Brexpiprazole with Sertraline Significantly Reduces PTSD Symptoms in 10 Days

A phase 3 trial demonstrated that taking brexpiprazole alongside sertraline significantly reduced overall PTSD symptoms in 10 days compared with sertraline plus placebo.1 Otsuka Pharmaceutical and Lundbeck announced on December 18, 2024, that the full results of their phase 3 trial were published in JAMA Psychiatry.

“About 6% of the United States population will have PTSD at some point in their lives, but around only half will seek treatment,” said lead investigator Lori Davis, MD, clinical professor of psychiatry at the University of Alabama School of Medicine.2 “The Phase 3 results are an important and encouraging step forward in the hopes of providing PTSD patients with a new therapeutic option in the future.”

The publication of this data follows Otsuka and Lundbeck’s announcement on June 25, 2024, that 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.3 The FDA assigned the sNDA a Prescription Drug User Fee Act (PDUFA) target action date of February 8, 2025.

The recently published data was a phase 3 randomized, double-blind, active-controlled, parallel-arm trial conducted from October 2019 to August 2024.1 Investigators evaluated the efficacy, safety, and tolerability of brexpiprazole plus sertraline in 416 adult patients aged 18 – 65 years (mean age: 37.4 years; 74.5% female) with PTSD.1 The sample was mostly White (70%), followed by 21.2% Black or African American, 14.7% Hispanic or Latino, 3.1% Asian, 2.2% American Indian or Alaska Native, and 0.2% Native Hawaiian or other Pacific Islander.

Participants were randomized to receive either brexpiprazole (2 – 3 mg/day) with sertraline (150 mg/day) or sertraline (150 mg/day) with a placebo. The primary endpoint was the change in the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total score from randomization (week 1) to week 10.

The trial began with a 1-week placebo period followed by an 11-week double-blind, randomized, active-controlled, parallel-arm period and then a 21-day follow-up. The study had taken place at 86 clinical trial sites in the US.

Participants on brexpiprazole with sertraline experienced a statistically significant greater improvement in the CAPS-5 total score (-19.2) compared with those receiving sertraline with placebo (-13.6) (least squares mean difference, -5.59; 95% confidence interval [CI], -8.79 to -2.28; P < .001) by week 10. The study also met both secondary endpoints: change in the Clinical Global Impression-Severity of Illness score (CGI-S) from week 1 to 10 and Brief Inventory of Psychological Function (B-IPF) from week 0 to 12.

Brexpiprazole with sertraline showed a comparable safety profile to brexpiprazole in approved indications. Already approved indications include adjunctive therapy to antidepressants in adults with major depressive disorder and schizophrenia and the treatment of agitation linked to dementia due to Alzheimer Disease.2

A greater percentage of participants on placebo + sertraline discontinued due to adverse events (10.2%) compared to participants on brexpiprazole + sertraline (3.9%). However, more participants on brexpiprazole + sertraline experienced adverse events than those on placebo + sertraline, and common adverse events (incidence of ≥ 5%) included nausea (12.2% vs 11.7%), fatigue (6.8% vs 4.1%), weight gain (5.9% vs 1.5%), and somnolence (5.4% vs 2.6%, respectively.

“The outcome of this trial provides us with an opportunity to help patients with PTSD,” said Johan Luthman, executive vice president and head of Research & Development at Lundbeck, in a statement. “With these promising results, we are committed to working closely with the FDA to help bring brexpiprazole in combination with sertraline to the healthcare professionals serving the PTSD patient community.”

References

1. Davis LL, Behl S, Lee D, et al. Brexpiprazole and Sertraline Combination Treatment in Posttraumatic Stress Disorder: A Phase 3 Randomized Clinical Trial. JAMA Psychiatry. Published online December 18, 2024. doi:10.1001/jamapsychiatry.2024.3996
2. JAMA Psychiatry Publishes Results of Otsuka and Lundbeck's Phase 3 Trial of Brexpiprazole in Combination with Sertraline in Treatment of Post-Traumatic Stress Disorder (PTSD) in Adults. Otsuka. December 18, 2024. https://www.otsuka-us.com/news/jama-psychiatry-publishes-results-otsuka-and-lundbecks-phase-3-trial-brexpiprazole-combination. Accessed December 19, 2024.
3. Derman, C. FDA Accepts sNDA for Brexpiprazole in Combination with Sertraline for Adult PTSD. HCPLive. June 25, 2024. https://www.hcplive.com/view/fda-accepts-snda-for-brexpiprazole-in-combination-with-sertraline-for-adult-ptsd. Accessed December 19, 2024.