Axsome advances NDA filing for narcolepsy drug after positive Phase 3 results

Axsome Therapeutics has announced that its narcolepsy medication, AXS-12, successfully achieved the primary endpoint in its Phase 3 ENCORE trial. The trial demonstrated a significant reduction in the frequency of cataplexy episodes among patients with narcolepsy when compared to a placebo.

Chief Executive Officer Herriot Tabuteau indicated that the company plans to swiftly advance towards filing a New Drug Application (NDA) for AXS-12. The company intends to request a pre-NDA meeting with the U.S. Food and Drug Administration (FDA).

Cataplexy, a common symptom of narcolepsy, is characterized by sudden, temporary muscle weakness triggered by strong emotions such as laughter or anger. This condition can result in localized muscle weakness, such as facial drooping, or more widespread muscle weakness, leading to falls.

In the ENCORE trial, 68 patients were administered AXS-12 for six months before being randomly assigned to two groups. One group continued with AXS-12, while the other group received a placebo for three weeks. The results showed that patients on the placebo experienced an increase of 10.29 cataplexy attacks per week, whereas those on AXS-12 had an increase of only 1.32 attacks per week (p=0.017).

Michael Thorpy, a professor of neurology at the Albert Einstein College of Medicine, emphasized that AXS-12 "has the potential to rapidly and durably ameliorate one of the most debilitating symptoms for patients."

Beyond cataplexy, the trial indicated improvements in other narcolepsy symptoms among patients taking AXS-12. Specifically, 55% of patients reported improved cognition after one month, and this figure rose to 59% after six months. Additionally, improvements in concentration were reported by 67% of patients at one month and 70% at six months.

The development of AXS-12 faced a minor delay in 2023 due to challenges in achieving adequate enrollment for the trial. Axsome Therapeutics acquired AXS-12 in 2020 by licensing clinical and nonclinical data from Pfizer for reboxetine, the drug’s active ingredient.

The trial did not reveal any new safety concerns for AXS-12. The most frequently reported adverse events were nausea and tachycardia. Over the initial six-month treatment period, 17.6% of patients discontinued treatment due to adverse events, but no discontinuations occurred during the randomized three-week portion.

Following the announcement of the trial results, Axsome’s stock ($AXSM) experienced a slight increase of just over 1% on Tuesday. Analysts from Mizuho noted that while the trial data itself may not be highly significant, AXS-12 is perceived as a minor market opportunity with projected peak sales of approximately $140 million. However, the ENCORE trial provides the essential long-term data necessary for Axsome to proceed with filing its NDA.