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sNDA for Brexpiprazole/Sertraline Combination for PTSD Submitted for FDA Review


The sNDA for the brexpiprazole plus sertraline therapy is based on positive phase 2 and 3 clinical trials showing improvement in PTSD-specific scale scores.

Based on data from several phase 3 and phase 2 clinical trials, Otsuka Pharmaceutical Co., Ltd. and H. Lundbeck A/S submitted a supplemental new drug application (sNDA) to the FDA for brexpiprazole in combination with sertraline in the treatment of posttraumatic stress disorder (PTSD) in adults.1

sNDA for Brexpiprazole/Sertraline Combination for PTSD Submitted for FDA Review / image credit  FDA logo: ©Araki Illustrations/stock.adobe.com
©Araki Illustrations/stock.adobe.com

The combination proved to be effective in a phase 3 randomized, double-blind, 2-arm, flexible dose trial (NCT04124614), meeting its primary endpoint by demonstrating improvements from baseline Clinician-Administered PTSD Scale (CAPS-5) scores at week 10 (P < .05).2,3 The study included 416 adults (aged 18–65 years) with DSM-5 diagnosis of PTSD for a minimum of 6 months who were randomly assigned to receive brexpiprazole (2-3 mg/day) plus sertraline or sertraline plus placebo. Up to 150 mg of sertraline were administered simultaneously with the placebo or brexpiprazole.

The second phase 3 study (NCT04174170) was a randomized, double-blind, 3-arm, fixed dose trial that sought to evaluate the combination's efficacy, safety and tolerability.2,4 The trial included a group who received fixed-dose brexpiprazole 2 mg/day plus sertraline 150 mg/day, a group who received brexpiprazole 3 mg/day plus sertraline 150 mg/day, and those who received sertraline 150 mg/day plus placebo. A total of 553 participants with a DSM-5 diagnosis of PTSD were included in the trial. This phase 3 trial, however, failed to meet the primary endpoint of reduction in CAPS-5 scores (P > .05).2,4

The results from both phase 3 studies were announced in September 2023. “The two trials constitute one of the largest clinical development programs ever conducted in PTSD. We will analyze the dataset to further determine the potential of brexpiprazole as combination therapy with sertraline in comprehensively addressing symptoms across the PTSD core domains,” Johan Luthman, DDS, PhD, executive vice president and head of Research & Development at Lundbeck, said in a press statement at the time.2

The clinical phase 2 study was also a flexible dose trial and included 321 patients with PTSD. It demonstrated statistical superiority of combination brexpiprazole and sertraline over sertraline plus placebo.

The studies also indicated that the drug combination was generally well-tolerated, with reports that the safety profile was similar to that seen with brexpiprazole in studies of other psychiatric conditions (ie, agitation associated with Alzheimer, schizophrenia, and adjunctive treatment of major depressive disorder).1,2 Dyspepsia, fatigue, weight increase, akathisia, and somnolence were the most commonly reported adverse events associated with the combination treatment. Interestingly, discontinuation rates due to adverse events was higher in the sertraline and placebo treatment groups than in the combination groups and were and 7.6% and 3.7%, respectively.

Brexpiprazole is currently approved by the FDA for the treatment of schizophrenia in adults, adjunctive therapy to antidepressants for major depressive disorder in adults, and in May 2023 received approval for the treatment of agitation associated with dementia due to Alzheimer disease.

This article originally appeared in Psychiatric Times.

1. Otsuka and Lundbeck submit sNDA for FDA review of brexpiprazole and sertraline combination as potential treatment for PTSD. News release. April 10, 2024. Accessed April 11, 2024. https://otsuka-us.com/news/otsuka-and-lundbeck-submit-snda-fda-review-brexpiprazole-and-sertraline-combination-potential
2. Otsuka Pharmaceutical and Lundbeck Announce Topline Results from Two Phase 3 Trials of Brexpiprazole as Combination Therapy with Sertraline for the Treatment of Post-Traumatic Stress Disorder in Adults. News release. September 7, 2023. Accessed April 11, 2024. https://otsuka-us.com/news/otsuka-pharmaceutical-and-lundbeck-announce-topline-results-two-phase-3-trials-brexpiprazole
3. Brexpiprazole as Combination Therapy With Sertraline in Treatment of Adults With PTSD. ClinicalTrials.gov Identifier: NCT04124614. Last updated September 1, 2023. Accessed April 4, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT04124614 4. Brexpiprazole as Combination Therapy With Sertraline in the Treatment of Adults With Post-traumatic Stress Disorder. ClinicalTrials.gov identifier: NCT04174170. Updated September 9, 2023. Accessed April 11, 2024. https://clinicaltrials.gov/study/NCT04174170

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