FDA Accepts Otsuka and Lundbeck’s Supplemental New Drug Application for Brexpiprazole with Sertraline for Adults with Post-Traumatic Stress Disorder

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The FDA has accepted Otsuka Pharmaceutical and Lundbeck Pharmaceuticals’ supplemental New Drug Application (sNDA) for brexpiprazole in combination with sertraline for the treatment of adults with post-traumatic stress disorder (PTSD). According to a joint statement, the sNDA is supported by encouraging data across three randomized clinical trials that evaluated the safety and efficacy of the combination therapy in adult patients with PTSD.¹

“[PTSD] is one of the most common mental health disorders in the United States. Approximately 13 million adults in the US 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, MD, PhD, EVP, chief medical officer, Otsuka, in a press release. “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.”

All three of the clinical trials were randomized, double blind, active-controlled studies, with Trial 061 (Phase II) and 071 (Phase III) being flexible-dose trials, while Trial 072 (Phase III) was a fixed-dose trial. The primary endpoint of the 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).

Results from Trials 061 and 071 demonstrated a statistically significant reduction in PTSD symptoms with the combination therapy compared to placebo. Despite Trial 072 not meeting the primary endpoint, it showed consistent symptom reductions. Additionally, improvements were observed consistently 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.

In all three trials, the combination of brexpiprazole and sertraline was generally well-tolerated, with no new safety signals reported. Further, safety and tolerability results lined up consistently with the known profile of brexpiprazole in its approved indications and data from previous clinical trials. Across the three trials, treatment-emergent adverse events (TEAEs) were reported in 55.5% of participants treated with brexpiprazole plus sertraline, and 56.2% in those treated with sertraline plus placebo.

In 2015, brexpiprazole was first approved in the United States as an adjunctive therapy to antidepressants in adults with major depressive disorder and as a treatment for adults with schizophrenia. Recent approvals include the treatment of agitation associated with dementia due to Alzheimer disease by the FDA in May 2023 and for agitation associated with dementia due to Alzheimer disease by Health Canada earlier this year.¹

According to the American Psychiatric Association, PTSD affects around 3.5% of adults in the United States annually. It is also estimated that one in 11 people will be diagnosed with PTSD during their lifetime, with women twice as likely to develop the condition than men.²

“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, EVP, Lundbeck Research & Development, in the press release. “We are grateful to the patients and caregivers who participated in these important trials.”

The FDA has set a Prescription Drug User Fee Act target action date of February 8, 2025.¹

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). Lundbeck. June 25, 2024. Accessed July 25, 2024. https://www.newsroom.lundbeckus.com/news-release/2024/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

2. What is Posttraumatic Stress Disorder (PTSD)? American Psychiatric Association. Accessed July 25, 2024. https://www.psychiatry.org/patients-families/ptsd/what-is-ptsd#:~:text=PTSD%20affects%20approximately%203.5%20percent,as%20men%20to%20have%20PTSD.