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Additional data of a phase 2 study presented at the 2024 SLEEP Annual Meeting demonstrated that pitolisant significantly improved in secondary end points among patients with myotonic dystrophy type 1.
Kumar Budur, MD, MS
(Credit: LinkedIn)
New data from a phase 2 signal detection study (NCT04886518) presented at the 2024 SLEEP Annual Meeting, held June 1 to 5, in Houston, Texas, showed that Harmony Biosciences’ pitolisant (Wakix) reduced excessive daytime sleepiness (EDS) and fatigue in adults with myotonic dystrophy type 1 (DM1).1
Overall, patients with DM1 on high- (n= 8) and low-dose (n = 8) pitolisant reported mean changes of –2.5 and –1.0 in Daytime Sleepiness Scale (DSS) in comparison with changes of –0.2 for those on placebo (n = 9) after 11 weeks of treatment. On Epworth Sleepiness Scale (ESS), patients on high- and low-dose pitolisant reported mean changes of –4.9 and 1.3 in comparison with changes of –0.1 for those on placebo, suggesting the higher dose group had a stronger efficacy signal from baseline to week 11.
"More than 80 percent of patients with DM1 experience EDS and fatigue, which patient-reported outcomes research has shown to be nearly as debilitating as the primary symptoms of DM1, namely myotonia and muscle weakness," Kumar Budur, MD, MS, chief medical and scientific officer at Harmony Biosciences, said in a statement.1 "The findings from our signal detection study evaluating pitolisant, which is believed to promote wakefulness through histamine, present an exciting opportunity to develop new treatments for EDS and fatigue in DM1, narcolepsy, and the other sleep/wake disorders we are investigating through our lifecycle management programs that will involve Next-Generation formulations of pitolisant."
This study was a randomized, double-blind, placebo-controlled trial aimed to assess the efficacy and safety of pitolisant in the treatment of EDS and other nonmuscular symptoms in adults with DM1. Patients diagnosed with DM1 were enrolled in an 11-week double-blind treatment phase which included a 3-week titration period and an 8-week stable dose period. Investigators had participants randomized to a high or low dose of pitolisant, or a matching placebo. The primary efficacy end point was the change from baseline to week 11 in DSS score while secondary efficacy end points included the change in ESS score, Fatigue Severity Scale (FSS) score, Clinical Global Impression of Severity (CGI-S) score, and Myotonic Dystrophy Health (MDHI) Index score.
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Additional results showed that patients on high- and low-dose pitolisant displayed mean changes of –0.9 and –0.4 on FSS score compared with changes of –0.1 observed in the placebo group. On CGI-S, patients on high- and low-dose pitolisant revealed mean changes of –0.9 and –0.2 in comparison with changes of –0.1 for those on placebo. Furthermore, patients on high- and low-dose pitolisant reported mean changes of –0.9 and –2.9 on MDHI vs changes of 0.4 among those in the placebo group.
Thus, the findings suggest that the overall disease burden signaled greater improvement for pitolisant compared with placebo, with the higher dose group revealing a stronger efficacy signal. Investigators reported similar adverse event rates for both pitolisant and placebo groups. Notably, researchers noted that the safety and tolerability findings of pitolisant among patients with DM1 were consistent with previous studies.
"Given the potential opportunity of pitolisant for treating EDS and fatigue in patients with DM1, we plan to progress our DM1 development program through a pivotal phase 3 study using the Next-Generation 2 (NG2) formulation of pitolisant, which is designed to deliver an optimized pharmacokinetic profile and higher dosage strength," Budur added in the statement.1 "The NG2 formulation could be promising given the positive findings we observed across the EDS and fatigue endpoints within the higher dose pitolisant treatment arm. These efforts are integral to our broader life cycle management programs, which, if successful, could benefit over 100,000 patients living with unmet medical needs."
Pitolisant was originally approved for the treatment of EDS in patients with narcolepsy in 2019 and is only investigational for those with DM1. It had its indication expanded in 2020 to include the treatment of cataplexy in adults with narcolepsy, with results from the HARMONY CTP (NCT018000450) and HARMONY 1 (NCT01067222) trials serving as the basis for the decision.2 More recently, the FDA granted approval to pitolisant for the treatment of EDS in pediatric patients aged 6 years and older with narcolepsy.3 In addition, the agency issued pitolisant a complete response for the treatment of cataplexy in pediatric patients with narcolepsy.
The therapy remains in development for other conditions such as Prader-Willi syndrome and idiopathic hypersomnia (IH). Most recently, in October, topline results from the phase 3 INTUNE study (NCT05156047) showed that pitolisant failed to distinguish itself from placebo in improving EDS in patients with IH; however, it reached statistical significance in additional prespecified end points of disease severity and functional status. Approximately 83% of patients with IH who completed the 8-week open-label treatment period with pitolisant had a decrease of at least 3 points on the ESS and an average ESS change from baseline of –9.4 points.4
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