Publication of RESTORE data highlighting challenges with twice-nightly oxybates and strong patient preference for once-nightly Lumryz dosing (sodium oxybate) extended-release oral suspension – Avadel Pharma

Avadel Pharmaceuticals plc , announced the publication of final data from the RESTORE open-label/switch study, demonstrating that people with narcolepsy prefer once-at-bedtime Lumryz versus a twice-nightly immediate-release oxybate treatment option.

The FDA approved Lumryz in 2023 as the first and only once-nightly oxybate, which marked a significant milestone for people with narcolepsy, as twice-nightly oxybates were the only other oxybate options available for more than 20 years. The paper, titled “RESTORE: Once-Nightly Oxybate Dosing Preference and Nocturnal Experience With Twice-Nightly Oxybates,” was published online in Sleep Medicine: X. Initial and end-of-study survey data from RESTORE were previously presented in April 2022 at the American Academy of Neurology Annual Meeting and in June 2024 at SLEEP 2024.

“Twice-nightly oxybates can present significant treatment burdens and adherence concerns given the required middle-of-the-night awakening for a second dose. RESTORE study participants overwhelmingly preferred the once-nightly dosing regimen of Lumryz over twice-nightly oxybates. RESTORE further highlighted the inconvenience with the middle-of-the-night dose, as well as the associated grogginess and unsteadiness the following morning if the dose was taken late, and the worsening of symptoms when the dose was missed,” said Asim Roy, M.D., co-author of the paper and RESTORE investigator, and Medical Director of the Ohio Sleep Medicine Institute.

“With Lumryz, the majority of switch participants who participated in the survey reported improvements in their ability to get through the day without falling asleep, being better able to sleep through the night, and accomplish more in professional and social settings.”

As part of the multicenter, open-label Phase III RESTORE extension/switch study, participants with narcolepsy type 1 or 2 who switched from a twice-nightly oxybate to once-nightly Lumryz completed a nocturnal adverse events questionnaire at baseline, a patient preference questionnaire after three months of taking Lumryz, and an end-of-study questionnaire.

Results; Of the 129 switch participants who completed the nocturnal adverse events questionnaire at baseline : i. 69% reported missing their second oxybate dose, and of those participants, 80% felt that control of their symptoms was worse the next day compared to days after which they had taken both doses as prescribed.. ii. More than half (51%) of the 51 participants who took their second nightly oxybate dose more than four hours after the first dose reported feeling somewhat to extremely groggy or unsteady the next morning. iii. 92% reported getting out of bed after taking their second dose of oxybate, with 7.5% of those reporting falling after waking up for the second dose, and 4.2% reporting injuries. iv . 23% of participants stated they required another person to wake with them in the middle of the night to ensure they took the second dose of their twice-nightly oxybate.

Of the 98 switch participants who completed the patient preference questionnaire:, 94% preferred once-at-bedtime LUMRYZ to twice-nightly oxybate dosing.

Of the 68 switch participants who completed the end-of-study questionnaire :. i. 79% were very satisfied with Lumryz compared to other narcolepsy treatments they had previously taken. ii. 93% would recommend Lumryz to a family member or friend with narcolepsy. iii. 91% said they were better able to sleep through the night since starting treatment with Lumryz. iv. 91% said they were better able to follow the recommended medication schedule of Lumryz than their previous oxybate.

“The RESTORE study, which was conducted for more than three years, allowed investigators switching participants from twice-nightly, first-generation oxybates to understand the myriad challenges associated with chronically taking a middle-of-the-night dose of medication. Nearly 1 out of 4 switch participants reported needing someone else to wake up with them to take the middle-of-the-night dose. Once-at-bedtime Lumryz avoids the dosing burden of a twice-nightly oxybate, which as RESTORE affirms, is experienced in multiple negative aspects for patients, which can be avoided with Lumryz. Not surprisingly, among those switching, more than nine in 10 would recommend Lumryz to a family member or friend with narcolepsy,” said Jennifer Gudeman, Pharm.D., Senior Vice President, Medical and Clinical Affairs of Avadel.

“Data from RESTORE demonstrate Lumryz was well tolerated, with a low rate of discontinuation due to adverse events, and further confirmed the long-term safety and tolerability of this innovative treatment option.”-

The FDA approval of Lumryz was supported by results from REST-ON, a randomized, double-blind, placebo-controlled, pivotal Phase III trial in adults with narcolepsy. Lumryz demonstrated statistically significant and clinically meaningful improvements in the three co-primary endpoints: EDS, clinicians’ overall assessment of patients’ functioning (CGI-I), and cataplexy attacks, for all three evaluated doses when compared to placebo.

See- RESTORE: “Once-nightly oxybate dosing preference and nocturnal experience with twice-nightly oxybate”/ lAsim Roy , Thomas Sternb, John Harsh , J. Douglas Hudson , Akinyemi O. Ajayi, Bruce C. Corserf, Emmanuel Mignot , Adrian Santamaria , Anne Marie Morse , Brian Abaluck , et al.,-Sleep Medicine: X.Volume 8, 15 December 2024, 100122.