The combination agent breaks ground as the first treatment approved for this indication.
The US Food and Drug Administration (FDA) has approved JZP-258 (Xywav) for the treatment of idiopathic hypersomnia, making it the first treatment cleared for this indication. The approval was granted to Jazz Pharmaceuticals.
The combination agent of calcium, magnesium, potassium, and sodium oxybates will be available to patients in the fourth quarter of 2021 following Risk Evaluation and Mitigation Strategies (REMS) implementation.
The company announced the acceptance of its supplemental new drug application (sNDA) for JZP-258 in February, which included data from a positive phase 3 study (NCT03533114) that showed the investigational agent was effective and safe for adults with idiopathic hypersomnia.
The oral solution received fast track designation from the FDA in September 2020 for this indication, and in December was granted a rolling submission, allowing for the submission of portions of the application as completed.
Idiopathic hypersomnia is a debilitating neurologic sleep disorder characterized by chronic excessive daytime sleepiness (EDS). A majority of physicians in the space have turned to off-label use of wake-promoting therapies typically used in patients with narcolepsy to help address the sleepiness issues.
"We are excited that with today's approval Xywav will become the first and only medicine indicated to treat idiopathic hypersomnia, a unique medical condition that can have significant effects on the lives of those diagnosed with the condition," Bruce Cozadd, chairman and chief executive officer, Jazz Pharmaceuticals, said in a statement.
"This milestone exemplifies our patient-focused R&D strategy and internal development capabilities, and underscores oxybate as a key growth opportunity for Jazz. With this launch we will have achieved our goal of five product launches in two years."
The double-blind, multicenter, randomized phase 3 trial featured patients who had EDS associated with idiopathic hypersomnia, and all of those treated with the agent experienced clinically meaningful improvements in Epworth Sleepiness Scale (ESS) scores–the primary end point–during the open-label titration period.
A randomized withdrawal portion of the study included 115 patients who were assessed on primary and key secondary end points including Patient Global Impression of Change (PGIC) and Idiopathic Hypersomnia Severity Scale (IHSS).
Those who received JZP-258 reported clinically meaningful maintenance of efficacy as measured by all 3 evaluations. Furthermore, highly statistically significant worsening was observed for those who received placebo compared with JZP-258 for ESS (P <.0001), PGIC (P < .0001), and IHSS (P < .0001).
Xywav has a Boxed Warning as a central nervous system (CNS) depressant and for its potential for abuse and misuse. The most common adverse reactions, occurring in at least 5% of adults in the phase 3 study, were nausea, headache, dizziness, anxiety, insomnia, decreased appetite, hyperhidrosis, vomiting, diarrhea, dry mouth, parasomnia, somnolence, fatigue, and tremor.
JZP-258 originally received approval for the treatment of cataplexy or EDS in patients 7 years of age or older with narcolepsy in July 2020. The basis of that approval was built on data from a phase 3 double-blind, placebo-controlled, randomized-withdrawal, multicenter study, for which the drug demonstrated statistically significant differences (P <.0001) in the weekly number of cataplexy attacks and ESS scores compared with placebo.
"Idiopathic hypersomnia can have a significant impact on the social, educational and occupational functioning of people living with the condition. Today's FDA approval is a major milestone for the entire idiopathic hypersomnia community as Xywav becomes the first medicine approved to manage this chronic sleep disorder," Dianne Powell, board chair and chief executive officer, Hypersomnia Foundation, said in a statement.
"Our mission and values have consistently centered around supporting patients and scientific discovery and this announcement truly provides a sense of hope for those living with idiopathic hypersomnia."