FDA accepts supplemental new drug application of Rexulti for PTSD

The FDA has accepted a supplemental new drug application from Otsuka and Lundbeck for Rexulti in combination with sertraline to treat adults with PTSD.

According to a joint company press release, acceptance was based on data from three randomized, double-blind, active-controlled clinical trials evaluating the safety and efficacy of the combination therapy.

"If approved, brexpiprazole and sertraline combination treatment would constitute a new therapeutic option for PTSD, a condition that has not seen any new pharmacological treatments approved by the FDA in more than 20 years,” Johan Luthman, DDS, PhD, executive vice president, Lundbeck Research and Development, told Healio in an email.

The primary endpoint for all three trials was change from randomization at week 1 to week 10 in the Clinician-Administered PTSD Scale (CAPS-5) total score for Rexulti (brexpiprazole, Otsuka/Lundbeck) and sertraline combination therapy compared with sertraline and placebo. The phase 2 trial 061 and phase 3 trial 071 were flexible dose, while the phase 3 trial 072 was fixed dose.

In trials 061 and 071, brexpiprazole plus sertraline was associated with a statistically significant reduction in PTSD symptoms compared to sertraline plus placebo, as measured by the change in the CAPS-5 total score, the release stated. In addition, improvements were consistently reported in these trials across the Clinical Global Impression Severity Scale and CAPS-5 clusters of re-experiencing, avoidance, negative cognition and mood, and arousal and reactivity symptoms.

In trial 072, reductions in PTSD symptoms with brexpiprazole in combination with sertraline were consistent with trials 061 and 071, although the primary outcome was not met.

Across the three trials, brexpiprazole plus sertraline appeared to be generally well-tolerated, with no new safety observations. Safety and tolerability were consistent with the known profile of brexpiprazole in its approved indications, the companies stated.

The FDA, which previously accepted a supplemental NDA for Rexulti to treat Alzheimer’s agitation and in October 2021 for its use to treat schizophrenia in adolescents in October 2021 assigned a Prescription Drug User Fee Act (PDUFA) target action date of Feb. 8, 2025.

“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,” John Kraus, MD, PhD, Otsuka’s executive vice president and chief medical officer, said in the 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.”

Editor's note: This story was updated on July 12, 2024 to include a quote from a Lundbeck spokesperson.