Esketamine nasal spray misses key trial expectations, but Janssen remains optimistic

Janssen Pharmaceutical Companies of Johnson & Johnson encountered a significant setback with their esketamine nasal spray in a phase 3 trial aimed at treating patients with treatment-resistant depression. The trial’s results revealed that esketamine did not meet its primary endpoint, sparking concern among industry experts and stakeholders.

The late-stage study assessed the efficacy of two fixed doses of esketamine—56 mg and 84 mg—when combined with an oral antidepressant, compared to a placebo plus oral antidepressant. The trial’s primary endpoint was a change in depression severity rating scale scores from baseline to four weeks. Unfortunately, the 84 mg dose of esketamine failed to show statistical significance against the oral antidepressant plus placebo group.

Janssen disclosed that due to the 84 mg dose’s lack of statistical significance, the company was unable to formally evaluate the 56 mg dose group in the trial, according to the prespecified analysis plan. Nevertheless, numerical analyses suggested that esketamine, when combined with an oral antidepressant, might offer more benefits than the placebo combination.

Husseini K. Manji, Global Head of the Neuroscience Therapeutic Area at Janssen Research & Development, expressed cautious optimism about the findings. He remarked, “Together with the recently announced results from four other Phase 3 studies, these data provide continued support for a positive benefit-risk assessment for esketamine nasal spray as a potentially novel treatment approach for patients living with treatment-resistant depression.” Manji highlighted the urgent need for new treatments for the one-third of patients with major depressive disorder who do not respond to existing therapies.

Earlier this month, Janssen filed a New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) seeking approval for esketamine as a treatment for treatment-resistant depression in adults. This application is bolstered by data from five pivotal phase 3 trials, which showed that esketamine, alongside a newly initiated oral antidepressant, led to a quicker reduction in depressive symptoms and a delayed relapse compared to placebo.

Esketamine, a glutamate receptor modulator, aims to restore synaptic connections in brain cells affected by major depressive disorder, offering a novel mechanism compared to current treatments. The U.S. FDA had previously granted Breakthrough Therapy Designations to esketamine for treatment-resistant depression and for major depressive disorder with imminent risk for suicide.

In related news, Janssen recently received marketing authorization from the European Commission (EC) for daratumumab as an initial therapy for multiple myeloma in specific patient populations.