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A Biotech's Depression Drug Returns From Dead, Setting Up Test For FDA

This article is more than 7 years old.

In January, Alkermes, a Waltham, Mass.-based biotechnology firm, announced that its experimental antidepressant, code-named ALKS 5461, had failed in two different clinical trials. Shares in the company fell from $60 to $33. Today, Alkermes announced that a third study of the drug had succeeded, leading shares to jump 43% in after-hours trading to about $60 -- essentially erasing the specter of failure.

That stock pop is obviously too much. It's good news that the drug proved effective in another study. But the big question is whether the Food and Drug Administration will be willing to approve ALKS 5461 based on this study, or whether it will demand that Alkermes conduct another clinical trial that has not yet begun yet. Alkermes will meet with the FDA to discuss its options.

Richard Pops, Alkermes' charismatic chief executive, says he thinks the chances of the FDA accepting a filing based on the data are "high" but "we’ll wait until we meet with the reviewing division." It's common for antidepressants to fail many clinical trials. The FDA's own guidance says that, because of the big placebo effects in depression studies, even effective drugs will fail half the time. But the requirement for approval has always been two successful late-stage, or phase III studies, no matter how many fail.

Alkermes currently has one success and two failures. Traditionally, that would not be enough. But Pops points out that a smaller study, conducted as a mid-stage, or phase II, study was relatively large, randomized, and successful. And he says that although they were not statistically significant, the results in the earlier studies were consistent with the successful one. He argues that despite side effects that include severe nausea, the drug is intended for people with severe depression who don't respond to other treatments, and that means its benefits outweigh its risks.

There's some precedent for this kind of thinking. Nuplazid, a treatment for Parkinson's pyschosis made by Acadia Pharmaceuticals, failed in one clinical trial but then succeeded in a second, and was approved. Other companies in the neuroscience space are taking this as a cue: Intra-Cellular Therapeutics plans to ask the FDA to approve its drug for schizophrenia even though it failed patients in a second study. But will the FDA let this become a trend?

"A lot of companies are hoping that they can take one good phase III and cobble together something from previous studies," says Harry Tracey, the president of NeuroInvestment Research. "I don’t think that’s going to work in a population where there are existing options. People who think they’re going to get Alzheimer’s cognition, or schizophrenia approvals on one phase III? I just don’t buy it."

Whether or not Alkermes can really get the FDA to accept a filing for the depression drug -- and whether the medicine will be approved -- therefore represent a test of whether the agency is really getting softer (or, in the industry's preferred phrasing, more flexible) when it comes to drug approvals. There's been speculation that it has, in part because it has been rejecting fewer medicines and in part because of specific cases like that of Sarepta Therapeutics' Exondys 51, a drug for Duchenne muscular dystrophy that the agency approved based on data showing a very small increase in a protein that is missing in the disease. But Tracy thinks that companies that are hoping the bar has been lowered are falling victim to wishful thinking. "Every time the FDA does something progressive, then they have to backtrack and regress to show that they are not just pushovers," says Tracy. "Anybody who thinks the fDA is just opening the gates up and that more standards will be lax is just kidding themselves. It’s always cyclical."

Still, Tracy says (and I agree) more power to Alkermes for trying. And maybe the data are so consistent that they will win the day. Patients with severe depression could use some options. But Tracy, who has followed neuroscience drugs for 21 years, can't remember a case where the FDA let a company count a phase II as a phase III. "It would be an interesting test case to see if the flexibility shown by the FDA is not just a temporary blip," he says. But investors should remember that, especially with an election about to happen, the political climate for the FDA can change very, very fast.