Craig W Davis1, Ulf Kallweit2, Jean-Charles Schwartz3, Lois E Krahn4, Ben Vaughn5, Michael J Thorpy6. 1. Harmony Biosciences, LLC, Plymouth Meeting, PA, USA. Electronic address: cdavis@harmonybiosciences.com. 2. Universität Witten/Herdecke, Witten, Germany. 3. Bioprojet Pharma, Paris, France. 4. Mayo Clinic Hospital, Phoenix, AZ, USA. 5. Rho, Durham, NC, USA. 6. Albert Einstein College of Medicine, Bronx, NY, USA.
Abstract
STUDY OBJECTIVE: To evaluate the efficacy of pitolisant, a histamine 3 (H3)-receptor antagonist/inverse agonist, in adult patients with high burden of narcolepsy symptoms. METHODS: Data were pooled from two randomized, placebo-controlled, 7- or 8-week studies of pitolisant (titrated to a potential maximum dose of 35.6 mg/day) in adults with narcolepsy. Analyses included three independent patient subgroups: Epworth Sleepiness Scale (ESS) baseline score ≥16, Maintenance of Wakefulness Test (MWT) sleep latency ≤8 min, and ≥15 cataplexy attacks per week. RESULTS: The analysis populations included 118 patients for ESS (pitolisant, n = 60; placebo, n = 58), 105 for MWT (pitolisant, n = 59; placebo, n = 46), and 31 for cataplexy (pitolisant, n = 20; placebo, n = 11). On the ESS, least-squares mean change from baseline was significantly greater for pitolisant (-6.1) compared with placebo (-2.3; P < 0.001). Significantly more pitolisant-treated patients were classified as treatment responders: ESS score reduction ≥3, 69.0% in the pitolisant group versus 35.1% in the placebo group (P = 0.001); final ESS score ≤10, 36.2% versus 10.5%, respectively (P = 0.005). On the MWT, mean sleep latency increased from 3.5 min to 10.4 min with pitolisant and from 3.4 min to 6.8 min with placebo (P = 0.017). Least-squares mean change in the weekly rate of cataplexy was significantly greater for pitolisant (-14.5; baseline, 23.9; final, 9.4) compared with placebo (-0.1; baseline, 23.1; final, 23.0; P = 0.004). Headache was the most common adverse event with pitolisant. CONCLUSIONS: Pitolisant, at once-daily doses up to 35.6 mg, was efficacious for reducing excessive daytime sleepiness and cataplexy in patients with severe narcolepsy symptom burden.
STUDY OBJECTIVE: To evaluate the efficacy of pitolisant, a histamine 3 (H3)-receptor antagonist/inverse agonist, in adult patients with high burden of narcolepsy symptoms. METHODS: Data were pooled from two randomized, placebo-controlled, 7- or 8-week studies of pitolisant (titrated to a potential maximum dose of 35.6 mg/day) in adults with narcolepsy. Analyses included three independent patient subgroups: Epworth Sleepiness Scale (ESS) baseline score ≥16, Maintenance of Wakefulness Test (MWT) sleep latency ≤8 min, and ≥15 cataplexy attacks per week. RESULTS: The analysis populations included 118 patients for ESS (pitolisant, n = 60; placebo, n = 58), 105 for MWT (pitolisant, n = 59; placebo, n = 46), and 31 for cataplexy (pitolisant, n = 20; placebo, n = 11). On the ESS, least-squares mean change from baseline was significantly greater for pitolisant (-6.1) compared with placebo (-2.3; P < 0.001). Significantly more pitolisant-treated patients were classified as treatment responders: ESS score reduction ≥3, 69.0% in the pitolisant group versus 35.1% in the placebo group (P = 0.001); final ESS score ≤10, 36.2% versus 10.5%, respectively (P = 0.005). On the MWT, mean sleep latency increased from 3.5 min to 10.4 min with pitolisant and from 3.4 min to 6.8 min with placebo (P = 0.017). Least-squares mean change in the weekly rate of cataplexy was significantly greater for pitolisant (-14.5; baseline, 23.9; final, 9.4) compared with placebo (-0.1; baseline, 23.1; final, 23.0; P = 0.004). Headache was the most common adverse event with pitolisant. CONCLUSIONS: Pitolisant, at once-daily doses up to 35.6 mg, was efficacious for reducing excessive daytime sleepiness and cataplexy in patients with severe narcolepsy symptom burden.
Authors: Stephanie P Fabara; Juan Fernando Ortiz; Anas Anas Sohail; Jessica Hidalgo; Abbas Altamimi; Belen Tama; Urvish K Patel Journal: Cureus Date: 2021-07-01