Phase 3 Data on Brilaroxazine for Schizophrenia with Larry Ereshefsky, PharmD

New phase 3 data found brilaroxazine at 50 mg and 15 mg significantly reduced symptoms of acute schizophrenia.^1,2

Investigators already conducted a phase 1 study with healthy volunteers and stable schizophrenia patients. A phase 2 study assessed the efficacy and safety of brilaroxazine in acute schizophrenia or schizoaffective disorder.

More recently, the team, led by Laxminarayan Bhat, from Reviva Pharmaceuticals, conducted the pivotal phase 3 RECOVER trial to assess safety and efficacy. RECOVER was a randomized, double-blind, placebo-controlled, multicenter study evaluating brilaroxazine in acute schizophrenia patients for 28 days. The primary endpoint being the PANSS score vs placebo from baseline to day 28, and the secondary endpoints were the positive and negative symptoms, PANSS social cognition, excitement/agitation, personal and social performance, clinical global impression severity, safety, and emergent adverse events.

Participants were considered to have acute schizophrenia if they had a Mean Baseline Positive and Negative Assessment (PANSS) score of 98.22). They were randomized to either receive 15 mg (n = 140), 50 mg (n = 134), or placebo (n = 137).

Investigators saw brilaroxazine 50 mg achieved a 10.1-point reduction compared to placebo (-23.9 vs -13.8; P < .001). They also saw significant reductions in positive (P < .001), negative (P = .003), negative marder symptoms (P = .002), PANSS social cognition (P < .001), excitement/agitation (P < .001), PSP (P < .001), and CGI-S (P < .001). Furthermore, brilaroxazine 15 mg was superior to placebo for all endpoints and significant for social cognition (P = .024) and PSP (P = .022).

Brilaroxazine is serotonin-dopamine signaling targeting D2/3/4 and 5-HT1A/2A receptors as a partial agonist and 5-HT2B/7 receptors as an antagonist. The drug helps control inflammatory cytokines which can be a disease driver.

“I'm an advocate for ways to treat the brain other than receptor blockade, and the area of neuroinflammation and damage done by inflammatory stress processes is really gaining support for Parkinson's, depression, Alzheimer's, and serotonin seems to modulate the anti-inflammatory processes in the brain,” said Larry Ereshefsky, PharmD, chief scientific officer at CenExcel Research and Follow the Molecule, in an interview with HCPLive. “So, this is another gear, possibly, for this drug [that] now needs confirmation.”

Ereshefsky told HCPLive the next step for the research is testing out the 30 mg dose of brilaroxazine for acute schizophrenia since the US Food and Drug Administration likes to know the minimum effective dose.

“It's likely 15 [mg] works in stable patients quite well, less ill patients, it could well be a maintenance dose that's being shown to be effective right now,” Ereshefsky said. “But for acute psychosis, where you're trying to control someone who's a danger to themselves or others, you need a drug with a higher dose that's been shown elsewhere.”

There are no reported disclosures for Ereshefsky.

References

1. ^{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.}
2. ^{Reviva to Present RECOVER Phase 3 Clinical Trial Data for Brilaroxazine in Schizophrenia at the SIRS 2024 Annual Meeting. March 28, 2024. https://revivapharma.com/reviva-to-present-recover-phase-3-clinical-trial-data-for-brilaroxazine-in-schizophrenia-at-the-sirs-2024-annual-meeting/. Accessed April 23, 2024.}