Positive data from the Phase 3 study of Jazz Pharmaceuticals plc’s investigational medicine, JZP-258, for the treatment of cataplexy and excessive daytime sleepiness (EDS) in adults with narcolepsy were presented at World Sleep 2019 in Vancouver, Canada.
“We are pleased with the positive results from the Phase 3 study of JZP-258, which demonstrate the efficacy of JZP-258 for the treatment of cataplexy and excessive daytime sleepiness in narcolepsy,” says Jed Black, MD, senior vice president, Sleep and Neuroscience at Jazz Pharmaceuticals and adjunct professor, Stanford University Medical Center, Stanford Center for Sleep Sciences and Medicine, in a release. “These data support the efficacy and overall safety profile of a lower-sodium oxybate formulation for people living with narcolepsy, a chronic condition that may require lifelong therapy. There is broad consensus among health care organizations, like the National Academy of Sciences and American Heart Association, that lowering sodium intake lowers the risk of cardiovascular disease. We believe that JZP-258, if approved, will provide a clinically meaningful benefit to patients prescribed oxybate.”
The Phase 3 study of JZP-258 was a global, double-blind, placebo-controlled, randomized-withdrawal, multicenter study evaluating the efficacy and safety of JZP-258 in the treatment of cataplexy and EDS in adults with narcolepsy. The primary endpoint was the change in the weekly number of cataplexy attacks, and the key secondary endpoint was the change in the Epworth Sleepiness Scale (ESS) score with JZP-258 compared to placebo. The study enrolled 201 participants and randomized 134 participants, comprising a heterogeneous population, which included those previously treated with sodium oxybate and naïve to sodium oxybate, with or without other anticataplectic treatments. A randomized-withdrawal study design aims to measure efficacy—specifically, maintenance of effect—for participants who continue on active treatment, as well as worsening for participants randomized to placebo.
The study design included an optimization and titration period of up to 12 weeks, a JZP-258 stable-dose period of two weeks, followed by 1:1 randomization to either JZP-258 or placebo for two weeks. After the completion of the double-blind, placebo-controlled treatment period, patients had the opportunity to receive JZP-258 in an optional 24 week open-label safety extension period. More information about the study design is available at www.clinicaltrials.gov (identifier: NCT03030599).
During the double-blind withdrawal period, there was a significant increase in median weekly number of cataplexy attacks in participants randomized to placebo compared with participants randomized to JZP-258 (median [Q1, Q3]: 2.35 [0.00, 11.61] vs 0.00 [−0.49, 1.75], respectively; treatment difference, P