Investigators noted that, when considered with efficacy findings in narcolepsy, pitolisant has a favorable risk-benefit profile representative of advancement in the treatment of excessive daytime sleepiness and cataplexy in adult patients.
Catherine Scart-Grès, MD
Results of a recent analysis of safety data evaluating pitolisant’s impact on patients with narcolepsy suggest that the therapy is both generally safe and well tolerated.1
The data on Bioprojet Pharma and Harmony Biosciences’ investigational selective histamine 3 (H3) receptor antagonist/inverse agonist were pooled from 4 placebo-controlled studies, including more than 300 patients. Previously, the FDA granted a priority review designation to the first-in-class molecule for the potential treatment of excessive daytime sleepiness (EDS) and/or cataplexy in those with narcolepsy.2
The analysis of these pooled findings was presented at SLEEP 2019, June 8-12 in San Antonio, Texas. Catherine Scart-Grès, MD, head, clinical development, Bioprojet Pharma, led the group of investigators.
“Considered together with the efficacy findings, pitolisant offers a favorable risk/benefit profile and represents a potential advancement in the treatment of EDS and cataplexy in adult patients with narcolepsy,” Scart-Grès and colleagues wrote. The overall incidence of adverse events (AEs) in the dataset was 49.4% with pitolisant compared to 41.2% with placebo.
Over the course of the 7- to 8-week studies included, pitolisant was dosed to a maximum of 35.6 mg (occurred in 3 studies, 39.5% of patients) or ≤17.8 mg (occurred in 1 study, 60.5% of patients) in a flexible manner. In the studies which included 35.6 mg, 68.5% of patients were titrated to that dose. The safety evaluations were conducted for AEs, vital signs, laboratory assessments, and electrocardiogram (ECG) measurements. Notably, there were no clinically relevant effects observed in any vital signs, laboratory findings, or ECG parameters.
In total, 303 patients were included, all of whom had been randomized to either pitolisant (n=172) or placebo (n=131) during their respective trial period. Patients were an average age of 39.2 with a mean duration of narcolepsy of 11.3 years. Of the 303 patients entered into the 4 studies, 94.2% of those given the study drug and 94.7% of those administered placebo completed the assessment.
The most common AEs, observed at a rate of >3% of pitolisant-treated patients, were headache (pitolisant, 18.0%; placebo, 13.7%), nausea (pitolisant, 5.2%; placebo, 3.1%), insomnia (pitolisant, 4.1%; placebo, 2.3 %), upper respiratory tract infection (pitolisant, 4.1%; placebo, 0.8%), back pain (pitolisant, 3.5%; placebo, 0.8%), and dizziness (pitolisant, 3.5%; placebo, 2.3%).
Serious AEs were reported in 1.2% (n=2) of pitolisant-treated patients and included a case of hemorrhoids and a case of pyelonephritis. Among the placebo group, 1 participant experienced a serious AE: a single case of biliary colic. Treatment-related discontinuation rates of 3.5% and 3.8% of patients in the pitolisant and placebo groups were reported, respectively.
“No new safety signals were identified from long-term, open-label studies in patients with narcolepsy,” Scart-Grès and colleagues noted.
In May 2018, the therapy was also granted breakthrough therapy and fast track designations from the FDA for its potential treatment for cataplexy in patients with narcolepsy. In a supporting 106-patient, phase 3 study, pitolisant was also shown to be well tolerated and efficacious in reducing cataplexy in patients with narcolepsy.3,4
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1. Scart-Grès C, Momah C, Roy M, Maski K, Piris S, Bogan RK. Sleep. 2019;42(Suppl 1):A244—A245. doi: 10.1093/sleep/zsz067.612. Presented at: SLEEP 2019. June 8-12, 2019; San Antonio, TX. Abstract 0614.
2. Harmony Biosciences Announces File Acceptance Of Its New Drug Application For Pitolisant [press release]. Plymouth Meeting, PA: Harmony Biosciences; Published February 12, 2019. harmonybiosciences.com/newsroom/harmony-biosciences-announces-file-acceptance-of-its-new-drug-application. Accessed June 11, 2019.
3. Harmony Biosciences Receives Breakthrough Therapy And Fast Track Designations For Pitolisant; Expanded Access Program For Pitolisant Is Open And Patients Are Being Enrolled [press release]. Plymouth Meeting, PA: Harmony Biosciences; Published May 21, 2018. harmonybiosciences.com/newsroom/harmony-biosciences-receives-breakthrough-therapy-and-fast-track. Accessed June 11, 2019.
4. Szakacs Z, Dauvilliers Y, Mikhaylov V, et al. Safety and efficacy of pitolisant on cataplexy in patients with narcolepsy: a randomised, double-blind, placebo-controlled trial. Lancet Neuro. 2017;16(3):200-207.