FDA rejects Alkermes antidepressant drug ALKS 5461

The company’s shares were down more than 4 percent in Monday morning trading after the agency’s decision, which itself followed a negative AdCom vote in November.

The Food and Drug Administration turned down a drug for depression that had previously received a negative opinion from a panel of experts the agency convened to review the developer’s application.

Dublin-based Alkermes said Friday that it received a complete response letter from the agency for its drug, ALKS 5461, developed as an adjunctive treatment for major depressive disorder. The agency said it would need more clinical data to provide “substantial evidence” for the drug’s efficacy. The company said it plans to meet with the FDA to discuss the CRL’s contents and potential next steps for the drug. However, the request for additional data likely means the company would have to conduct another clinical trial.

Shares of Alkermes on the Nasdaq were down 4.2 percent in mid-morning trading Monday. ALKS 5461 is a combination of the opioid buprenorphine and samidorphan, an opioid antagonist.

In November, the FDA’s Psychopharmacologic Drugs Advisory Committee, or PDAC, voted 21-to-2 that the risk-benefit profile of ALKS 5461 was not sufficient to support its approval. While the FDA is not bound by AdCom votes when it decides whether or not to approve a drug, it usually follows the panels’ advice.

A briefing document released the week of the AdCom vote had already cast doubt on the panel’s sentiments toward the drug. Concerns panelists raised included its safety and efficacy, while they also criticized the use of an abbreviated scoring system for measuring efficacy.

According to the document, while the PDAC agreed with Alkermes that the drug’s inclusion of samidorphan meant it would carry fewer opioid effects than if it only included buprenorphine, “there remains some evidence of a mild opiate effect (including mild withdrawal effects) from the trials.” Phase III data on the drug published that week showed “minimal evidence of abuse, and no evidence of dependence or opioid withdrawal by [adverse events] or objective measures.”

There were also disagreements between the FDA and the company about the trial’s design and how it measured efficacy. The agency had only accepted one Phase III trial – FORWARD-5 – for consideration, given that the other two Phase III trials Alkermes submitted were negative, and a Phase II trial was only designed for proof of concept, rather than efficacy.

Photo: Streeter Lecka, Getty Images