Five years after getting the US approval for Spravato (esketamine) nasal spray, Johnson & Johnson (J&J) has won a label expansion for the ketamine-derived drug allowing for the therapy’s use as a monotherapy in adults with major depressive disorder (MDD).
The US Food and Drug Administration (FDA) first approved Spravato in 2019 as a combination therapy with an oral antidepressant for treatment-resistant depression in adults. In 2020, the US regulatory agency expanded the therapy’s label to treat depressive symptoms in adults with MDD with acute suicidal ideation or behavior.
“Spravato is now available as a standalone treatment, meaning patients may experience improvements in depressive symptoms as early as 24 hours and at 28 days – without the need for daily oral antidepressants,” said Dr. Bill Martin, Global Therapeutic Area Head, Neuroscience, Johnson & Johnson Innovative Medicine.
Spravato is a high-grossing drug in J&J’s neuroscience portfolio. The therapy generated about $1.08 billion in global sales last year, up from $689 million it raked in 2023, according to J&J’s Q4 2024 financials.
Trial data
Spravato is a ketamine-derived drug. It is a non-selective, non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor. While the exact mechanism of action is unknown, it is believed to work differently by acting on a pathway in the brain that affects glutamate.
The FDA priority review approval of Spravato was based on positive data from a placebo-controlled study. The trial reported a rapid and superior improvement in Montgomery-Asberg Depression Rating Scale (MADRS) total score with Spravato, compared to placebo.
In a post-hoc analysis, the ketamine-derived drug demonstrated “numerical improvements” across all 10 MADRS items at 28 days.After four weeks, 22.5% of patients taking Spravato achieved remission (MADRS total score ≤ 12), compared to 7.6% of patients in the placebo group.
The most adverse effects of Spravato include mental effects such as feelings of disconnection, anxiousness, dizziness, and sleepiness, along with nausea, vomiting, and increased blood pressure.
Due to the potential for abuse and misuse along with the risks for sedation, dissociation, and respiratory depression, Spravato’s availability is regulated through a restricted program, Risk Evaluation and Mitigation Strategy (REMS) Program.
