The Food and Drug Administration (FDA) has approved Xywav® (calcium, magnesium, potassium, and sodium oxybates) oral solution for the treatment of idiopathic hypersomnia in adults.
Xywav is an oxybate product believed to exert its therapeutic effects through GABAB during sleep at noradrenergic and dopaminergic neurons, as well as at thalamocortical neurons. It contains the same oxybate concentration as Xyrem (sodium oxybate; Jazz Pharmaceuticals), but with a unique composition of cations resulting in 92% less sodium (approximately 1000 to 1500mg/night).
The approval was based on data from a multicenter, randomized withdrawal, double-blind, placebo-controlled phase 3 study (ClinicalTrials.gov Identifier: NCT03533114) that assessed the efficacy and safety of Xywav in adults with idiopathic hypersomnia. The study included an open-label titration period followed by a randomized withdrawal period, which included 115 patients who received either Xywav or placebo for 2 weeks.
Findings showed that treatment with Xywav led to clinically meaningful improvements in Epworth Sleepiness Scale (ESS) score during the open-label titration period (primary endpoint; P <.0001). Xywav was also associated with significant improvements in Patient Global Impression of Change (PGIc) (P <.0001) and Idiopathic Hypersomnia Severity Scale (IHSS) (P <.0001) compared with placebo (secondary endpoints).
During the randomized withdrawal period, Xywav demonstrated clinically meaningful maintenance of efficacy for ESS, PGIc and IHSS.
The most common adverse reactions observed with Xywav in adults were nausea, headache, dizziness, anxiety, insomnia, decreased appetite, hyperhidrosis, vomiting, diarrhea, dry mouth, parasomnia, somnolence, fatigue and tremor.
Xywav, a Schedule III controlled substance, carries a Boxed Warning regarding central nervous system (CNS) depression and the potential for abuse and misuse. The product is only available through a restricted distribution program.
Xywav is expected to be available to patients with idiopathic hypersomnia later this year following Risk Evaluation and Mitigation Strategy (REMS) implementation. The product is supplied as 0.5g/mL total salts (equivalent to 0.413g/mL of oxybate) in 180mL bottles.
“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,” said Bruce Cozadd, chairman and chief executive officer of Jazz Pharmaceuticals.
Xywav is also approved for the treatment of cataplexy or excessive daytime sleepiness in patients 7 years of age and older with narcolepsy.
- Jazz Pharmaceuticals announces U.S. FDA approval of Xywav® (calcium, magnesium, potassium, and sodium oxybates) oral solution for idiopathic hypersomnia in adults. News release. Jazz Pharmaceuticals plc. Accessed August 12, 2021. https://www.prnewswire.com/news-releases/jazz-pharmaceuticals-announces-us-fda-approval-of-xywav-calcium-magnesium-potassium-and-sodium-oxybates-oral-solution-for-idiopathic-hypersomnia-in-adults-301354616.html.
- Xywav [package insert]. Palo Alto, CA: Jazz Pharmaceuticals, Inc.; 2021.