Larry Ereshefsky, PharmD: Brilaroxazine Improves Schizophrenia Symptoms

A phase 3 study found brilaroxazine at 50 mg and 15 mg significantly reduced symptoms of acute schizophrenia.¹

The pivotal RECOVER trial was led by Laxminarayan Bhag, from Reviva Pharmaceuticals, to assess the safety and efficacy of brilaroxazine: a serotonin-dopamine system modulator targeting D2/3/4 and 5-HT1A/2A receptors as a partial agonist and 5-HT2B/7 receptors as an antagonist.² Brilaroxazine controls inflammatory cytokines, a potential disease driver. The primary endpoint of improvement in the PANSS score from baseline to day 28, compared with placebo.

Participants on brilaroxazine 50 mg achieved a 10.1-point reduction compared to placebo (-23.9 vs -13.8; P < .001). Investigators observed significant reductions in positive, negative, and negative marder symptoms, as well as PANSS social cognition, excitement or agitation, PSP, and CGI-S. Brilaroxazine 15 mg was superior to placebo for all endpoints.

In an interview with HCPLive, Larry Ereshefsky, PharmD, the chief scientific officer at CenExcel Research and Follow the Molecule, discussed the RECOVER trial, from how brilaroxazine improves various symptom domains of schizophrenia to the drug’s safety profile.

When asked if brilaroxazine brought any notable adverse events, Ereshefsky responded, "The fascinating part is if they’re not notable.” He continued by saying how “remarkable” the safety profile was, with an all-cause discontinuation rate of 16%. During the phase 3 trial, the number of patients discontinuing the trial due to treatment-emergent adverse events was 0.

Some adverse events were sedation and restlessness, which was all depending on a participant’s sensitivity to the drug.

“That's why you need multiple doses for this drug,” Ereshefsky said. “I'm not a believer that one dose fits everybody.”

He also dived into the effects of brilaroxazine on inflammatory cytokines and neuroinflammation and how this can impact future treatment strategies. Every single psychotic episode damages the brain, shrinking the tissue. He said if future studies continue to show promise, this drug could potentially prevent the brain damage that occurs in schizophrenia, particularly in early treatment.

“Long term, changing the inflammatory system…could be a game changer,” Ereshefsky said. “It’s a little bit tangential, but it illustrates how different this drug seems to be from others.”

Investigators are considering examining the drug for the treatment of psoriasis, pulmonary disease, hypertension, fibrotic illness—all of which have nothing to do with schizophrenia.

“Yet this drug seems to have a signal here, so that that's a story still unfolding, but it is something that could differentiate,” Ereshefsky said.

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 25, 2024.}
2. ^{Bhat, L, Bhat, S, Ramakrishnan, A. Brilaroxazine Efficacy and Safety in the Phase 3 RECOVER Trial in Acute Schizophrenia. ASCPT Annual Conference in Colorado Springs, USA on March 27 – 29, 2024.}