The safety and tolerability of pitolisant in the treatment of excessive daytime sleepiness and cataplexy in adult patients with narcolepsy: an open-label, expanded access program in The United States

Pitolisant Expanded Access Clinical Evaluation (PEACE) provides adult patients with narcolepsy access to treatment with pitolisant (an investigational medication in the United States). Enrolled patients are titrated to pitolisant 35.6 mg/day (or the highest tolerable dose) over a 3-week period. Dose adjustments are permitted at the discretion of the treating physician based on patient response with regard to efficacy and/or tolerability. Treating physicians follow their standard-of-care and are required to report adverse events and the use of concomitant narcolepsy medications. Results from an interim data collection are presented here. As of October 2018, 208 patients were enrolled: 63.0% female, 74.5% white, mean age of 40.3 years, and 59.1% with narcolepsy type 1. Nearly all patients (98.1%) had been previously treated with other narcolepsy medications (87.5% with ≥2 narcolepsy medications) prior to starting pitolisant. Most patients (91.1%) were titrated to the maximum dose of pitolisant (35.6 mg/d). To date, 149 patients have completed ≥1 month, 65 have completed ≥3 months, and 3 have completed ≥6 months of treatment. Most patients (60.1%) are on treatment with ≥1 concomitant narcolepsy medication, including traditional stimulants (51.9%), sodium oxybate (31.3%), modafinil (14.4%), armodafinil (12.5%), and antidepressants (3.8%). Overall, 8.2% of patients have discontinued from the program, 5.3% due to an adverse event (AE) and 1.1% for lack of effect. The most commonly reported AEs were headache (8.1% of patients), anxiety (3.8%), and nausea (3.4%). Adverse events were generally mild or moderate in intensity (99/103 AEs), and often occurred early in treatment. In the PEACE program, patient characteristics have been generally reflective of the US narcolepsy patient population. Most patients are receiving the optimal dose of pitolisant (35.6 mg once daily). Thus far, the safety/tolerability profile of pitolisant is consistent with that observed in the clinical development program and the postmarketing setting in Europe, with no new safety signals identified. Bioprojet Pharma and Harmony Biosciences, LLC.