November 3, 2016
By Steve Zisson, BioSpace.com Senior Editor
Alkermes’ depression drug candidate may have a better than expected chance for U.S. Food and Drug Administration (FDA) approval even though the treatment did no better than placebo in its first two pivotal clinical trials earlier this year.
Alkermes ’ case for approval was boosted two weeks ago, and its shares rocketed up, after the company announced its experimental drug ALKS-5461 significantly reduced symptoms in patients suffering from major depressive disorder who were not helped by standard treatments. ALKS-5461 is being developed as an add-on treatment for patients with major depression. ALKS-5461 is actually a drug combination including buprenorphine, which is a kappa-opioid receptor (KOR) antagonist, and samidorphan, a mu-opioid (MOR) antagonist. Together, these two drugs are designed to provide the antidepressant KOR effects of buprenorphine but also tamp down its addictive potential with the MOR activity of samidorphan.
Back in January the news wasn’t so rosy for Alkermes, which reported then that two of its clinical trials studying ALKS 5461 failed to meet their primary endpoints, and the company’s shares cratered. At the time of these failures, Alkermes said the drug still had potential in its Forward-5 Phase III study.
According to Endpoints, the company did a retrospective analysis and reworked its argument for the drug’s approval soon after the bad news from its first two pivotal trials. Researchers added new patients and revamped its statistical analysis for the Forward-5 trial. The company told Endpoints its second Phase III study failed because it hinged on depression scores at a particular time. In the successful and latest trial, researchers used an average depression score over weeks instead of one point in time, Endpoints noted.
The latest data from pivotal Phase III Forward 5 clinical trial showed that a 2 mg dose of ALKS 5461, a once-daily, oral treatment, reduced depression scores compared to placebo as measured by the Montgomery–Asberg Depression Rating Scale. The 1 mg dose of ALKS 5461 showed improvement in depressive symptoms in the study, but was not significant enough compared with from placebo, the company said.
Following the latest trial’s positive results, the company plans to meet with the FDA to determine the steps the company needs to make as it seeks regulatory approval of ALKS-5461.
Alkermes still faces a number of hurdles for approval. The company hadn’t received any feedback from the FDA about the changes its researchers made, according to Endpoints, and using a retrospective analysis to gain approval is typically a stretch. Only going one for three on positive results for its trials usually adds up to the FDA rejecting it. Typically, the FDA looks for two out of three trials to return positive clinical trial results for a drug to be approved.
But given these trial results, ALKS-5461 will likely help some patients, so the FDA may just might want to give psychiatrists another drug to prescribe because major depression is such an intractable disease.Many patients try and fail numerous antidepressants before hitting on one that works—if they ever find one that relives their suffering. A growing list of already marketed antidepressants have been criticized as working no better than placebo.
Pharma and biotech companies have been largely giving up on finding new antidepressants because the science of the brain is so difficult and the path to approval is torturous.Alkermes is not giving up.
