Once-Nightly Sodium Oxybate Meets Primary End Point in Phase 3 REVITALYZ Study for Idiopathic Hypersomnia

Newly presented findings from the phase 3 REVITALYZ study (NCT06525077) showed that extended-release sodium oxybate (Lumryz; Alkermes) met its primary end point in reducing excessive daytime sleepiness (EDS) compared with placebo among adults with idiopathic hypersomnia (IH).¹ Based on the phase 3 data, presented at the 2026 SLEEP Annual Meeting, held June 14-17, in Baltimore, Maryland, Alkermes noted that it plans to file a supplemental new drug application with the FDA by the end of 2026.²

Among 157 participants with IH enrolled, 83% were women and the mean age was 39.8 years. Investigators reported that approximately 26% of participants transitioned into the study from immediate-release oxybate therapy, whereas an additional subset had prior oxybate exposure. Findings showed that treatment with once-nightly sodium oxybate resulted in significant improvements in EDS compared with placebo, measured by the change in Epworth Sleepiness Scale (ESS) score (P <.0001), the primary end point.

“The data from REVITALYZ demonstrate the potential utility of once-nightly LUMRYZ as an effective treatment for excessive daytime sleepiness associated with IH, building upon its established therapeutic value in narcolepsy,” said Led by Richard K. Bogan, MD, FCCP, FAASM, principal of Bogan Sleep Consultants and associate clinical professor at the University of South Carolina School of Medicine, said in a statement.² “This is a community with limited approved therapeutic options. These findings constitute an important contribution to the clinical understanding of treatment approaches for patients with IH, for whom disruptive symptoms present particular treatment challenges.”

REVITALYZ enrolled adults with a primary diagnosis of IH, an ESS score greater than 11 among those not receiving oxybate therapy, and an average nightly sleep duration exceeding 7 hours. Participants underwent a 10-week dose-titration period followed by a 2-week stable-dose phase before entering a 2-week randomized withdrawal period, during which they were assigned in a 1:1 ratio to either continue once-nightly sodium oxybate or switch to placebo.¹

The primary efficacy end point was worsening in ESS total score during the randomized withdrawal period among participants switched to placebo compared with those who remain on active treatment. Key secondary outcomes included changes in Idiopathic Hypersomnia Severity Scale (IHSS), Functional Outcomes of Sleep Questionnaire (FOSQ), Patient Global Impression of Change, and Clinical Global Impression of Change scores.

At the conclusion of the double-blind randomized withdrawal period, the primary end point of ESS score and key secondary end points of PGI-C and IHSS score were evaluated in 104 participants. Compared with participants who continued once-nightly sodium oxybate, those randomized to placebo demonstrated statistically significant worsening from the end of the stable-dose period to the end of the withdrawal period in ESS (P <.0001), PGI-C (P <.0001), and IHSS (P <.0001).

In the REVITALYZ study, researchers noted that the safety profile of extended-release sodium oxybate was generally consistent with previously reported findings, with no new safety signals identified. The most frequently reported treatment-emergent adverse events occurring in at least 10% of participants were nausea, headache, anxiety, dizziness, and vomiting.

Once-nightly sodium oxybate is currently approved by the FDA for the treatment of EDS or cataplexy in patients 7 years of age and older with narcolepsy. The agent was developed to provide therapeutic drug exposure throughout the night following a single bedtime administration. The approach differs from currently available immediate-release oxybate therapies, which are commonly administered in 2 nightly doses, requiring patients to awaken approximately 2.5 to 4 hours after sleep onset for a second dose.

READ MORE: Phase 3 Data Support Sustained Safety, Symptom Improvement with Pitolisant in Idiopathic Hypersomnia

IH is a chronic neurologic sleep disorder characterized by excessive daytime sleepiness, prolonged sleep duration, unrefreshing sleep, and sleep inertia that can substantially impair daily functioning and quality of life. Although treatment options have expanded in recent years, the disorder remains associated with significant symptom burden, and many patients continue to experience persistent daytime impairment despite available therapies.

The study enters an evolving treatment landscape for IH. In 2021, the FDA approved calcium, magnesium, potassium, and sodium oxybates (Xywav) as the first therapy specifically indicated for adults with IH, based on findings from a phase 3 randomized withdrawal trial demonstrating improvements in sleepiness and overall symptom burden.³ Additional therapies, including pitolisant (Wakix; Harmony Biosciences) and orexin-targeted agents, are also being investigated as potential treatment options for the disorder.⁴

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REFERENCES
1. Bogan RK, Harsh J, Ibrahim S, et al. REVITALYZ: A Phase 3, Double-Blind, Placebo-Controlled, Randomized Withdrawal Trial of Extended-Release Sodium Oxybate for Idiopathic Hypersomnia. Presented at: SLEEP Annual Meeting; June 14-17, 2026; Baltimore, MD.
2. Alkermes Announces Positive Topline Results From REVITALYZ℠ Phase 3 Study Evaluating LUMRYZ® (sodium oxybate) Extended-Release in Adults With Idiopathic Hypersomnia. News release. Alkermes. May 12, 2026. Accessed June 19, 2026. https://investor.alkermes.com/news-releases/news-release-details/alkermes-announces-positive-topline-results-revitalyzsm-phase-3
3. Dauvilliers Y, Arnulf I, Foldvary-Schaefer N, et al. Efficacy and safety of lower-sodium oxybate in adults with idiopathic hypersomnia: a phase 3 randomized withdrawal study. Lancet Neurol. 2022;21(1):53-65. doi: 10.1016/S1474-4422(21)00368-9
4. Harmony Biosciences Provides Update on the Status of the Supplemental New Drug Application for Pitolisant in Idiopathic Hypersomnia. Harmony Biosciences. News Release. February 19, 2025. Accessed: June 16, 2026. https://ir.harmonybiosciences.com/news-releases/news-release-details/harmony-biosciences-provides-update-status-supplemental-new-drug