Axsome reports late-stage depression trial defeat, shares wilt
Months after reporting its experimental drug cleared a late-stage study in major depressive disorder, Axsome Therapeutics unveiled data from a pivotal study in treatment-resistant depression that showed the drug failed to meet the main goal.
In general, trials testing depression drugs are notoriously tricky and prone to failure, in major part due to high rates of the placebo effect. Existing antidepressants often take weeks to kick in, and typically work only in some patients. This trial tested the therapy in patients who had failed to benefit from two or three prior treatments.
The pill AXS-05, which consists of a combination of dextromethorphan (DM) and bupropion, was tested against bupropion alone in TRD patients for 6 weeks in the late-stage 312-patient STRIDE-1 study. Data showed the company’s therapy induced a numerical reduction on the Montgomery-Åsberg depression rating scale, averaged over the 6-week treatment period, versus bupropion (p<0.001), but did not achieve statistical significance.
At week 6, AXS-05 induced a mean reduction of 11.6 on the rating scale, versus 9.4 on the bupropion arm (p=0.117).
But the company was enthusiastic about the key secondary endpoints, which were met. Data showed the Axsome therapy significantly improved symptoms over the entire six week period with mean reductions of 8.6 for AXS-05 versus 6.7 for bupropion (p=0.031). The company’s experimental therapy also started to show signs of working as early as week 1, with a reduction of 5.2 versus 3.6 on the bupropion arm (p=0.02).
The company now plans to conduct another late-stage study, where it will likely test AXS-05 against a placebo. That study is expected to kick off in the third quarter. An application to market the therapy in MDD patients is expected to be submitted in the second half of 2020.
The company has noted in the past that “a negative STRIDE-1 readout would have no impact on the NDA filing in MDD and limited impact on AXS-05’s commercial prospects, which already has a differentiated profile including new MoA, rapid onset, large effect size and favorable tolerability relative to current therapies,” SVB Leerink analysts wrote in a note last month.
But investors did not appear to be convinced. The New York-based company’s shares $AXSM tumbled about 18% at $52.12 in premarket trading.
AXS-05, which has been granted fast track status by the FDA, is also being tested as a treatment for agitation associated with Alzheimer’s and smoking cessation.
A separate application to market another experimental therapy, AXS-07, for use in acute migraine is also being prepared. In December, Axsome reported mid-stage data that showed its formulation of an old controversial Pfizer drug was effective in treating narcolepsy in a small study.