104 of 119 adults with hypersomnia had treatment-emergent adverse events on pitolisant

Treatment-emergent adverse events were reported for 104 of 119 adults with idiopathic hypersomnia receiving pitolisant, the study record from Harmony Biosciences Management, Inc. shows. Long-term safety data and sleepiness scores are now available for participants who completed the preceding double-blind randomized withdrawal study.

Why it matters

WAKIX, the pitolisant product, is indicated for excessive daytime sleepiness or cataplexy in patients 6 years of age and older with narcolepsy, according to the prescribing information published Feb 26, 2026. The long-term study addressed a different population: adults with idiopathic hypersomnia who had completed the double-blind randomized withdrawal phase of HBS-101-CL-010. Its stated objective was to assess long-term safety and effectiveness in those participants, the study record says.

Treatment-emergent adverse events

Results were first posted November 13, 2026. The completed Phase 3 study assessed treatment-emergent adverse events over approximately 3 years, the record shows.

A treatment-emergent adverse event was any new adverse event or worsening of a pre-existing condition reported after the first dose of study drug and up to 30 days after the date of the last dose. The safety population included participants who enrolled and took at least 1 dose of pitolisant. All 119 participants received study treatment; 104 had at least one treatment-emergent adverse event, according to the record.

The separate adverse-event tables list serious adverse events in 6 of 119 participants and no deaths. The record lists headache in 14 participants, insomnia in 16 and nausea in 8. These are counts of participants with the listed conditions, according to the study record.

Epworth Sleepiness Scale scores

Change from baseline in Epworth Sleepiness Scale (ESS) score was another primary outcome. The scale ranges from 0 to 24, with higher scores representing more severe daytime sleepiness, the record says.

The reported mean changes and standard deviations were:

Week 4: -3.7, standard deviation 4.53, among 119 participants.
Month 7: -3.1, standard deviation 5.13, among 100 participants.
Month 13: -3.4, standard deviation 4.74, among 88 participants.
Month 19: -3.0, standard deviation 5.83, among 70 participants.
Month 25: -4.0, standard deviation 5.50, among 42 participants.
Month 31: -3.3, standard deviation 3.44, among 6 participants.

The number analyzed at each visit was the number of participants evaluable at that time, according to the record. These results describe changes within the pitolisant group; the study design lists a single group with no masking.

Participants and dosing

Before enrollment, participants had received open-label pitolisant and then been randomized to pitolisant or placebo in HBS-101-CL-010, NCT05156047, the record says. Eligibility for the long-term study required completion of that withdrawal phase and continued eligibility under the long-term protocol.

Participants took pitolisant once daily in the morning upon wakening. The protocol described a titration period with a maximum dose of 35.6 mg, based on the investigator's assessment of safety, tolerability and effectiveness. During long-term dosing, the protocol allowed dose adjustments in increments of 4.45 mg, from 8.9 mg up to 35.6 mg, the record says.

The mean age was 40.1 years; 95 participants were female and 24 were male. The participant-flow table lists 62 who completed the study and 57 who did not. Reasons for not completing included lack of efficacy for 13 participants, an adverse event for 6 and loss to follow-up for 7, according to the record.