Jazz Pharmaceuticals plc announced positive top-line results from a global, double-blind, placebo-controlled, randomized-withdrawal, multicenter Phase 3 study evaluating the efficacy and safety of JZP-258 for the treatment of cataplexy and excessive daytime sleepiness (EDS) in adult patients with narcolepsy. JZP-258 is a novel oxybate product candidate with a unique composition of cations resulting in 92% less sodium than Xyrem (sodium oxybate).
The Phase 3 study demonstrated highly statistically significant differences in the primary endpoint that measured the change in the weekly number of cataplexy attacks and the key secondary endpoint of change in Epworth Sleepiness Scale (ESS) score with JZP-258 compared to placebo. In this study, patients were randomized to either continue JZP-258 or to receive placebo. Patients randomized to JZP-258 showed clinically meaningful maintenance of efficacy for both cataplexy and EDS, while a statistically significant worsening for both cataplexy and ESS endpoints was observed in the placebo group compared with JZP-258.
The safety profile of JZP-258 is consistent with sodium oxybate. The most commonly reported treatment-emergent adverse events that occurred in ? 5% of patients who received JZP-258 were headache, nausea, dizziness, cataplexy, nasopharyngitis, decreased appetite, influenza, diarrhea, and vomiting. Two patients experienced serious adverse events (SAEs) that were considered by the investigator to be treatment-related.
Jazz will submit the Phase 3 study data for presentation at an upcoming medical meeting. Data from the completed Phase 3 study and interim data from the ongoing 24-week open-label, safety study will be included in the planned submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA).
“Jazz is committed to developing new treatment options that serve unmet needs for patients living with sleep disorders, including JZP-258, a novel oxybate product candidate with 92% less sodium than sodium oxybate,” says Jed Black, MD, senior vice president, Sleep and CNS Medicine at Jazz Pharmaceuticals and adjunct professor, Stanford University Medical Center, Stanford Center for Sleep Sciences and Medicine, in a release. “We are deeply grateful to the patients and investigators who participated in this study, and we will meet with the FDA to discuss the Phase 3 results in narcolepsy and our NDA submission plans, with the goal of making JZP-258 available to narcolepsy patients.”
Michael Thorpy, M.D., director, Sleep-Wake Disorders Center, Montefiore Health System in Bronx, NY, says, “Narcolepsy is a chronic, debilitating disease and is associated with an increased risk of comorbidities. An extensive body of evidence has established that excessive consumption of sodium is linked with an increased risk of stroke, cardiovascular disease and other adverse outcomes. Patients with narcolepsy may require lifelong medication, and there is a need for a new, low-sodium oxybate formulation.”
