Patients diagnosed with idiopathic hypersomnia -- characterized by excessive daytime sleepiness, prolonged nighttime sleep, and sleep inertia -- appeared to benefit from a novel oxybate treatment with 92% less sodium than sodium oxybate (Xyrem), a researcher reported.
Significant worsening was observed in Epworth Sleepiness Scale (ESS) scores for patients receiving placebo compared with lower-sodium oxybate (Xywav), for a mean difference of -6.51 (95% CI -7.99 to -5.03, P<0.0001), reported Yves Dauvilliers, MD, PhD, of University of Montpelier in France.
"In this phase III, placebo-controlled, double-blind, randomized withdrawal study in participants with idiopathic hypersomnia, lower-sodium oxybate demonstrated statistically significant and clinically meaningful effects on excessive daytime sleepiness, Idiopathic Hypersomnia Severity Scale score, and self-reported Global Impression of Change," he said in an oral presentation at the American Academy of Neurology virtual meeting.
Idiopathic hypersomnia is associated with decreased health-related quality of life, impairment in social and work functioning, and increased motor vehicle accidents.
"These are people who sleep too much, and still have excessive daytime sleepiness; they are always sleepy, and we don't know why that is," Steven Feinsilver, MD, of the Zucker School of Medicine at Hofstra University/Northwell Health, told 乌鸦传媒.
While sodium oxybate is sometimes used to treat patients, it does not have regulatory approval for treatment of idiopathic hypersomnia, nor do any other drugs.
Feinsilver said that he is not convinced that using any treatment for the disorder is the way to go, noting that oxybate can induce such a deep sleep that a person might not be able to hear a smoke alarm or a child crying. "You should not take this drug if you live alone," he said.
The study included 154 patients (mean age 40 years, 68% women) with a mean ESS score of 16. They underwent a 30-day screening period, and then a 2-week titration and optimization treatment period followed by 2 weeks on lower-sodium oxybate. During that period, mean ESS scores steadily decreased to a mean of 7.
At that point, the participants were randomized to either continue on lower-sodium oxybate or receive placebo. At the end of the withdrawal portion of the study, the patients on placebo rebounded to a mean of 15 in ESS score, while those on lower-sodium oxybate stabilized at about a score of 7.
Additionally, about 88% of patients who were in the placebo arm had worsening on the Patient Global Impression of Change scale compared with about 21% of patients on lower-sodium oxybate, a difference that was statistically significant (P<0.0001), Dauvilliers reported.
He noted that the scores on the Idiopathic Hypersomnia Severity Scale also deteriorated among the placebo patients in the withdrawal phase of the trial (estimated median difference -12.00, 95% CI -15.0 to -8.0, P<0.0001).
Treatment-emergent adverse events (TEAEs) included nausea (21.4%), headache (16.2%), dizziness (11.7%), anxiety (10.4%), and vomiting (10.4%). Serious TEAEs occurred in four participants (non-cardiac chest pain, rhabdomyolysis, syncope, and nephrolithiasis/pyelonephritis), but none were thought to be related to the study drug.
Treatment with oxybate can cost thousands of dollars a month, as it is nearly impossible for physicians to get third-party payers to cover the treatment, Feinsilver noted. Sodium oxybate is a liquid agent that is quite salty, and some people can't handle the taste or the sodium content.
However, when the drug is given to patients with narcolepsy, they achieve really deep sleep that appears to reduce daytime sleepiness, he said.
"I think it is unclear if the agent has the same impact on idiopathic hypersomnia patients," he added. "If you give people who have trouble getting good sleep a drug that gives amazingly deep sleep, it is likely that they will feel better during the daytime."
He also noted it is difficult to determine if the patient really has idiopathic hypersomnia. "Idiopathic hypersomnia is a diagnosis of exclusion. There is no one test that tells you 'oh, that's what it is,'" he said. Generally, a doctor rules out all other possible reasons for excessive daytime sleepiness -- such as narcolepsy, sleep apnea, or depression -- before diagnosing idiopathic hypersomnia.
Disclosures
The trial was supported by Jazz Pharmaceuticals.
Dauvilliers disclosed relationships with Jazz Pharmaceuticals, UCB Pharma, Avadel, Idorsia, Takeda, Theranexus, and Bioprojet.
Feinsilver disclosed no relationships with industry.
Primary Source
American Academy of Neurology
Dauvilliers Y, et al "Efficacy and safety of lower-sodium oxybate in a phase 3, placebo-controlled, double-blind, randomized withdrawal study in adult participants with idiopathic hypersomnia" AAN 2021.