Smith-Magenis Syndrome

iStock, photoguns Vanda is criticizing the FDA’s restrictions on information companies can provide regarding off-label use of approved medicines. Despite suffering a series of rebuffs from the FDA, Vanda Pharmaceuticals is continuing to fight for sedative Hetlioz, suing the regulator last week to use the drug off-label for jet lag. In the complaint, filed April 9 with the U.S. District Court for the Southern District of Texas, Vanda slammed the regulator’s “restrictive regulatory regime,” and alleged a violation of the company’s First Amendment right to provide doctors with relevant information about its drugs, as per reporting from Fierce Pharma . Hetlioz is a sedative that was first approved in 2014 for non-24-hour sleep-wake disorder and was later granted a label expansion to cover sleep disorders for the rare disease Smith-Magenis syndrome. At issue is Vanda’s desire to promote Hetlioz in off-label uses. Doctors can legally prescribe approved drugs off label for uses that have yet to be cleared by the FDA, but the agency limits the information that companies can share about unapproved uses. As per a recent guidance document , drug sponsors “should provide and appropriately present all information necessary” to allow healthcare providers to better assess the benefits and risks of the unapproved uses. Companies should also be “truthful and non-misleading,” according to the FDA guidance. Their communications to doctors should emphasize that the product has not yet been approved by the FDA for the use and include details regarding known contraindications and safety risks. Vanda took issue with these restrictions, noting in its press release that they “prevent pharmaceutical manufacturers from sharing their new discoveries with doctors” for fear of being misleading, Fierce reported. The biotech added that while they have a “credible fear” of being sanctioned for sharing Hetlioz data to doctors, it’s the patients who “ultimately suffer” from the FDA’s limitations. Also in the court complaint, Vanda provided detailed clinical information about Hetlioz’s efficacy and safety in patients with jet lag, for which the drug is not approved. Vanda insists that the data support the drug’s use in this indication. The biotech is asking the court to declare its information about off-label Hetlioz use to be truthful. Vanda’s latest lawsuit puts even more pressure on an already-strained relationship with the FDA. In July 2019, the regulator rejected Vanda’s bid for approval of Hetlioz in jetlag, a decision which the biotech appealed. Vanda asked for a hearing on the verdict in July 2022, but after months of not hearing back, the biotech sued the regulator for not being able to stick to its mandated timeline. The FDA last year also rejected Vanda’s application for the NK-1R antagonist tradipitant for gastroparesis, a move that the biotech again contested. In September 2024, Vanda argued that the regulator’s verdict “generally disregarded the evidence provided.” The biotech again blasted the FDA’s timeline—the decision on tradipitant was delayed by more than 185 days, which violates the Federal Drug and Cosmetic Act’s 180-day deadline, Vanda argued. In January, the biotech escalated the matter to then-FDA Commissioner Robert Califf. In a letter, Vanda called attention to the “culture of obfuscation and closemindedness” at the agency, which it faults for the lack of transparency regarding tradipitant’s rejection. A few days after the letter, the FDA finally provided Vanda with a justification for the rejection and gave the company the chance to request a hearing.

The April 9 complaint, filed in federal district court in Texas on behalf of Vanda, a doctor and a frequent flier, disputes the “chilling effect” of the FDA’s “restrictive regulatory regime.” After years of back-and-forth with the FDA over Hetlioz's potential use as a jet lag disorder treatment, Vanda Pharmaceuticals is pursuing a new route to establish the drug in the space.Hetlioz was approved more than a decade ago for non-24-hour sleep-wake disorder, a circadian rhythm condition, and expanded its label in 2020 to target nighttime sleep disorders associated with the rare neurodevelopmental disorder Smith-Magenis syndrome.In 2019, the FDA issued a complete response letter regarding Vanda’s application to expand Hetlioz's label to include people experiencing sleep issues from jet lag.Following an unsuccessful attempt to dispute the snub, Vanda requested a hearing on the application in 2022; a few months later, when that process had failed to advance, the company sued the FDA over its alleged failure to abide by required timelines.The dispute came to a head in the spring of 2024 with the FDA’s official rejection of both the hearing request and the supplemental application for Hetlioz.An FDA rejection is typically the end of the road for most drugmakers, at least until they resubmit a filing, but Vanda is treating it as more of a speed bump. The pharma this week filed suit against the agency once again, this time protesting the rules around promoting drugs’ off-label uses.Though doctors are legally allowed to prescribe medications for uses other than those listed on their FDA-approved labels, companies are restricted in the information they can share with healthcare providers and patients about unapproved uses.The April 9 complaint, filed in federal district court in Texas on behalf of Vanda, a doctor and a frequent flier, disputes the “chilling effect” of the FDA’s “restrictive regulatory regime” that allegedly violates Vanda’s right under the First Amendment of the U.S. Constitution to communicate information about its product’s uses, approved or otherwise. Drugmakers are largely barred from promoting unapproved uses of their approved drugs, and, as Vanda noted in the filing, the FDA has frequently taken legal action against companies that engage in what it deems “misbranding.” There is, however, some leeway when it comes to sharing scientific information about off-label usage.A recently finalized guidance document (PDF) from the FDA offers recommendations for firms looking to share such information with healthcare providers. Among other stipulations, the information should be “truthful and non-misleading” as well as “scientifically sound,” according to the document. Further, the communications should be accompanied by information about the FDA-approved labeling and a statement “that the unapproved use(s) of the medical product has not been approved by FDA and that the safety and effectiveness of the medical product for the unapproved use(s) has not been established,” the guidance doc explains.Overall, per the FDA, scientific information that companies provide about off-label drug use can’t be seen in any way as encouraging or persuading doctors of the benefits of such usage; it should merely offer them objective information that they can then use to “make their own clinical decisions.”In its lawsuit, Vanda said it maintains a “credible fear” of being prosecuted for sharing clinical efficacy data about Hetlioz’s use in treating jet lag disorder—even if that information is accurate. The company also refuses to “contradict the extensive evidence confirming the safety and efficacy of Hetlioz” with the FDA's suggested disclaimer.“Because FDA’s regulations prevent pharmaceutical manufacturers from sharing their new discoveries with doctors and condition speech on an obligation to mislead doctors about the safety and efficacy of their products, patients ultimately suffer,” the plaintiffs wrote. Vanda said it contacted the FDA in 2022 detailing certain information it wished to share about off-label use of Hetlioz and received only a “vague response” stating that the proposal “raised some concerns” for the FDA, with no further follow-up. The company said this feedback confirmed its fear of prosecution if it were to share the materials.The 63-page complaint details the clinical data that Vanda would like to share, which it says demonstrates Hetlioz’s ability to improve sleep in people with jet lag disorder, plus mockups of various cover sheets for the data. The filing also veers at one point into a re-litigation of Vanda’s application for approval in the indication, calling the FDA’s reasons for rejection “mistaken in multiple ways” and proceeding to dispute several aspects of the decision.Vanda concludes by asking the court to confirm that the statements it wants to make about off-label use of Hetlioz are truthful and non-misleading, and to uphold the First Amendment rights of both the company and the public to make and receive such statements.In response to a request from Fierce Pharma Marketing, a spokesperson for the FDA’s parent agency said the Department of Health and Human Services “does not comment on ongoing litigation.”Editor's note: This story was updated with a response from the HHS.

