Open Label Phase 3 Study of Brilaroxazine for Schizophrenia Shows Efficacy, Tolerability

Reviva Pharmaceuticals announced positive results from their phase 3 RECOVER open label extension of brilaroxazine (RP5063) for patients with schizophrenia.^1,2 The trial looked at long-term safety, tolerability, and efficacy of once daily brilaroxazine over a 1-year period.

According to Reviva, the data for brilaroxazine, a novel serotonin dopamine signaling modulator with demonstrated selectivity for other receptors, showed “robust broad-spectrum efficacy that was sustained over 1-year and was generally well tolerated with a discontinuation rate of 35% in this long-term study.” ¹

The RECOVER trial included 446 patients with schizophrenia who received either 15 mg (N=140), 30 mg (N=158), or 50 mg (n=148) brilaroxazine. Investigators found improvements as measured by Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity (CGI-S) scores at 6 months, 12 months, and for rollover patients into the open label extension at 13 months. ¹

In addition, the RECOVER trial found brilaroxazine had a well-tolerated safety profile across the 3 doses, with only 8.5% of participants reporting at least 1 treatment adverse event. The majority of such events were transient and considered mild (6.5%) or mild (2.5%) in nature. Headache (2.7%), insomnia (4.0%), sleep disturbance (2.9%), and mild tremor (3.1%) were among the most common treatment-emergent adverse events. Interestingly, although mild weight gain (1.52 kg) was reported over 1 year treatment, weight gain was not dose-dependent, with the least gain associated with the 50 mg dose. There was no evidence of clinically meaningful changes in movement disorder scales nor were there any serious adverse events observed. (Five serious adverse events were reported but none were deemed related to the trial medication.) ¹

Laxminarayan Bhat, PhD, founder, president and chief executive officer of Reviva Pharmaceuticals Holdings Inc, discussed the results in an interview with Psychiatric Times.

“Schizophrenia is primarily caused by dysfunctional dopamine serotonin signaling pathways,” Bhat told Psychiatric Times. “All the standard of care agents currently available, by and large, address dopamine D2 and the 5SD2A target. Our drug also target these 2 receptors with the differential activity partial agonist for both receptors.”

In addition, brilaroxazine “has potent activity almost 3 to 4 times more potent for a receptor called 5-HT2B that is highly expressed in the neural network,” he added. “There is a lot of clinical literature available to implicate that 5-HT2B is an upstream target to mediate neuroinflammation in the brain.” Bhat explained it is also implicated in the chronicity of schizophrenia, including the negative symptoms, depressive symptoms, and cognition.”

Bhat also discussed the drug’s tolerability, noting “minimal or no activity for certain targets that's known to cause cardiac side effect, GI side effect, and then motor side effect, all these things very well translated in the data.”

Altogether, “these are the key differentiating factors with respect to basic pharmacology of the drug,” he said.

Reviva is exploring ways to expedite new drug application process with the US Food and Drug Administration based on the results of this and previous studies. Simultaneously, they are planning another potential phase 3 study to ensure the process moves forward.

Bhat told Psychiatric Times brilaroxazine holds great promise. “We believe if it is approved and goes to a market, it would benefit significant, millions of people.”

References

1. Reviva Announces Positive Full Dataset for 1-Year Phase 3 RECOVER Open Label Extension Study Evaluating Brilaroxazine in Schizophrenia. Press release. June 2, 2025. Accessed June 2, 2025. https://www.globenewswire.com/news-release/2025/06/02/3091710/0/en/Reviva-Announces-Positive-Full-Dataset-for-1-Year-Phase-3-RECOVER-Open-Label-Extension-Study-Evaluating-Brilaroxazine-in-Schizophrenia.html

2. Safety and Efficacy of Brilaroxazine (RP5063) in Schizophrenia (RECOVER). Updated December 19, 2024. Accessed June 2, 2025. https://clinicaltrials.gov/study/NCT05184335