Axsome Presents Positive Phase 3 Data for AXS-12 in Narcolepsy at SLEEP 2025

Axsome Therapeutics presented several phase 3 data at SLEEP 2025, the 39th annual meeting of the Associated Professional Sleep Societies, on Wednesday, June 11 in Washington, Seattle.1

Phase 3 data presented included topline results from ENCORE, a phase 3 open-label extension and randomized-withdrawal trial of AXS-12 in narcolepsy, and SYMPHONY, a phase 3 trial examining AXS-12 on symptom severity and functional impairment in narcolepsy.

“The results of the Phase 3 ENCORE study, coupled with the results of the phase 3 SYMPHONY study, support the positive therapeutic impact of AXS-12 for narcolepsy with cataplexy,” wrote the team, led by Richard K. Bogan, from the Medical University of South Carolina on their poster.2

AXS-12 (reboxetine), a highly selective and potent norepinephrine reuptake inhibitor and cortical dopamine modulator, is under development for the treatment of narcolepsy. The US Food and Drug Administration (FDA) granted AXS-12 the Orphan Drug Designation for treating narcolepsy.

This drug is believed to modulate noradrenergic activity to maintain tone during wakefulness. The noradrenergic and cortical dopamine signaling promotes wakefulness and cognition.

“Based on the concurrent improvements observed on cataplexy, severity of excessive daytime sleepiness, cognition, and overall function, I believe AXS-12 represents a meaningful enhancement to the treatment armamentarium for narcolepsy patients and clinicians and will be a welcome treatment option in our fight against the devastating impact of narcolepsy on patients and their loved ones,” said Michael Thorpy, MD, director of the Sleep-Wake Disorders Center at the Montefiore Medical Center and Professor of Neurology at Albert Einstein College of Medicine, in a statement published in March 2024 regarding SYMPHONY.3

Axsome Therapeutics announced at the meeting that after 24 weeks of open-label AXS-12 label use, the mean weekly frequency of cataplexy attacks was 4.2 for participants randomized to AXS-12 vs 6.9 for those randomized to placebo for the subsequent 3-week double-blind randomized-withdrawal period.2 From the start to end of the 3-week double-blind randomized-withdrawal period, participants on AXS-12 had a lower increase in least squares mean increase of weekly cataplexy than those on placebo (1.32 vs 10.29; P = .017).

The company also presented trials on solriamfetol, including the real-world SURWEY study evaluating solriamfetol effects on neuropsychological outcomes in patients with obstructive sleep apnea (OSA) and a trial studying the real-world use of solriamfetol for excessive daytime sleepiness in OSA.4

Solriafetol, a dopamine and norepinephrine reuptake inhibitor, TAAR1 agonist, and 5-HT1A agonist, is being developed for the treatment of ADHD, major depressive disorder (MDD), binge eating disorder, and excessive sleepiness associated with shift work disorder.

In the SURWEY trial, Test of Attentional Performance scores improved by 11.4% after 3 months of solfriamfetol, BC-CC scores improved by a mean of 40.8%, and Epworth Sleepiness Scale scores improved by 4.7±2.7 (all P < .01).

“These real-world results show that solriamfetol not only reduces EDS in patients with OSA but also has the potential to partially reduce OSA-associated cognitive impairment,” wrote the team, led by Yaroslav Winter, MD, from the Mainz Comprehensive Epilepsy and Sleep Medicine Center at Johannes Gutenberg-University, in their abstract. “This effect was not associated with changes in [excessive daytime sleepiness].”

References

1. Axsome Therapeutics Showcases Innovation in Sleep Medicine with Multiple Presentations for AXS-12 and Solriamfetol at SLEEP 2025. Axsome Therapeutics. June 11, 2025. https://axsometherapeuticsinc.gcs-web.com/news-releases/news-release-details/axsome-therapeutics-showcases-innovation-sleep-medicine-multiple. Accessed June 11, 2025.

2. Borgan R, Thorpy M, Krahn L. ENCORE: TOPLINE RESULTS OF A PHASE 3 OPENLABEL EXTENSION AND RANDOMIZED-WITHDRAWAL TRIAL OF AXS-12 IN NARCOLEPSY. Abstract presented at SLEEP 2025 in Seattle, Washington from June 8 – 11, 2025.

3. Derman, C. Axsome Therapeutics Announces New SYMPHONY, CRESCENDO Data in Narcolepsy. HCPLive. March 25, 2024. https://www.hcplive.com/view/axsome-therapeutics-announces-new-symphony-crescendo-data-narcolepsy. Accessed June 11, 2025.

4. Winter Y, Eglit, G, Floam S. EFFECTS OF SOLRIAMFETOL ON NEUROPSYCHOLOGICAL OUTCOMES IN PATIENTS WITH OBSTRUCTIVE SLEEP APNEA IN THE REALWORLD SURWEY STUDY. Abstract presented at SLEEP 2025 in Seattle, Washington from June 8 – 11, 2025.