Samelisant Shows Promise in Treating Narcolepsy
A new drug, samelisant, could offer relief for individuals grappling with narcolepsy. Recent study findings suggest it considerably reduces excessive daytime sleepiness, paving the way for phase 3 trials.
Samelisant’s Impact on Excessive Daytime Sleepiness
A phase 2 study (NCT04072380) assessed samelisant,developed by Suven Life Sciences,as a monotherapy for narcolepsy patients. The results indicated that the treatment led too a notable betterment in excessive daytime sleepiness (EDS). These findings support further investigation in a phase 3 study, anticipated to commence this quarter.
The randomized, proof-of-concept study involved 190 patients diagnosed with narcolepsy adn EDS. Treatment with samelisant resulted in a statistically significant decrease in epworth Sleepiness Scale (ESS) scores over 14 days (P <.024). Compared to the placebo group,patients receiving samelisant experienced a clinically meaningful reduction of -2.1 points in their total ESS score.
The data were presented at both the 2025 SLEEP Annual Meeting in Seattle and the 2025 American Academy of Neurology (AAN) Annual Meeting. Led by Ramakrishna Nirogi, PhD, vice president of Suven Life sciences, the study also revealed improvements in EDS based on patient Global Impression-Severity (PGI-S) and PGI-Change scores. The therapy was generally safe and well-tolerated, with no serious adverse events or deaths reported, according to the study authors.
How Samelisant Works
Samelisant,an investigational agent,functions as a selective inverse agonist of histamine 3 receptors. This approach is gaining traction in narcolepsy treatment.By blocking H3 autoreceptors, which typically inhibit histamine release, these agents enhance histaminergic neurotransmission, promoting wakefulness without directly stimulating monoaminergic systems like customary stimulants.
Study Design and Key Findings
The phase 2 trial included patients aged 18 to 65 with narcolepsy, an ESS score of at least 12, and a mean Maintenance of Wakefulness test (MWT) time of less than 12 minutes. Participants were randomly assigned to receive either samelisant 2 mg, samelisant 4 mg, or a placebo for 14 days. Secondary endpoints included changes in CGI-S, CGI-C, and PGI-C scores related to EDS, as well as changes in MWT scores.
Also known as SUVN-G3031, samelisant has been explored as a potential treatment for Parkinson’s disease (PD) patients experiencing EDS. Preclinical models, presented at SLEEP 2023, showed that samelisant increased wake time in hemiparkinsonian rats. Specifically,post-samelisant treatment (10 and 30 mg/kg,orally) significantly increased cumulative wake time in the first 3 hours.
According to the Parkinson’s Foundation, about half of people with Parkinson’s experience excessive daytime sleepiness (Parkinson’s Foundation).
Earlier Studies and Safety Profile
A phase 1 study published in Clinical Drug Investigation (2020) assessed samelisant in healthy volunteers, demonstrating its safety and tolerability at single doses up to 20 mg and multiple doses up to 6 mg onc daily. The study found that steady state was achieved by day 6 with once-daily dosing,and renal excretion of unchanged samelisant was the primary route of elimination.
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