The Food and Drug Administration (FDA) has given AXS-05 (dextromethorphan bupropion; Axsome Therapeutics) priority review for the treatment of major depression (MDD).
AXS-05 is composed of dextromethorphan, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, and bupropion, a norepinephrine and dopamine reuptake inhibitor that is used to increase the bioavailability of dextromethorphan. The NDA is supported by data from the randomized, double-blind, controlled phase 3 studies GEMINI (ClinicalTrials.gov: NCT04019704) and phase 2 ASCEND studies (ClinicalTrials.gov: NCT03595579) in which AXS-05 was performed in patients with MDD was rated.
The GEMINI study included 327 adults who met DSM-5 criteria with confirmed moderate to severe MDD. Patients were randomly given 1: 1 to receive either AXS-05 tablet or placebo once daily for the first 3 days, then twice daily for a total of 6 weeks.
The results of the GEMINI study showed that treatment with AXS-05 resulted in a statistically significant decrease in the overall Montgomery-Åsberg Depression Rating Scale (MADRS) score compared to placebo at week 6 (16.6 points for AXS-05 versus 11 , 9 points for placebo; P = 0.002). In addition, at week 6, AXS-05 was associated with a significant improvement in the Clinical Global Impression of Improvement (CGI-I) scale compared to placebo (P = 0.016). Patients treated with AXS-05 also reported rapid improvement in depressive symptoms from week 1 and at any time thereafter.
In the ASCEND study, 80 patients with confirmed moderate to severe MDD were randomly assigned to receive either AXS-05 or bupropion twice daily for 6 weeks. Results indicated that AXS-05 met the primary endpoint, showing a statistically significant mean mean reduction in total MADRS of 13.7 points versus 8.8 points with bupropion from baseline (P <0.001).
For safety reasons, dizziness, nausea, headache, diarrhea, drowsiness and dry mouth were the most commonly reported adverse events. In addition, it was found that treatment with AXS-05 was not associated with psychotomimetic effects or weight gain.
A target date of the Prescription Drug User Fee Act (PDUFA) of August 22, 2021 has been set for this application.
“We are pleased with the FDA’s acceptance and priority review of our NDA for AXS-05 in major depression, and look forward to continuing to work closely with the FDA throughout the review process,” said Herriot Tabuteau, MD, CEO of Axsome . “If AXS-05 is approved, it will be an important new treatment option for the many Americans living with depression.”
The company is also investigating AXS-05 in the Phase 3 STRIDE-1 study (ClinicalTrials.gov: NCT02741791) as a potential therapy for treatment-resistant depression and in the ADVANCE-1 study (ClinicalTrials.gov: NCT03226522) in patients with Alzheimer’s disease -Disease agitation.
- Axsome Therapeutics Announces FDA Approval and Priority Review of New Drug Application for AXS-05 for the Treatment of Depression. [press release]. New York, NY: Axsome Therapeutics, Inc; April 26, 2021.
- Axsome Therapeutics Announces New Data From GEMINI Phase 3 Study Of AXS-05 Showing Rapid And Significant Improvement In Major Depression Patient-Reported Outcomes. [press release]. New York, NY: Axsome Therapeutics, Inc; September 14, 2020.
- Axsome Therapeutics Completes Successful FDA Pre-NDA Meeting for AXS-05 for the Treatment of Depression. [press release]. New York, NY: Axsome Therapeutics, Inc; July 13, 2020.
This article originally appeared on MPR