New York-based Axsome Therapeutics (Nasdaq: AXSM) said the US FDA has accepted for review its New Drug Application for AXS-12 (reboxetine) for cataplexy in patients with narcolepsy, assigning a PDUFA target action date of May 1, 2027. The agency also indicated it does not currently plan to convene an advisory committee meeting.
Cataplexy, the sudden loss of muscle tone triggered by strong emotion, affects an estimated 70% of narcolepsy patients and is thought to stem from disrupted noradrenergic signaling that normally maintains muscle tone during wakefulness. AXS-12 is designed to inhibit norepinephrine reuptake while also modulating cortical dopaminergic activity, an approach intended to address cataplexy through a distinct daytime, oral mechanism rather than the nighttime sedative dosing used by existing options.
Cataplexy treatment FDA approvals to date have centered on sodium oxybate formulations, including Jazz Pharmaceuticals' Xyrem and Xywav and Avadel Pharmaceuticals' Lumryz, all of which are Schedule III controlled substances distributed through a restricted REMS program and dosed at bedtime, often twice nightly. Harmony Biosciences' pitolisant (Wakix), an H3 receptor antagonist, offers a non-scheduled, once-daily oral alternative but has generally shown more modest anti-cataplectic effects than oxybates in cross-trial comparisons. AXS-12, if it eventually receives AXS-12 FDA approval, would introduce a non-scheduled, orally dosed option intended for daytime use, positioning it differently from both drug classes rather than directly replicating either.
The NDA follows Axsome's presentation of Phase III open-label extension and randomized-withdrawal data from the ENCORE trial of AXS-12 at SLEEP 2026, the annual meeting of the Associated Professional Sleep Societies, where investigators reported cognitive and functional outcomes in patients with narcolepsy and cataplexy. The company has not disclosed primary efficacy or safety results from the pivotal program in this filing announcement.