FDA Accepts NDA for AXS-12 for the Treatment of Cataplexy in Narcolepsy

Axsome Therapeutics today announced that the US Food and Drug Administration (FDA) has accepted its New Drug Application (NDA) for reboxetine (AXS-12) for the treatment of cataplexy in narcolepsy. The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of May 1, 2027.¹

AXS-12 is a highly selective and potent norepinephrine reuptake inhibitor and cortical dopamine modulator that is thought to modulate noradrenergic activity in order to maintain muscle tone during wakefulness, and noradrenergic and cortical dopaminergic signaling to promote wakefulness and cognition function. AXS-12 has been granted FDA Orphan Drug Designation for the treatment of narcolepsy.

Phase 3 Data

AXS-12’s effectiveness is supported by data from the phase 3 SYMPHONY trial. This study evaluated the efficacy and safety of AXS-12 in patients with narcolepsy type 1 (NT1), a condition marked by excessive daytime sleepiness (EDS), cataplexy, and cognitive impairment. A total of 90 participants aged 15 to 75 years old were randomly assigned 1:1 to AXS-12 or placebo for 5 weeks, with stable concurrent modafinil/armodafinil use permitted. The primary endpoint was the ratio of weekly cataplexy attacks at week 5 vs baseline.

Baseline mean weekly cataplexy attacks were 27.7 in the AXS-12 group and 35.4 in the placebo group. AXS-12 reduced attacks by 83% compared with 66% in placebo at week 5 (rate ratio=0.49; P=0.018), with rapid effects apparent by week 1 (56% vs 31% reduction). Notably, complete cataplexy remission occurred in 33% of AXS-12 patients vs 9.5% on placebo (nominal P=.008).

Secondary endpoints—such as EDS severity (CGI-S), inadvertent naps (NSAQ), and cognitive function—also showed improvement. The investigators concluded AXS-12 met its primary endpoint with a substantial, statistically significant reduction in cataplexy, alongside improvements in EDS and cognition, suggesting effective treatment across multiple narcolepsy symptom domains with a favorable safety profile.²

Additionally, approximately 47.8% of participants in the reboxetine arm and 45.5% in the placebo arm reported having anxiety or depression (EQ-5D-5L) at baseline. Numerically, the investigators wrote that more participants improved 1 or more levels when treated with reboxetine (55.0%) than when treated with a placebo (31.6%) at the 5-week point (P = .146).

Future Directions

“We are excited by the potential of AXS-12 to provide a new, differentiated treatment option to patients living with this debilitating condition, if approved,” said Herriot Tabuteau, MD, chief executive officer of Axsome, in a press release.⁴

The FDA shared that it does not currently plan to hold an advisory committee meeting to discuss the application.

References

1. Axsome Therapeutics announces FDA acceptance of New Drug Application for AXS-12 for the treatment of cataplexy in narcolepsy. News release. 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. Thorpy M, Krahn L, Bogan R, et al. AXS-12 for the treatment of narcolepsy: topline results from the phase 3 SYMPHONY trial (PL5.007). Neurology. 2025;104(7 Suppl):1510.

3. Thorpy M, Krahn L, Bogan R, et al. Impact of AXS-12 on symptom severity and functional impairment in narcolepsy: results from the phase three SYMPHONY trial (S3.008). Neurology. 2026;106 (11 Suppl):4912.

4. Axsome Therapeutics announces FDA pre-NDA meeting minutes for AXS-12 in narcolepsy supporting NDA submission. News release. January 1, 2026. Accessed July 15, 2026. https://www.biospace.com/press-releases/axsome-therapeutics-announces-fda-pre-nda-meeting-minutes-for-axs-12-in-narcolepsy-supporting-nda-submission