After Axsome's migraine med rejection, phase 3 data keep hope alive for depression drug

Positive phase 3 trial results have maintained momentum for Axsome Therapeutics' convoluted depression drug application, less than a month after the FDA rejected the company's migraine treatment.

The GEMINI trial found that AXS-05, a combination of the active ingredient of GlaxoSmithKline’s Wellbutrin and a cough medicine, demonstrated “rapid, substantial and statistically significant antidepressant efficacy” in patients with major depressive disorder (MDD) compared to placebo, according to the results published in The Journal of Clinical Psychiatry.

The depression drug has hardly had a straightforward run to approval, with Axsome agreeing in April to a set of postmarketing conditions proposed by the FDA, with the aim of getting back on track after the agency identified deficiencies in the application for AXS-05 last year.

With no details of the conditions made public at the time, analysts and investors were left guessing at what was agreed to. But one thing the regulatory filing did say is that Axsome anticipated the FDA would act on its application in the second quarter of 2022.

With that deadline rapidly approaching, the data gives some insight into why Axsome is confident about its application. The GEMINI trial consisted of 327 MDD patients receiving either AXS-05 or a placebo for six weeks, with the primary endpoint of baseline changes in the Montgomery-Åsberg Depression Rating Scale (MADRS) score to week six significantly greater for AXS-05 patients than those taking the placebo. As well as the drug's effect being noted from the first week of treatment, the majority of secondary outcomes also favored AXS-05, according to the study.

Patients tolerated AXS-05 well, with the most common adverse events reported being dizziness, nausea, headache, diarrhea, somnolence and dry mouth, Axsome said.

The latest readout follows another set of positive data from the ASCEND phase 2 clinical trial of AXS-05, published May 18 in The American Journal of Psychiatry. AXS-05 is also being tested as a therapy for Alzheimer’s disease agitation and smoking cessation.

"These studies demonstrate a consistent efficacy profile for AXS-05 and form the basis of our NDA for the treatment of depression," said Axsome CEO Herriot Tabuteau, M.D., in a statement.

Axsome is in need of some good news this month, mere weeks after the FDA rejected its migraine treatment AXS-07 over unresolved issues with chemistry, manufacturing and controls. Axsome noted at the time that regulators did not flag any issues regarding the company’s clinical or safety data and pledged to update the timing on resubmitting a new drug application after talking with the FDA.