FDA Accepts Axsome NDA for AXS-12 for Cataplexy in Narcolepsy

The US Food and Drug Administration (FDA) has accepted Axsome Therapeutics’ New Drug Application for AXS-12 (reboxetine) for the treatment of cataplexy in narcolepsy, according to a company announcement.¹

The FDA set a Prescription Drug User Fee Act target action date of May 1, 2027. Axsome also stated that the agency does not currently plan to hold an advisory committee meeting to discuss the application.

AXS-12 is not approved by the FDA. The investigational agent has received FDA Orphan Drug Designation for the treatment of narcolepsy.

Narcolepsy is a chronic, serious, and debilitating neurologic condition involving dysregulation of the sleep-wake cycle. Clinical features may include excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, sleep paralysis, and disrupted nocturnal sleep.

Cataplexy is estimated to affect approximately 70% of patients with narcolepsy.² The symptom is characterized by sudden reduction or loss of muscle tone while a patient is awake and is typically triggered by strong emotions, including laughter, fear, anger, stress, or excitement.

Cataplexy can be especially disruptive because episodes may occur during routine activities and can contribute to functional limitations, injury risk, and reduced quality of life. For primary care clinicians, recognizing cataplexy is important when evaluating patients with excessive daytime sleepiness or suspected narcolepsy, particularly when patients describe emotion-triggered weakness, knee buckling, jaw slackening, head dropping, or sudden falls without loss of consciousness.

AXS-12 is a highly selective and potent norepinephrine reuptake inhibitor and cortical dopamine modulator under development for narcolepsy. The agent is thought to modulate noradrenergic activity to help maintain muscle tone during wakefulness and to modulate noradrenergic and cortical dopaminergic signaling involved in wakefulness and cognitive function, according to the company.

Narcolepsy is a lifelong disorder that can interfere with cognitive, psychological, and social functioning. The condition also is associated with increased risk of work- and driving-related accidents and has been linked to higher mortality.

For clinicians, the FDA acceptance marks a regulatory milestone but not a change in current practice. Until a decision is issued, AXS-12 remains investigational. The application will be reviewed for the proposed indication of cataplexy in narcolepsy, with the FDA’s target action date set for May 2027.

Reference

1. Axsome Therapeutics. Axsome Therapeutics announces FDA acceptance of New Drug Application for AXS-12 for the treatment of cataplexy in narcolepsy. News release. Published July 15, 2026. Accessed July 15, 2026. https://www.globenewswire.com/news-release/2026/07/15/3327580/33090/en/axsome-therapeutics-announces-fda-acceptance-of-new-drug-application-for-axs-12-for-the-treatment-of-cataplexy-in-narcolepsy.html
2. Swick TJ. Treatment paradigms for cataplexy in narcolepsy: past, present, and future. Nat Sci Sleep. 2015;7:159-69. doi:10.2147/NSS.S92140