A FDA advisory committee has voted overwhelmingly in favor of Johnson & Johnson’s depression drug esketamine. The panel’s decision to back the ketamine-like drug despite the shortcomings of its clinical program tees J&J up to win approval for one of the most notable antidepressants in decades.
Esketamine is a form of ketamine, a drug that has developed a reputation as a novel way to treat depression over the past 20 years. The reputation is underpinned by evidence that the drug acts far faster than existing antidepressants, suggesting it could fill a gap in the toolkit physicians have to treat people with severe forms of the condition.
The advisory committee gave esketamine a big push toward real-world use this week when it voted 14-2 that the benefits of the drug outweigh the risks. The panel voted by the same margin that J&J had shown the nasal spray is effective in treatment-resistant depression.
With the panel also voting overwhelmingly in favor of the safety profile of the drug, J&J emerged from the meeting looking set to win FDA approval. J&J finds itself in that position despite the FDA and the advisory committee identifying shortcomings in the dataset it presented in support of the drug.
Two of the three pivotal trials J&J ran to assess the short-term effects of esketamine missed their primary endpoints. That meant results from one of the short-term studies—which assessed flexible doses of esketamine in people aged under 65—and data generated in a maintenance trial formed the backbone of J&J’s case for the efficacy of the drug.
While the panelists questioned whether approving a drug that failed two out of three trials would set a bad precedent, they ultimately came down on the side that the benefits of esketamine outweigh the risks in the target population.
That view is partly underpinned by the unmet need. In recent years, physicians have resorted to using ketamine off-label as there is a lack of approved, fast-acting depression drugs. With a body of evidence beyond the esketamine trials suggesting ketamine works fast—and the maintenance trial finding positive effects are sustained—J&J’s case was compelling enough to get it over the line.
The application will now advance to the FDA, which will decide whether to approve the drug. Given the frequency with which the FDA follows committee recommendations and the content of its briefing notes on esketamine, odds look good for the drug to get the green light from the agency.