Topline data showed that the novel oxybate candidate demonstrated significant differences compared to placebo in the change in the weekly number of cataplexy attacks and the change in Epworth Sleepiness Scale score, the primary and secondary end points, respectively.
Michael J. Thorpy, MBChB
Positive top-line data has been announced by Jazz Pharmaceuticals regarding JZP-258, its investigational cataplexy and excessive daytime sleepiness in patients with narcolepsy.1
The findings thus far have shown that the novel oxybate candidate demonstrated highly significant differences compared to placebo as measured by the change in the weekly number of cataplexy attacks and the change in Epworth Sleepiness Scale (ESS) score, the primary and secondary end points, respectively.
"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," said Jed Black, MD, the senior vice president of Sleep and CNS Medicine at Jazz Pharmaceuticals and adjunct professor at the Stanford University Medical Center’s Center for Sleep Sciences and Medicine, in a statement. "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."
Additionally, patients who were randomized to JZP-258 showed a clinically meaningful conservation of efficacy, while those randomized to placebo experienced a statistically significant worsening for both ESS and cataplexy end points.
As for safety, the therapy was shown to be consistent with the most commonly reported treatment-emergent adverse events being headache, nausea, dizziness, cataplexy, nasopharyngitis, decreased appetite, influenza, diarrhea, and vomiting. No other events occurred at a rate greater than 5%.
"Narcolepsy is a chronic, debilitating disease and is associated with an increased risk of comorbidities," said Michael J. Thorpy, MBChB, the director of the Sleep-Wake Disorders Center at Montefiore Health System in the Bronx, New York, in a statement. "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."
Thorpy told NeurologyLive previously that despite there being number of medications used for narcolepsy, it remains difficult to treat. The history of its treatment originated with traditional stimulants, such as methylphenidate and the amphetamine—which are still used—but, he said, “they have significant adverse effects. People can develop tolerance to them, there can be mental stimulation, psychosis and irritability, and there can be cardiac consequences. So, they’re not ideal even though they help keep people awake.”
The phase 3 study included 201 patients, 134 of which were randomized. The cohort comprised of a heterogeneous population, including those treated previously with sodium oxybate (Xyrem, Jazz), those naïve to Xyrem, and with or without other anti-cataplectic treatments. According to Jazz, the randomized-withdrawal study design was intended to measure efficacy (more specifically, the maintenance of effect) for patients who remained on active treatment, and worsening for patients who switched to placebo.
The company has stated that it plans to submit the phase 3 study data for presentation at an upcoming medical meeting, and in combination with interim data from the ongoing 24-week open-label safety study, this data will be included in the planned submission of a New Drug Application (NDA) to the FDA.
1. Jazz Pharmaceuticals Announces Positive Top-line Results from Phase 3 Study of JZP-258 in Adult Narcolepsy Patients with Cataplexy and Excessive Daytime Sleepiness [press release]. Dublin, Ireland: Jazz Pharmaceuticals; Published March 26, 2019. prnmedia.prnewswire.com/news-releases/jazz-pharmaceuticals-announces-positive-top-line-results-from-phase-3-study-of-jzp-258-in-adult-narcolepsy-patients-with-cataplexy-and-excessive-daytime-sleepiness-300819008.html. Accessed March 27, 2019.