A post-hoc analysis confirmed the efficacy of Lumryz in study participants who were and were not using a stable dose of an alerting agent.

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Summary: A post-hoc analysis of the phase 3 REST-ON trial demonstrated that Lumryz (sodium oxybate) improves narcolepsy symptoms, including wakefulness, cataplexy episodes, and daytime sleepiness, regardless of whether patients were also using alerting medications. Both groups—those taking and not taking alerting agents—experienced clinically meaningful improvements. The study highlights Lumryz’s potential as an effective treatment for narcolepsy, even in patients who are already using stimulant or wake-promoting drugs.

Three Key Takeaways:

1. Efficacy Regardless of Other Medications: Lumryz improved narcolepsy symptoms, including daytime sleepiness and cataplexy, regardless of whether patients were using alerting agents like stimulants.
2. Symptom Improvement: Patients saw meaningful improvements in wakefulness, overall condition, and number of weekly cataplexy episodes, with significant changes in the Maintenance of Wakefulness Test and Epworth Sleepiness Scale scores.
3. Potential as Monotherapy: For 37% of patients not taking alerting agents, the analysis suggests that Lumryz monotherapy may be sufficient to manage narcolepsy symptoms effectively.

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Avadel Pharmaceuticals plc announced the publication of results of a post-hoc analysis from the completed pivotal phase 3 REST-ON clinical trial, which demonstrated clinically significant improvements from baseline in wakefulness, overall condition, number of weekly cataplexy episodes, and excessive daytime sleepiness in patients taking Lumryz (sodium oxybate) compared to those taking placebo, regardless of concomitant use of alerting agents. 

The paper was published online in Sleep Medicine.

“Treatment of narcolepsy often requires multiple medicines to adequately control symptoms. Alerting agents, including stimulants and wake-promoting agents, are often the first treatment prescribed for narcolepsy,” says Richard K. Bogan, MD, FCCP, FAASM, associate clinical professor at the University of South Carolina School of Medicine and Medical University of South Carolina in Charleston, in a release. 

Bogan continues, “In REST-ON, subjects in the alerting agent subgroup were also pathologically sleepy at baseline and could only remain awake for approximately five minutes during the Maintenance of Wakefulness Test (MWT). Both subgroups had marked improvement on daytime sleepiness with once-at-bedtime Lumryz. While this would be expected clinically, this type of post-hoc analysis has not been previously undertaken to evaluate the addition of an oxybate to a stable alerting agent regimen.”

The randomized, double-blind, placebo-controlled, pivotal phase 3 REST-ON trial evaluated once-at-bedtime Lumryz in adults with narcolepsy. Primary endpoints included change from baseline in mean sleep latency on the MWT, Clinical Global Impression-Improvement (CGI-I) rating, and number of weekly cataplexy episodes. Secondary endpoint was change from baseline in the Epworth Sleepiness Scale (ESS) score.

Dauvilliers et al evaluated the efficacy of Lumryz on these endpoints in participants with narcolepsy who were taking and not taking alerting agents (modafinil, armodafinil, various amphetamines, dexamphetamine sulfate, and methylphenidate hydrochloride). A total of 119 study participants (63%) were taking alerting agents and 71 (37%) were not.

Study Results

Results of the post-hoc analysis:

• Significant improvements with Lumryz at all doses were seen versus placebo for MWT, CGI-I and number of weekly cataplexy episodes (p<0.05) regardless of alerting agent use, which were also clinically meaningful.
• Similarly, ESS was significantly improved with Lumryz at all doses versus placebo in the group taking alerting agents (p<0.05), with significant improvements for the non-alerting agent group at the 7.5 g and 9 g dose, and directional improvement at Week 3 with the 6 g dose.

“It is important for clinicians and people with narcolepsy to recognize that alerting agents alone may not be sufficient to treat excessive daytime sleepiness. As with other oxybates trials, a high proportion of subjects were on stable doses of alerting agents, yet still qualified for study entry based upon pathological sleepiness.

“These data should help initiate discussions between patients and clinicians to assess whether an alerting agent regimen alone is sufficiently managing their narcolepsy. Additionally, for the 37% of participants not on alerting agents, these results show that Lumryz monotherapy may be sufficient to manage narcolepsy symptoms,” says Jennifer Gudeman, PharmD, senior vice president, of medical and clinical affairs at Avadel, in a release. 

Lumryz was approved by the US Food and Drug Administration on May 1, 2023, as the first and only once-at-bedtime treatment for cataplexy or excessive daytime sleepiness in adults with narcolepsy.

Photo caption: Lumryz

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