Pitolisant Showed Sustained Benefit in Adults With Idiopathic Hypersomnia in New Phase 3 Trial

Long-term treatment with pitolisant was generally safe and well tolerated and was associated with sustained symptom improvement in adults with idiopathic hypersomnia (IH), according to final results from an open-label phase 3 trial presented at SLEEP 2026 in Baltimore, Maryland.

The study included 119 adults with IH who had completed the placebo-controlled, randomized withdrawal phase 3 INTUNE study. Participants received once-daily pitolisant at doses ranging from 8.9 mg to 35.6 mg for up to approximately 3 years, with data available through January 2026.

Pitolisant exposure was substantial in the long-term analysis. Median duration of treatment was 97.0 weeks, with a range of 3.0 to 151.0 weeks, and 65.8% of patients titrated to the maximum dose of 35.6 mg. Overall, 62 patients, or 52.1%, completed the study. The mean patient age was 40.1 years, and 79.8% of participants were female.

What safety findings were reported with long-term pitolisant?

Treatment-related treatment-emergent adverse events were reported in 30 patients, or 25.2% of the cohort. The most frequent treatment-related adverse events were insomnia (6.7%), headache (5.9%), dizziness (2.5%), and weight increase (2.5%).

Serious adverse events were reported in 6 patients, but none were considered treatment-related, according to the abstract. Investigators concluded that the safety and tolerability profile observed in adults with IH was consistent with the established safety profile of pitolisant in patients with narcolepsy.

Did pitolisant improve symptoms of idiopathic hypersomnia?

Effectiveness measures improved from baseline to week 4 and remained stable through month 25. Investigators evaluated multiple patient- and clinician-reported outcomes, including the Epworth Sleepiness Scale (ESS), Idiopathic Hypersomnia Severity Scale (IHSS), PROMIS Sleep Related Impairment-8a T-score, Sleep Inertia Questionnaire, Functional Outcomes of Sleep Questionnaire short version, Patient Global Impression of Severity of excessive daytime sleepiness, and Clinician Global Impression of Severity of IH.

At baseline, mean ESS score was 11.4, mean IHSS score was 27.9, mean PROMIS Sleep Related Impairment T-score was 59.5, mean Sleep Inertia Questionnaire score was 59.2, and mean FOSQ-10 score was 13.0. Across follow-up timepoints, mean changes from baseline ranged from –3.0 to –4.0 on ESS, –5.7 to –6.4 on IHSS, –3.8 to –5.2 on PROMIS Sleep Related Impairment, and +1.7 to +2.4 on FOSQ-10.

Why are these findings clinically relevant?

IH is a chronic neurologic sleep-wake disorder associated with excessive daytime sleepiness and sleep inertia. For primary care clinicians, the condition may be difficult to distinguish from more common causes of fatigue or sleepiness, including insufficient sleep, depression, medication effects, obstructive sleep apnea, and other medical or psychiatric conditions.

The current findings suggest that long-term pitolisant treatment may provide sustained improvement across several domains relevant to daily functioning, including daytime sleepiness, IH severity, sleep-related impairment, sleep inertia, and functional outcomes. However, the study was open label and included patients who had already completed the prior INTUNE trial, which should be considered when interpreting effectiveness and completion data.

Investigators concluded that pitolisant showed clinically meaningful and sustained improvements in multiple IH symptoms across more than 2 years of dosing.

Reference

1. Plante DT, Corser B, Drake C, et al. Long-term safety and effectiveness of pitolisant in adult patients with idiopathic hypersomnia: final results from an open-label phase 3 trial. Late-breaking abstract. Presented at: SLEEP 2026; June 2026; Baltimore, MD.