Spravato’s monotherapy nod on Tuesday comes after a series of setbacks in the depression space.
With an FDA nod on Tuesday, Johnson & Johnson’s esketamine nasal spray Spravato became the industry’s first monotherapy approved for use in adults with treatment-resistant depression.
The approval gives J&J a boost in a space that has been difficult to crack for biopharma, marked by a series of setbacks in the last year or so.
Earlier this month, for instance, Neumora Therapeutics’ closely watched navacaprant failed a late-stage study in major depressive disorder (MDD), unable to significantly lessen the severity of depressive episodes in treated patients. In December 2024, Relmada was forced to stop two Phase III trials of its MDD hopeful REL-1017 after a futility review came out against its favor.
Perhaps most notable was the failure of Biogen and Sage to secure an MDD approval for their pill Zurzuvae, which the FDA in August 2023 cleared for postpartum depression. However, in MDD—a much larger market—the regulator found that the partners did not provide “substantial evidence of effectiveness” for Zurzuvae.
With Tuesday’s regulatory win, Spravato can now be used without an oral antidepressant in adult patients who had shown inadequate response to at least two oral therapies. The approval was backed by data from a Phase IV study, which showed that Spravato monotherapy elicited a “rapid and superior improvement” in scores on the Montgomery-Asberg Depression Rating Scale versus placebo, according to the pharma’s announcement.
Additionally, 22.5% of Spravato-treated patients hit remission at four weeks, as opposed to 7.6% in placebo comparators.
As for safety, Spravato’s adverse event profile in the study was consistent with what has been reported in the literature, with no new signals of concern. The nasal spray comes with a boxed warning for sedation, dissociation and suicidal thoughts and behaviors. Spravato is also prone to abuse and misuse.
“For too long, healthcare providers have had few options to offer patients much-needed symptom improvement,” Bill Martin, Global Therapeutic Area Head of Neuroscience at J&J Innovative Medicines, said in a statement. Spravato’s approval as a monotherapy, he added, could help patients “experience improvements in depressive symptoms as early as 24 hours and at 28 days – without the need for daily oral antidepressants.”
Esketamine, the active ingredient in Spravato, is a non-selective, non-competitive antagonist of the NMDA receptor, a known target in depression. Since its initial approval in 2019, Spravato has become one of J&J’s high-growth brands, surging around 55% year-over-year in the third quarter of 2024 to bring in $284 million worldwide.
J&J is expected to report its fourth-quarter and full-year results on Wednesday.
Correction (Jan. 28): This story has been updated from its original version to state that the new approval for Spravato was in treatment-resistant depression, not major depressive disorder. BioSpace regrets the error.
