Long-Term Evaluation of Safety and Efficacy of Pitolisant in Narcolepsy: HARMONY 3 Study (S46.009)

Objective: To evaluate the long-term safety and efficacy of pitolisant. Background: HARMONY 3 is a long-term (up to 5 years) study of pitolisant, the first potent and highly selective histamine 3 (H3)-receptor antagonist/inverse agonist, in patients with narcolepsy. Design/Methods: This pragmatic, open-label, multicenter study evaluated the effect of pitolisant (18 or 36 mg once daily) in adult patients with narcolepsy (with or without cataplexy) according to ICSD-2 criteria with excessive daytime sleepiness (EDS; Epworth Sleepiness Scale [ESS] score ≥12). Concomitant use of stimulants and anticataplectic agents was permitted. The 1-year results are presented here. Results: Of 102 patients who received study drug, 73 were not previously treated (de novo) with pitolisant; 29 were previously treated (compassionate use program [n=16], another pitolisant trial [n=13]). Mean age was 36 years; 44.1% were male. At baseline, mean ESS was 17.1 ± 3.1; 73.5% of patients had cataplexy. Sixty-eight patients completed ≥12 months of treatment. Mean pitolisant exposure was 260 and 548 days for de novo and previously treated patients, respectively; 72% of patients received pitolisant 36 mg/d. During this 12-month period, 56.9% of patients reported adverse events: headaches (11.8%), insomnia (8.8%), weight gain (7.8%), anxiety (6.9%), depression (4.9%), and nausea (9%). Mean ESS reduction was 4.3 points overall; 4.9 (P Conclusions: This 1-year analysis of a long-term, open-label study supported the safety and efficacy of pitolisant for the treatment of EDS in narcolepsy and cataplexy in narcolepsy. Disclosure: Dr. Dauvilliers has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Bioprojet, Flamel Technologies S.A. (now Avadel Pharmaceuticals plc), Harmony Biosciences, LLC, Idorsia Pharmaceuticals Ltd., Jazz Pharmaceuticals, Takeda Pharmaceutical Co. Ltd., Theranexus, and UCB Pharma. Dr. Arnulf has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Bioprojet, Novartis, UCB Pharm. Dr. Szakacs has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Bioprojet. Dr. Scart-Gres has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Bioprojet. Dr. Lecomte has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Bioprojet. Dr. Causse has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Bioprojet. Dr. Schwartz has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Bioprojet Pharma.