Advancing Brilaroxazine Research in Schizophrenia with Larry Ereshefsky, PharmD

Brilaroxazine at 50 mg and 15 shows promise in significantly reducing symptoms of acute schizophrenia.

In an interview with HCPLive, investigator Larry Ereshefsky, PharmD, the chief scientific officer at CenExcel Research and Follow the Molecule discussed the efficacy, safety, and next steps for brilaroxazine research.^1,2

Reviva Pharmaceuticals assessed brilaroxazine, a serotonin-dopamine system modulator, in the phase 3 RECOVER trial led by Laxminarayan Bhag, PhD. Brilaroxazine targets D2/3/4 and 5-HT1A/2A receptors as a partial agonist and 5-HT2B/7 receptors as an antagonist. The drug controls inflammatory cytokines, which may serve as a disease driver.

Participants on brilaroxazine 50 mg achieved a 10.1-point reduction compared to placebo in the PANSS score (-23.9 vs -13.8; P < .001), as well as had improvements in positive, negative, and negative marder symptoms; PANSS social cognition, excitement or agitation, PSP, and CGI-S. Participants on brilaroxazine 15 mg had improvements on all endpoints compared to placebo.

Ereshefsky suggests brilaroxazine may not just be effective for treating symptoms of schizophrenia—he said the drug is “likely to be useful” in other psychiatric conditions, such as bipolar disorder and ADHD.

“Mechanistically, something is quite different here,” he said.

More than that, brilaroxazine may treat conditions in areas other than the psychiatric field. Since brilaroxazine controls areas of neuroinflammation and damage caused by inflammatory processes, the drug can potentially treat individuals with brain disease. Ereshefsky said because of brilaroxazine’s mechanism, investigators would like to assess brilaroxazine for pulmonary diseases, fibrosis, arterial hypertension, and psoriasis.

Ereshefsky explained the team needs to explore the link between brilaroxazine and weight gain. The phase 3 trial showed there were a weak association between brilaroxazine and weight gain, unlike the phase 2 trial, thus assessing this in a long-term study is important.

Ereshefsky said he is looking forward to working on the second phase 3 trial, and although he hopes the results will replicate RECOVER, clinical trials are always a challenge.

“You can't bet 100% on anything in psychiatry working, but this, I think, is a solid drug,” Ereshefsky said. “And it's going to be an important addition to the armamentarium, so I'm hoping to see this drug get to patients in the real world soon.”

There were no reported disclosures for Ereshefsky.

References

1. ^{Derman, C. Phase 3 Data on Brilaroxazine for Schizophrenia with Larry Ereshefsky, PharmD. HCPLive. April 24, 2024. https://www.hcplive.com/view/phase-3-data-on-brilaroxazine-for-schizophrenia-with-larry-ereshefsky-pharmd. Accessed April 26, 2024.}
2. ^{Derman, C. Larry Ereshefsky, PharmD: Brilaroxazine Improves Schizophrenia Symptoms. HCPLive. April 26, 2024. https://www.hcplive.com/view/larry-ereshefsky-pharmd-brilaroxazine-improves-schizophrenia-symptoms. Accessed April 26, 2024.}