FDA Accepts sNDA for Brexpiprazole in Combination with Sertraline for Adult PTSD

Credit: US Food and Drug Administration

Otsuka and Lundbeck announced on June 25, 2024, the US Food and Drug Administration (FDA) accepted the supplemental New Drug Application (sNDA) filing for brexpiprazole in combination with sertraline for the treatment of adults with PTSD. The Prescription Drug User Fee Act (PDUFA) target action date for the completion of the review is February 8, 2025.¹

“Brexpiprazole in combination with sertraline could represent an important advancement over current standard of care, and we look forward to working with the FDA in the process of seeking approval of this combination,” said Johan Luthman, PhD, executive vice president of Lundbeck Research & Development.

Brexpiprazole is approved for other indications in the US, such as adjunctive therapy to antidepressants in adults with major depressive disorder (MDD) and schizophrenia in 2015 and the treatment of agitation associated with dementia due to Alzheimer’s disease in 2023.²

The sNDA submission package included 3 randomized, double-blind, active-controlled clinical trials evaluating the safety and efficacy of brexpiprazole in combination with sertraline in adult patients with PTSD.¹ All 3 trials had the primary endpoint of change in Clinician-Administered PTSD Scale total score from randomization (week 1) to week 10. Investigators compared the scores of the brexpiprazole group with the placebo group.

In the flexible-dose trials (1 phase 2, 1 phase 3), brexpiprazole in combination with sertraline was linked to a statistically significant reduction in PTSD symptoms (P < .05) compared to sertraline plus placebo, as measured by the change in the CAPS-5 total score from week 1 to week 10. The flexible-dose trials also showed consistent improvements across the Clinical Global Impression Severity (CGI-S) scale and the 4 CAPS-5 clusters of re-experiencing, avoidance, negative cognition/mood, and arousal/reactivity symptoms.

The fixed-dose phase 3 trial did not meet the primary endpoint but demonstrated similar reductions in PTSD symptoms with brexpiprazole in combination with sertraline to the flexible-dose trials.

Brexpiprazole in combination with sertraline was well-tolerated in all 3 trials with no new safety concerns. Across the 3 trials, the overall incidence of treatment-emergent adverse events (TEAEs) was 55.5% with brexpiprazole plus sertraline and 56.2% with sertraline plus placebo.

“This is a significant development, and we look forward to continuing our efforts to provide a treatment option that may benefit the millions of patients and caregivers who are impacted by the debilitating effects of PTSD,” said John Kraus, MD, PhD, executive vice president and chief medical officer of Otsuka.

References

1. ^{Otsuka and Lundbeck Announce FDA Acceptance of sNDA Filing for Brexpiprazole in Combination with Sertraline for the Treatment of Adults with Post-Traumatic Stress Disorder (PTSD). Business Wire. June 25, 2024. https://www.businesswire.com/news/home/20240625407910/en/Otsuka-and-Lundbeck-Announce-FDA-Acceptance-of-sNDA-Filing-for-Brexpiprazole-in-Combination-With-Sertraline-for-the-Treatment-of-Adults-With-Post-Traumatic-Stress-Disorder-PTSD. Accessed June 25, 2024.}
2. ^{Fitzpatrick, C. FDA Approves Drug for Schizophrenia and Major Depressive Disorder. HCPLive. June 13, 2015. https://www.hcplive.com/view/fda-approves-drug-for-schizophrenia-and-major-depressive-disorder. Accessed June 25, 2024.}