J&J’s nasal antidepressant heads for FDA panel

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Johnson & Johnson’s new antidepressant esketamine comes in front of an FDA advisory committee tomorrow, hoping to end a drought in novel therapies for the disorder.

There has been a lot of debate about the likely outcome of the meeting given that not all of J&J’s studies support the intranasally administered drug, but analysts at Credit Suisse think that the FDA is “supportive of approval” based on published briefing documents.

If approved by the FDA, esketamine would become one of the first new approaches to treat refractory major depressive disorder (MDD) in the last 50 years and provide a new option for people—estimated to be in the millions worldwide—who struggle to control symptoms despite drug therapy. At the moment, only one drug is FDA-approved for treatment-resistant MDD.

J&J’s drug is designed as an add-on therapy to oral antidepressants. Last year, the company reported the results of two phase 3 studies of esketamine, including one in adults with treatment-resistant MDD, which showed that the drug was more effective than placebo in relieving symptoms. A second study in older patients aged 65 or older didn’t meet the threshold for significance, however, although J&J said it had a “clinically meaningful” impact.

In its document, the FDA says that the evidence for esketamine’s effectiveness comes primarily from “two positive phase 3 trials—the flexible-dose trial in adults younger than 65 years of age and [a] randomized withdrawal study.”

The withdrawal study—called Study 3002—did not meet its primary objective of improving depression symptoms at the primary dose of 84 mg, but the agency says data from a lower 56-mg dose can be considered as supportive, as it showed superior efficacy at the 28-day time point.

There’s no guarantee the advisory committee will follow that thinking, and the FDA acknowledges that a withdrawal study has never been used as one of the two positive efficacy trials needed to support an antidepressant approval, although it says in the briefing document that “it is not unreasonable to do so.”

J&J has picked up a pair of breakthrough therapy designations from the U.S. regulator, which is an indication of just how badly new treatment options for depression are needed. The company has previously said it expects the drug to be among a crop of new products with a $1 billion-plus sales potential.

The Credit Suisse analysts also say the documents suggest the FDA has a favorable view of esketamine’s safety profile, in particular that there isn’t a higher rate of cognitive impairment or liver injury with esketamine relative to placebo, unlike parent drug ketamine. The agency also says that none of the six deaths in the treatment arms of the studies appear to be drug-related.

Overall, the “somewhat unexpected interpretation” of that data “lays a positive foundation ahead of [the] ad comm meeting and the March 4 FDA action date,” they note.

J&J will be hoping for an easier time at the meeting than Alkermes, which was unable to convince the panel about the merits of its new-mechanism antidepressant ALKS 5461 last November. The FDA formally rejected its marketing application for the drug—a fixed-dose combination of buprenorphine and samidorphan—last week.