The novel oxybate agent is seeking an indication for the treatment of cataplexy and excessive daytime sleepiness in those 7 years and older with narcolepsy. The PDUFA date is July 21, 2020.
Robert Iannone, MD, MSCE
The FDA has accepted a new drug application (NDA) for Jazz Pharmaceuticals’ JZP-258, an investigational, novel oxybate agent for the treatment of cataplexy and excessive daytime sleepiness in those 7 years and older with narcolepsy.1
The agency has set the Prescription Drug User Fee Act (PDUFA) action date for July 21, 2020. Currently, the only approved agent for this indication is sodium oxybate (Xyrem), which has 92% more sodium, according to Jazz.
"We developed JZP-258 to be a safer and long-term treatment option for patients. JZP-258 represents between 1000 and 1500 mg daily reduction of sodium for patients currently treated with Xyrem, depending on the dose," said Robert Iannone, MD, MSCE., executive vice president, research and development, Jazz Pharmaceuticals, in a statement.1 "Given the broad scientific consensus that reducing daily sodium consumption is associated with clinically meaningful reductions in blood pressure and cardiovascular disease risk, we believe that JZP-258 has the potential to be an important treatment option for patients living with the life-long condition of narcolepsy.”
Iannone added that literature suggests that those with narcolepsy are at increased risk of comorbidities that include obesity, hypertension, diabetes, and dyslipidemia.
The NDA is supported by data from a phase 3 global, double-blind, placebo-controlled study. JZP-258 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. The treatment group showed clinically meaningful conservation of efficacy, while the placebo group experienced a significant worsening for both end points.
In data presented at World Sleep 2019, it showed efficacy and safety in treating patients with narcolepsy who have cataplexy. The study featured a randomized-withdrawal design, aimed at measuring the maintenance of effect for participants who continued on active treatment as well as worsening for those randomized to placebo. Data suggested a significant increase in the weekly number of cataplexy attacks in those randomized to placebo compared to JZP-258, a difference of 2.35 attacks per week (P <.0001).3
Overall, the study enrolled 201 subjects, of which 134 were randomized to either JZP-258 or placebo. The cohort included patients who were both naïve to and had been treated with sodium oxybate, with or without other antinarcoleptic therapy. Patients went through an up to 12-week optimization and titration period followed by a 2-week stable dose period with JZP-258, and then a 2-week randomization period to treatment or placebo.
During the double-blind withdrawal period, participants randomized to placebo experienced 2.35 (interquartile range [IQR], 0.00 to 11.61) weekly cataplexy attacks compared to 0 (IQR, —0.49 to 1.75) in the JZP-258 group. Additionally, significant increases in median ESS scores were observed in the placebo group (median, 2.0 [IQR, 0.0 to 5.0]) compared to the treatment group (median, 0 [IQR, –1.0 to 1.0]; P <.0001).
1. Jazz Pharmaceuticals Announces FDA Acceptance of New Drug Application for JZP-258 for Cataplexy and Excessive Daytime Sleepiness Associated with Narcolepsy [press release]. Dublin, Ireland: Jazz Pharmaceuticals; Published March 25, 2020. Accessed March 25, 2020. investor.jazzpharma.com/news-releases/news-release-details/jazz-pharmaceuticals-announces-fda-acceptance-new-drug
2. 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. Accessed March 25, 2020. 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.
3. Jazz Pharmaceuticals Presents Positive JZP-258 Phase 3 Study Data at World Sleep 2019 [press release]. Dublin, Ireland: Jazz Pharmaceuticals; Published September 25, 2019. Accessed March 25, 2020. prnewswire.com/news-releases/jazz-pharmaceuticals-presents-positive-jzp-258-phase-3-study-data-at-world-sleep-2019-300925650.html.