Mixed Sodium Oxybates Improve Idiopathic Hypersomnia

In a phase 3 study (NCT03533114) of mixed salt oxybates (MSO) (Xywav; Jazz Pharmaceuticals, Philadelphia, PA) for treatment of idiopathic hypersomnia (IH) showed improvement on multiple measures. All participants first received treatment with MSO for up to 14 weeks, which was then replaced with either the individual's stable dose of MSO or a placebo for 2 weeks in a randomized and double-blind protocol.

In the weeks when MSO was replaced with stable dose or placebo, those who had placebo (n=59) had significant worsening of IH, as measured by the Epworth Sleepiness Scale (ESS) score, Patient Global Impression of Change (PGIc), and the Idiopathic Hypersomnia Severity Scale (IHSS). Comparing ESS from the end of pretreatment to the end of the withdrawal period, those given placebo had an average decrease of 6.5 points (least squares mean; 95% CI: -7.99 to -5.03; P<.001). Scores on th eIHSS also worsened by a median 12.0 points (95% CI: -15.0 to -8.0; P<.001). Only 21% of those who continued on their stable dose rate change as minimal on the PGIc vs 88% of those who received placebo (P<.001)

Improvement in ESS score with MSO before the withdrawal period was from a mean of 15.7+/-3.77 to a mean of 6.1+/-3.99. Improvement in IHSS score with MSO before the withdrawal period was from a mean of 31.6+/-8.34 at study entry to a mean of 15.3+/-8.46.

"The dramatic improvements Xywav provided for participants within this study give hope to not only those living with idiopathic hypersomnia, but also to their families, friends and care teams," said Yves Dauvilliers, MD, director of the Sleep Disorders Centre at the Gui de Chauliac Hospital in Montpellier, France and lead investigator of the phase 3 study. "People with idiopathic hypersomnia sleep a normal, or longer than normal, amount of sleep each night, but still experience excessive sleepiness during the day. If the new indication is approved by the FDA, I believe Xywav will make an immediate impact on patients living with idiopathic hypersomnia."

The most common adverse events were anxiety (10.4%), dizziness (11.7%), headache (16.2%), nausea (21.4%), and vomiting (10.4%).

These data were presented at the American Academy of Neurology Virtual Annual Meeting April 17-22, 2021.