Axsome Therapeutics Announces Positive Phase 3 Results for Narcolepsy Drug AXS-12

Axsome Therapeutics' Phase 3 SYMPHONY trial revealed positive outcomes for AXS-12 (reboxetine) in reducing narcolepsy symptoms. AXS-12 significantly decreased cataplexy attacks by 83% compared to placebo (66%) and achieved remission in 33% of patients. Improvements were also observed in excessive daytime sleepiness severity and cognitive function. AXS-12 demonstrated a favorable safety profile with common mild to moderate adverse events. The drug's Orphan Drug Designation and patent protection until 2039 provide potential exclusivity upon FDA approval.

Axsome Therapeutics Reports Positive Phase 3 Results for Narcolepsy Drug AXS-12

NEW YORK, March 8, 2023 - Axsome Therapeutics, Inc. (NASDAQ: AXSM), a biopharmaceutical company focused on developing and commercializing novel therapies for central nervous system disorders, today announced positive top-line results from its pivotal Phase 3 SYMPHONY trial evaluating AXS-12 (reboxetine) for the treatment of narcolepsy.

The randomized, double-blind, placebo-controlled SYMPHONY trial enrolled 90 patients with narcolepsy. Participants received either AXS-12 or placebo for five weeks. The primary endpoint was the change from baseline in weekly cataplexy attacks, a sudden loss of muscle tone triggered by strong emotions that is a hallmark symptom of narcolepsy.

AXS-12 met the primary endpoint, demonstrating a statistically significant reduction in weekly cataplexy attacks at Week 5 compared to placebo. The mean reduction from baseline was 83% in the AXS-12 group versus 66% in the placebo group (p<0.001). Additionally, 33% of patients treated with AXS-12 achieved complete remission of cataplexy by Week 5, compared to 9.5% of patients receiving placebo (p=0.003).

Improvements were also observed in excessive daytime sleepiness (EDS), another core symptom of narcolepsy. Patients treated with AXS-12 experienced a mean reduction of 1.8 points on the Clinician Global Impression of Severity scale for EDS, compared to a 0.9-point reduction in the placebo group (p<0.001). Cognitive function, as measured by the Cognitive Function Items of the Functional Outcomes of Sleep Questionnaire, also improved significantly with AXS-12 treatment (p<0.001).

The safety profile of AXS-12 was favorable. The most common adverse events were dry mouth, nausea, and constipation, which were generally mild to moderate in severity. The trial reported low rates of discontinuation due to adverse events.

"These positive Phase 3 results demonstrate the potential of AXS-12 to significantly reduce cataplexy attacks and improve EDS in patients with narcolepsy," said Herriot Tabuteau, M.D., Chief Executive Officer of Axsome Therapeutics. "The rapid and substantial reduction of cataplexy events is particularly encouraging, as this symptom can be debilitating and often persists despite existing treatments."

AXS-12 has been granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) for the treatment of narcolepsy. The company has also filed for a New Drug Application (NDA) for AXS-12 and expects to receive a decision from the FDA in the second half of 2023. If approved, AXS-12 would be the first new treatment for narcolepsy in over a decade.

Axsome Therapeutics plans to present detailed results from the SYMPHONY trial at upcoming scientific meetings. The company is also conducting an ongoing open-label safety extension trial of AXS-12 to further evaluate the long-term safety and efficacy of the drug.

AXS-12 is protected by issued patents until at least 2039, providing the potential for seven years of marketing exclusivity in the United States upon FDA approval.

About Narcolepsy

Narcolepsy is a chronic neurological disorder characterized by excessive daytime sleepiness (EDS), cataplexy, and other sleep-related disturbances. EDS is a disabling symptom that can lead to difficulty concentrating, memory problems, and impaired performance at work or school. Cataplexy is a sudden loss of muscle tone that can be triggered by strong emotions, such as laughter or anger. Narcolepsy can have a significant impact on the quality of life of affected individuals and their families.

About Axsome Therapeutics

Axsome Therapeutics is a biopharmaceutical company dedicated to developing and commercializing novel therapies for central nervous system disorders. The company's pipeline includes several product candidates in clinical development for the treatment of depression, migraine, narcolepsy, and Alzheimer's disease. Axsome Therapeutics is headquartered in New York City.

Forward-Looking Statements

This press release contains forward-looking statements that involve substantial risks and uncertainties. These statements are based on current expectations and assumptions that are subject to change. Actual results could differ materially from those projected in any forward-looking statements due to various factors, including the uncertainties inherent in clinical development and regulatory approval processes. Axsome Therapeutics undertakes no obligation to update or revise any forward-looking statements.