s label. The FDA told the company that its response then should not be considered a teaser of a decision on the full application. “If you see it from the patient need, I think it is very important that tradipitant makes it to the armamentarium of drugs for gastroparesis,” CEO Mihael Polymeropoulos said. There has been “no effective treatment approved by the FDA in over 40 years” for the condition, the company added. The latest rejection follows the FDA’s decision earlier this year not to tack on insomnia to the label of Vanda’s Hetlioz. The drug is approved to treat non-24-hour sleep-wake disorder and a rare behavioral condition called Smith-Magenis syndrome, but the FDA was dissatisfied by the package informing the insomnia ask. Patients treated with tradipitant have filed a citizen petition with the FDA, requesting the agency approve it for gastroparesis, Vanda said Thursday. The company added it will also submit a different NDA for the drug for vomiting prevention in motion sickness by year’s end. Vanda’s stock price $VNDA dropped about 12% before the opening bell.

TEL-AVIV, Israel, July 30, 2024 /PRNewswire/ -- Neurim Pharmaceuticals ("Neurim") announces that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion, recommending an extension to the existing indication to include the treatment of Insomnia in children with Neurogenetic disorders (NGDs). Slenyto® is a child appropriate prolonged release melatonin formulation that was approved in the EU in 2018 for the treatment of insomnia in children with autism spectrum disorder (ASD) and/ or Smith-Magenis Syndrome. Slenyto® is the only authorised medication for insomnia in these disorders. The adopted recommended wording for the extended indication is: "Slenyto® is indicated for the treatment of insomnia in children and adolescents aged 2-18 with autism spectrum disorder (ASD) and/or neurogenetic disorders with aberrant diurnal melatonin secretion and /or nocturnal awakenings, where sleep hygiene measures have been insufficient". "The positive CHMP opinion on Slenyto® represents a significant milestone in addressing an unmet need for children with NGDs, who suffer severely from impaired sleep. Upon approval, Slenyto® would be the only medicinal product approved for sleep disorders in this unique paediatric population, allowing treatment initiation at an early age," said Prof. Nava Zisapel, CEO of Neurim Pharmaceuticals. Paul Gringras, Professor of paediatric Sleep Medicine, London, England commented: "Melatonin deficiency or misalignment is a common pathophysiological mechanism for insomnia in neurogenetic disorders. Slenyto® is a prolonged-release formulation of melatonin that delivers melatonin over the course of the night, mimicking the endogenous release profile in healthy subjects. Therefore, Slenyto® has the potential to treat the pathophysiology of insomnia in this population improving sleep latency, sleep continuity and total nighttime sleep duration. Slenyto® has been specifically formulated for use in children and has a favorable safety profile. The treatment will address a significant need in the medical management of many children and adolescents with NGDs". ABOUT INSOMNIA IN CHILDREN WITH NEUROGENETIC DISORDERS (NGDs) Sleep impairment is a common comorbidity in neurogenetic disorders, with up to 86% of children reported to experience disrupted sleep, starting at an early age. During early childhood, sleep plays an essential role in healthy cognitive and psychosocial brain development, influencing learning memory, emotional regulation, and brain structure. Children with neurogenetic disorders tend to develop insomnia and other sleep disorders at an early age. Insomnia has a significant impact on these children, aggravating disease symptoms and reducing quality of life in both patients and caregivers. Current practices recommend parent-directed behavioral sleep interventions as first-line treatment for pediatric insomnia in NGDs, with a 25% response rate. Slenyto® will be the first approved pharmacological treatment for insomnia in children and adolescents with NGDs. ABOUT SLENYTO ® Slenyto® is an age-appropriate prolonged-release formulation of melatonin, a hormone involved in the regulation of circadian clock and sleep. The mini-tablet innovative formulation was specifically designed to facilitate ease of swallowing without resistance in pediatric ASD and NGD population, in response to the unmet medical need in the field of paediatric insomnia. Slenyto® delivers melatonin over the night to mimic the endogenous melatonin release profile in healthy subjects. In a Phase III study in ASD and SMS children and adolescents, Slenyto® improved sleep latency, sleep continuity and total nighttime sleep duration. The positive effect on sleep maintenance and duration was associated with an improvement in externalizing behavior, which correlated with an improvement in parents' well-being. The mechanism of action of Slenyto® on sleep latency, sleep maintenance and total sleep time is independent of the background disorder. Therefore, any patient with a neurogenetic disorder with sleep disturbances associated with aberrant diurnal melatonin secretion patterns and/or insufficient nighttime melatonin secretion will benefit from Slenyto®. ABOUT NEURIM PHARMACEUTICALS Neurim Pharmaceuticals Ltd. () is a neuroscience drug discovery and development company. Its first approved drug, CIRCADIN®, is approved for patients over the age of 55 who are suffering from insomnia and is commercially available in 45 countries around the world, including Europe, Asia-Pacific, Latin America, Africa and the Middle East. Neurim has a strong and innovative product pipeline targeting central nervous system (CNS) disorders. Contact: Guy Manor VP Commercial Operations [email protected]

The FDA cleared Vanda Pharmaceuticals’ Fanapt (iloperidone) for the acute treatment of manic or mixed episodes associated with bipolar I disorder in adults, marking the oral atypical antipsychotic’s second US approval following authorisation for schizophrenia in 2009."Manic or mixed episodes associated with bipolar I disorder are highly complex conditions, which require a host of trusted options to meet individual patient needs,” said Vanda CEO Mihael Polymeropoulos, adding that Fanapt is a “therapeutic agent that offers flexible dosing with a well-known safety profile.”  The expanded label approval was based on findings from a Phase III study, in which 400 participants with bipolar I disorder experiencing a current episode of mania were randomly assigned to either Fanapt or placebo. At the four-week assessment, Fanapt demonstrated a significantly greater improvement than placebo on the primary endpoint of mania severity, as measured by the Young Mania Rating Scale (YMRS). Moreover, clinical benefits were evident in the Fanapt group as early as week two.Vanda noted that Fanapt’s safety profile was consistent with its previous studies in schizophrenia. The drug’s label carries a boxed warning highlighting an increased risk of death in elderly patients with dementia-related psychosis.Within its neuropsychiatric portfolio, Vanda is also looking to broaden the label for Hetlioz (tasimelteon), which was approved for non-24-hour sleep-wake disorder in 2014 and nighttime sleep disturbances associated with Smith-Magenis Syndrome in 2020. However, the melatonin receptor agonist was slapped with a complete response letter by the FDA for its label expansion in jet lag disorder in 2019 and more recently in insomnia.