J&J has taken another big step forward in its quest to bring home a blockbuster approval for its nasal spray formulation of ketamine as a new remedy for major depression.
Just weeks after the pharma giant reported that esketamine had essentially aced short-term pivotal studies, researchers are back with evidence of its long-term efficacy. But they will likely face careful scrutiny over the substantial side effects spurred by the therapy, including a set of serious adverse events reported in the lengthy safety study.
The efficacy study focused on 705 treatment-resistant patients recruited out of its Phase III program who were stable after 16 weeks of therapy with esketamine and an oral anti-depressant. Following another stretch of treatment, the esketamine combo proved significantly more effective in preventing a relapse than a placebo spray plus oral depression drug.
About one in four (26.7%) of the stable remitters in the esketamine arm experienced a relapse compared to 45.3% of the placebo group (p=0.003) — a strongly positive outcome. It’s particularly significant that the researchers were able to track longterm responses for a drug known for its ephemeral impact.
The safety data are a little more complex. As seen earlier, and completely expected, there was a high rate of dissociation — 22.4%. That underscores why J&J plans to have the drug infused in a clinic, with an observation period to make sure patients were behaving normally before they leave.
Esketamine is a low dose of ketamine, a party drug and horse tranquilizer that’s often abused. J&J here is trying to navigate its way through Phase III with an acceptable formulation for a tough patient population in a field known for widespread failure.
The safety study was open label, with patients aware they were getting the drug. Researchers reported:
Fifty-five (6.9%) patients experienced 68 serious treatment-emergent adverse events. Of these, five serious treatment-emergent adverse events from four subjects were assessed by the investigator as esketamine nasal spray-related. There were two deaths which the investigator determined to be unrelated to esketamine nasal spray or oral antidepressant use. Laboratory tests, physical examination, and nasal tolerability revealed no trends of clinical concern in patients treated with esketamine nasal spray for up to 52 weeks. No clinically meaningful changes in cognition were found. No cases of interstitial or ulcerative cystitis were reported.
I asked a company rep what the five serious adverse events were, as it could be relevant to a regulatory review. Her response: depression, delirium, anxiety and delusion, suicidal ideation and suicide attempt.
J&J has listed esketamine as one of its top late-stage development programs, prepping applications for both sides of the Atlantic. They’re not home free yet, but in depression uniform safety and efficacy is unheard of, with regulators willing to balance the risks with the benefits for a tough group to treat.
On that score, J&J is well ahead of the game.
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