TEL AVIV, Israel, March 26, 2025 /PRNewswire/ -- Neurim Pharmaceuticals ("Neurim") announces that the European Commission has approved the extension of the indication to include the treatment of insomnia in children with attention deficit hyperactivity disorder (ADHD). The European Commission decision followed the recommendation of the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) in January 2025. Slenyto® is a child-appropriate prolonged release melatonin formulation that was first approved in the EU in 2018 for the treatment of insomnia in children with autism spectrum disorder (ASD) and/ or Smith-Magenis Syndrome. In 2024, the indication was extended to neurogenetic disorders (NGDs). Slenyto® is the only authorised medication for insomnia in these disorders. The adopted wording for the newly 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 In children and adolescents aged 6-17 years with attention-deficit hyperactivity disorder (ADHD) where sleep hygiene measures have been insufficient "We recognise there is significant unmet need and high demand for addressing sleep maintenance and duration as well as sleep initiation difficulties of children with ADHD, who suffer from impaired sleep. The European Commission (EC) granted marketing authorization (MA) of Slenyto® for insomnia in children with ADHD is a major move to satisfy this need." says Prof. Nava Zisapel, CEO of Neurim Pharmaceuticals. Prof. Carmen Schroder, MD, PhD, France, and Prof. Oliviero Bruni, MD, PhD, Italy, comment: " 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 the population of children with neurodevelopmental disorders, among which ADHD, improving sleep latency, sleep continuity and total nighttime sleep duration, in particular in those who do not produce sufficient endogenous melatonin. Slenyto® has been specifically formulated for use in children and has a favorable safety profile. Subsequent improvements in child behavior (mainly due to longer uninterrupted sleep), parent satisfaction and quality of life (mainly affected by the child's behavior) are expected. The treatment will address a significant need in the medical management of many children and adolescents with ADHD". ATTENTION DEFICIT HYPERACTIVITY DISORDER (ADHD) Sleep impairment is a common comorbidity in ADHD, with up to 70% of children reported to experience disrupted sleep, starting at an early age. Sleep duration and the number of nighttime awakenings in children with ADHD differ from those of typically developing children from a very young age – often before formal ADHD diagnosis. Co-occurring sleep problems in children with ADHD have been shown to predict more severe core symptoms, exacerbate daytime sleepiness, and reduce quality of life in both patients and caregivers. Current practices recommend parent-directed behavioral sleep interventions as first-line treatment for pediatric insomnia in ADHD. Slenyto® is a unique pharmacological treatment for insomnia in children and adolescents with ADHD that would address not only sleep initiation but also sleep maintenance and sleep duration disorders. ABOUT SLENYTO ® Slenyto® is an age-appropriate prolonged-release formulation of melatonin, a hormone involved in the regulation of the circadian clock and sleep. The mini-tablet's innovative formulation was specifically designed to facilitate ease of swallowing without resistance in pediatric ASD, NGD and ADHD populations, in response to the unmet need in the field of paediatric insomnia. Slenyto® delivers melatonin over the night to mimic the endogenous melatonin release profile in healthy subjects. In Phase III study in ASD and SMS children and adolescents, with and without ADHD, 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 improvement in parents' well-being. Analysis of Slenyto effect on the primary endpoint, total sleep time, demonstrated the same level of improvement in participants with and without ADHD comorbidity. 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 neurodevelopmental 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. Neurim has a strong and innovative product pipeline targeting central nervous system (CNS) disorders. Contact: Guy Manor, VP Commercial Operations, [email protected] WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED