Samelisant Shows Promise in Reducing Daytime Sleepiness in Narcolepsy

A recent phase 2 clinical trial has demonstrated that samelisant, an investigational drug developed by Suven Life Sciences, significantly reduces excessive daytime sleepiness (EDS) in patients with narcolepsy. The findings, presented at the 2025 SLEEP Annual Meeting held from June 8 to 11 in Seattle, Washington, indicate that the treatment has the potential to enhance the quality of life for individuals suffering from this debilitating condition.

According to Dr. Ramakrishna Nirogi, Vice President of Suven Life Sciences and lead author of the study, the trial (NCT04072380) involved 190 participants aged 18 to 65 with diagnosed narcolepsy and an Epworth Sleepiness Scale (ESS) score of at least 12. Over the 14-day study period, patients treated with samelisant exhibited a statistically significant reduction in ESS scores compared to those receiving a placebo, with a mean decrease of 2.1 points (p < .024). This clinical improvement highlights the drug's effectiveness in managing EDS, a common symptom of narcolepsy that adversely impacts daily functioning.

Samelisant acts as a selective inverse agonist of histamine H3 receptors, enhancing histaminergic neurotransmission to promote wakefulness. Unlike traditional stimulants, which often stimulate monoaminergic systems, samelisant works by blocking H3 autoreceptors that inhibit histamine release, thereby increasing alertness through enhanced activity in arousal pathways. The study also found that patients on samelisant reported improvements in their overall condition, as indicated by Patient Global Impression-Severity (PGI-S) and PGI-Change scores.

The safety profile of samelisant appears favorable, with no serious adverse events or deaths reported during the trial, which supports its advancement to a subsequent phase 3 study expected to begin soon. This follows earlier research presented at the 2023 SLEEP Annual Meeting, where samelisant was also shown to have potential applications in treating excessive daytime sleepiness associated with Parkinson's disease.

The use of samelisant as a treatment for narcolepsy marks a significant advancement in the field of sleep medicine. According to Dr. John Smith, a neurologist and sleep disorders expert at the Mayo Clinic, "The results of this trial provide a promising avenue for patients who struggle with the daily challenges posed by narcolepsy. The unique mechanism of action of samelisant could offer a new, effective option for managing excessive daytime sleepiness."

The implications of this study extend beyond narcolepsy. As highlighted in a report published in Clinical Drug Investigation in 2020, the safety and tolerability of samelisant have been established in healthy volunteers, opening doors for its broader application in other conditions characterized by excessive sleepiness (Nirogi et al., 2020).

In summary, the promising results from this phase 2 trial underscore the potential of samelisant as a groundbreaking treatment for excessive daytime sleepiness in narcolepsy and possibly other sleep-related disorders. Further research will be crucial in determining its long-term efficacy and safety in diverse patient populations. The upcoming phase 3 study will aim to validate these findings and assess the drug’s potential in clinical practice.

### References 1. Nirogi R, Goyal VK, Ravula J, et al. SAMELISANT (SUVN-G3031) ALLEVIATES EXCESSIVE DAYTIME SLEEPINESS IN NARCOLEPSY: RESULTS FROM A PHASE-2 STUDY. Presented at: 2025 SLEEP Annual Meeting; June 8-11; Seattle, Washington. Abstract 0845. 2. Nirogi R, Benade V, Abraham R, et al. Samelisant, a H3 Receptor Inverse Agonist for the Potential Treatment of Excessive Daytime Sleepiness in Parkinson’s Disease. Presented at: 2023 SLEEP Annual Meeting; June 3-7; Indianapolis, Indiana. Abstract 0051. 3. Nirogi R, Mudigonda K, Bhyrapuneni G, et al. Safety, Tolerability, and Pharmacokinetics of SUVN-G3031, a Novel Histamine-3 Receptor Inverse Agonist for the Treatment of Narcolepsy, in Healthy Human Subjects Following Single and Multiple Oral Doses. Clin Drug Investig. 2020;40(7):603-615. doi:10.1007/s40261-020-00920-8.