J&J Submits sNDA for Esketamine Monotherapy in Treatment-Resistant Depression

Johnson & Johnson announced on July 22, 2024 the submission of a supplemental New Drug Application (sNDA) to the US Food and Drug Administration (FDA) for the approval of esketamine (SPRAVATO), a CIII nasal spray, as a monotherapy for adults with treatment-resistant depression.¹

The submission is backed by more than a decade of research, 31 clinical trials, and over 5 years of real-world use that showcase the safety and efficacy of SPRAVATO.

Back in 2019, the FDA approved SPRAVATO in combination with an oral antidepressant to treat adults with treatment-resistant depression. In 2020, the FDA approved SPREVATO for the treatment of depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior.²

Nearly 30 percent of the estimated 280 million people worldwide living with major depressive disorder have treatment-resistant depression, meaning they do not respond to ≥ 2 oral antidepressants.¹ If esketamine gets approved as a monotherapy, patients will no longer have to take an oral antidepressant as a part of their treatment regimen.

The FDA submission is supported by positive results from the phase 4 TRD4005 study that evaluated the efficacy, safety, and tolerability of esketamine as a monotherapy for depressive symptoms in adult patients with treatment-resistant depression. In the randomized, double-blind, multicenter, placebo-controlled trial participants took either esketamine monotherapy at either 56 mg or 84 mg, administered biweekly, or a placebo nasal spray.³ The study demonstrated a statistically significant and clinically meaningful rapid change in the Montgomery-Asberg Depression Rating Scale (MADRS) total score as early as 24 hours after the first esketamine dose with persistent improvements through 4 weeks of treatment.¹

The trial also showed the safety profile of esketamine was comparable to that of esketamine in combination with an oral antidepressant. Investigators did not identify any new safety concerns.

Esketamine may increase blood pressure, problems with thinking clearly, and bladder issues. Other common adverse events, which usually occur right after taking esketamine but go away the same day, include feeling disconnected from yourself, dizziness, nausea, sleepiness, spinning sensation, decreased feeling of sensitivity, anxiousness, lack of energy, vomiting, feeling drunk, and feeling extra happy or excited.

“Many patients living with challenging-to-treat depression spend far too long cycling through multiple treatments that don’t effectively resolve their symptoms, which can cause a significant functional and emotional burden on patients and their loved ones,” said Bill Martin, PhD, Global Therapeutic Area Head, Neuroscience, Johnson & Johnson Innovative Medicine, in a statement. “We’re pleased to build on the more than a decade of research reinforcing the safety and efficacy of SPRAVATO® and look forward to working with the FDA to bring this innovative treatment to patients as a monotherapy option.”

References

1. ^{Johnson & Johnson Seeks U.S. FDA Approval Of SPRAVATO® (Esketamine) As the First and Only Monotherapy For Adults With Treatment-Resistant Depression. Johnson & Johnson. July 22, 2024. https://www.jnj.com/media-center/press-releases/johnson-johnson-seeks-u-s-fda-approval-of-spravato-esketamine-as-the-first-and-only-monotherapy-for-adults-with-treatment-resistant-depression. Accessed July 22, 2024.}
2. ^{Kunzmann, K. FDA Approves Esketamine for Depressive, Suicidal Symptoms. HCPLive. August 4, 2020. https://www.hcplive.com/view/fda-approves-esketamine-depressive-suicidal-symptoms. Accessed July 22, 2024.}
3. ^{Johnson & Johnson Pivotal Study of Seltorexant Shows Statistically Significant And Clinically Meaningful Improvement In Depressive Symptoms And Sleep Disturbance Outcomes. Johnson & Johnson. May 29, 2024. https://www.jnj.com/media-center/press-releases/johnson-johnson-pivotal-study-of-seltorexant-shows-statistically-significant-and-clinically-meaningful-improvement-in-depressive-symptoms-and-sleep-disturbance-outcomes. Accessed July 22, 2024.}