Princeton, NJ and Deerfield, IL — Otsuka Pharmaceutical, Co. Ltd. (Otsuka) and H. Lundbeck A/S (Lundbeck) announce the U.S. Food and Drug Administration (FDA) has determined that the supplemental New Drug Application (sNDA) for brexpiprazole in combination with sertraline for the treatment of adults with post-traumatic stress disorder (PTSD) is sufficiently complete to permit a substantive review. The FDA has assigned the application for a Prescription Drug User Fee Act (PDUFA) target action date of February 8, 2025.

The sNDA submission is based on data from three randomized clinical trials evaluating the safety and efficacy of brexpiprazole in combination with sertraline in adult patients with PTSD.

The primary endpoint for all three trials was the change from randomization (Week 1) to Week 10 in the Clinician-Administered PTSD Scale (CAPS-5) total score for brexpiprazole and sertraline combination therapy versus sertraline plus placebo in patients diagnosed with PTSD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).

The trials were randomized, double blind, active-controlled, and Trial 061 (Phase II) and 071 (Phase III) were flexible dose trials, while Trial 072 (Phase III) was a fixed dose trial.¹ In Trial 061 and 071, brexpiprazole in combination with sertraline was associated with a statistically significant reduction (p<0.05) in PTSD symptoms compared to sertraline plus placebo, as measured by the change in the CAPS-5 total score from randomization (Week 1) to Week 10 (primary endpoint). In Trial 072, while the primary endpoint was not met, reductions in PTSD symptoms with brexpiprazole in combination with sertraline were consistent with Trials 061 and 071. Improvements were consistently observed across the Clinical Global Impression Severity (CGI-S) scale and the four CAPS-5 clusters of re-experiencing, avoidance, negative cognition/mood and arousal/reactivity symptoms in Trials 061 and 071.

Across the three randomized trials, the combination of brexpiprazole and sertraline in adult patients with PTSD was generally well-tolerated, and no new safety observations were identified. The safety and tolerability results were consistent with the known profile of brexpiprazole in its approved indications and what has been observed in other clinical trials. The overall incidence of treatment-emergent adverse events (TEAEs) across the three trials was 55.5 percent with brexpiprazole plus sertraline, and 56.2 percent with sertraline plus placebo.²

“Post-traumatic stress disorder is one of the most common mental health disorders in the United States. Approximately 13 million adults in the U.S. have PTSD during a given year, and between seven to eight out of every 100 will experience PTSD at some point in their lives,” said John Kraus, M.D., Ph.D., executive vice president and chief medical officer, Otsuka. “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.”

“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, Ph.D., executive vice president, Lundbeck Research & Development. “We are grateful to the patients and caregivers who participated in these important trials.”