Axsome's experimental drug AXS-05 hits main goal of late-stage major depressive disorder study

Shares in Axsome Therapeutics jumped as much as 82% on Monday after the company reported that a Phase III study of the experimental drug AXS-05 in adults with moderate-to-severe major depressive disorder (MDD) met its primary endpoint. CEO Herriot Tabuteau remarked that given "the previously completed [mid-stage] ASCEND study, the efficacy of AXS-05 in MDD has now been demonstrated in two positive well-controlled trials." The company expects to file the NMDA receptor antagonist for approval with the FDA in the second half of 2020.

In the latest trial, called GEMINI, 327 adults with confirmed moderate-to-severe MDD were randomised to treatment with either AXS-05, which is an oral fixed-dose combination of dextromethorphan and bupropion, or placebo once daily for the first three days, and then twice daily thereafter, for a total of six weeks. The study's main goal was change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at the six-week mark, while secondary endpoints included MADRS change at weeks one and two, remission, response, Clinical Global Impression-Improvement (CGI-I), Clinical Global Impression-Severity (CGI-S), Patient Global Impression-Improvement (PGI-I), MADRS-6 and Sheehan Disability Scale (SDS).

Axsome said AXS-05 "rapidly and significantly" improved depression symptoms, with mean reductions in MADRS score of 16.6 points at week six, compared to 11.9 points for placebo. The company noted that statistical significance on the MADRS total score was demonstrated by the first week and at all time points thereafter. Rates of remission, defined as a MADRS total score of 10 or below, were also significantly greater for AXS-05 compared to placebo from week two onwards, being achieved by 39.5% of patients given the drug, versus 17.3% for placebo at week six.

In addition, Axome reported that response, as measured by an improvement of at least 50% in the MADRS total score, was observed at week six in 54% of patients in the AXS-05 group, compared to 34% for placebo. Meanwhile, all secondary endpoints improved in favour of AXS-05 and achieved significance after six weeks. The company also noted that AXS-05 was well tolerated in the trial, with discontinuation rates due to adverse events being low in both groups, while treatment with AXS-05 was not associated with psychotomimetic effects or weight gain.

"We are very pleased with the compelling results…which demonstrate the potential for AXS-05 to provide significant benefits to patients living with depression, based on observed rapid and sustained antidepressant effects, resulting from its potentially first-in-class, oral NMDA receptor antagonist and multimodal mechanism of action," said Tabuteau.

Commenting on the results, Suntrust Robinson Humphrey analyst Joon Lee noted that he was impressed with the drug's magnitude and rapidity of effect, as well as the benefit seen across several secondary goals. "We believe AXS-05 is well-positioned for commercial success in MDD and is likely be the go-to drug for those who don't respond to first-line antidepressants," the analyst added.

Aside from MDD, for which it has an FDA breakthrough therapy designation, AXS-05 is also being tested in other central nervous system disorders. The drug is currently being evaluated in the Phase III STRIDE-1 trial of patients with treatment-resistant depression, as well as in the ADVANCE-1 study in patients with Alzheimer's disease agitation.

Earlier this month, shares in Sage Therapeutics sunk after results from the late-stage MOUNTAIN trial showed that its experimental drug SAGE-217 failed to significantly improve symptoms as measured by the Hamilton Rating Scale for Depression (HAM-D) in patients with MDD. Also known as zuranolone, Sage's drug acts as a positive allosteric modulator of GABA type A receptors. For further insight, see KOL Views Results: MOUNTAIN is more speed bump than impassable impediment, says leading psychiatrist.

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