The Jazz Pharmaceuticals’ product, which was FDA approved in August 2021, demonstrated clinically meaningful differences compared with placebo on several secondary end points, including impression of change scales and various and questionnaires.
After becoming the first FDA-approved treatment for patients with idiopathic hypersomnia, Jazz Pharmaceuticals has released additional positive data from its supporting phase 3, double-blind study (NCT03533114) of JZP-258 (Xywav), a formulation of calcium, magnesium, potassium, and sodium oxybates.1,2
All told, the medication demonstrated clinically meaningful and statistically significant differences compared with placebo in both the primary end point—change in Epworth Sleepiness Scale (ESS) score—and several other secondary end points.
"The full data set from the largest global phase 3 trial in adults with idiopathic hypersomnia represents a major advance in this condition and will enable physicians to make more informed, evidence-driven treatment decisions," lead investigator Yves Dauvilliers, MD, PhD, director, Sleep and Wake Disorders Center, Gui de Chauliac Hospital, said in a statement.1 "The trial results demonstrate that Xywav offers significant and clinically meaningful improvements to multiple aspects of this debilitating condition that can benefit the sleep and daily lives of adults diagnosed with this unique sleep disorder."
A total of 154 adults with idiopathic hypersomnia, aged 19 to 75 years, were included in the study and dosed for 3 periods. First, patients completed an open-label period on the study drug for 10-14 weeks to determine optimal dosing. For the next 2 weeks, patients received stable, optimized doses of JZP-258, with a median of 4.5 grams nightly (interquartile range [IQR], 3.0-5.0) for 21 patients on 1-dose regimen and 7.5 grams nightly (IQR, 6.5-8.1) for 93 patients on 2-dose regimen. The remaining 40 patients changed dosing regiments 1 or more times.
Patients then entered the double-blind randomized withdrawal period (DBRWP), where they received either the optimized dose or placebo for 2 weeks and were evaluated on changes in ESS scores beginning from the end of the stable dose period (SDP). During the DBRWP, ESS scores increased (representing a status worsening) in participants randomly assigned to placebo but remained stable in those assigned to JZP-258 (least squares mean difference: –6.5 [95% CI, –8.0 to –5.0]; P <.0001).
Throughout the trial, common treatment-emergent adverse events (TEAEs), reported by more than 10% of the participants, included nausea (22%), headache (18%), dizziness (12%), anxiety (11%), and vomiting (11%). Nine serious TEAEs, none of which were related to the study drug, were reported across 4 participants. Notably, no deaths occurred during the trial.
At the beginning of the study, patients recorded mean idiopathic hypersomnia severity scale (IHSS) scores of 32.1 (standard deviation [SD], 8.0), indicating severe disease. Those who continued treatment with JZP-258 through the DBRWP demonstrated showed stable mean IHSS scores (range, 15.5 [SD, 9.2] to 16.9 [SD, 8.1]) whereas those randomized to placebo had IHSS scores increase from 15.2 (SD, 7.8) to 28.5 (SD, 9.0), indicating worsening. The between-group differences in IHSS score changes were statistically significant (P <.0001).
At the conclusion of the study, JZP-258 showed clinically meaningful differences compared with placebo on several secondary end points including Patient Global Impression of Change (difference in proportion worsened, –67% [95% CI, –80 to –53]; P <.0001). Investigators documented benefits with JZP-258 over placebo in other assessments such as Clinical Global Impression of Change; the Functional Outcomes of Sleep Questionnaire, short version; the visual analog scale for sleep inertia; and the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem.
"Xywav is the only FDA-approved medicine available to treat idiopathic hypersomnia, providing clinicians with an effective and meaningful option for their patients to help relieve symptoms like sleep inertia and excessive daytime sleepiness," Rob Iannone, MD, MSCE, executive vice president, research and development, and chief medical officer, Jazz Pharmaceuticals, said in a statement.1 "We are committed to addressing the debilitating unmet needs of patients with neurological disorders through the development of novel medicines that can transform lives, and our launch of Xywav for use in idiopathic hypersomnia is one example of Jazz's evolved R&D capabilities."
The FDA’s decision to make JZP-258 the first approved therapy for idiopathic hypersomnia came in August 2021, and was based on data from this study. The oral solution was originally approved for the treatment of cataplexy or excessive daytime sleepiness in patients 7 years or older with narcolepsy in July 2020.