Reviva Pharmaceuticals Holdings, Inc. announced that enrollment is complete in the pivotal Phase 3 RECOVER study evaluating brilaroxazine for schizophrenia, with 402 patients enrolled at multiple sites in the United States (~60%), Europe (~10%), and Asia (~30%). RECOVER is a global Phase 3, randomized, double-blind, placebo-controlled, multicenter study designed to assess the safety and efficacy of brilaroxazine in 402 patients with acute schizophrenia compared to placebo. Brilaroxazine will be administered at fixed doses of 15 mg or 50 mg once daily for 28 days.

The primary endpoint is a decrease in Positive and Negative Symptoms Assessment total score compared to placebo from baseline to Day 28. Key secondary endpoints include clinical global impression rating scale, positive and negative symptoms, social functioning and cognition. A 1-year open-label extension study with flexible doses of 15 mg, 30 mg, or 50 mg will further evaluate the long-term safety and tolerability of brilaroxazine in patients with stable schizophrenia.

Over 50% of patients are currently enrolled in the OLE, with completion of the required 100 patients treated with brilaroxazine for 1-year expected in Third Quarter 2024. Brilaroxazine is an in-house discovered new chemical entity with potent affinity and selectivity against key serotonin and dopamine receptors implicated in schizophrenia and its comorbid symptoms. In a multinational, multicenter, double-blind Phase 2 study in 234 patients with acute schizophrenia or schizoaffective disorder, brilaroxazine met its primary endpoint, reducing Positive and Negative Syndrome Scale (PANSS) total score and demonstrating statistically significant improvement of overall drug treatment outcomes using Clinical Global Impression scale and for secondary endpoints evaluating social functioning, and positive and negative symptoms, and directional improvements for depression and cognition. In this completed Phase 2 study, brilaroxazine met all safety endpoints with no weight gain, no increase in blood sugar and lipids, and no cardiac or endocrine adverse effects compared to placebo.

Positive data from a clinical drug-drug interaction study investigating the potential effect of CYP3A4 enzyme on brilaroxazine in healthy subjects supports no clinically significant interaction when combined with a CYP3A4 inhibitor. A full battery of regulatory compliant toxicology and safety pharmacology studies has been completed for brilaroxazine. The U.S. Food and Drug Administration has agreed to consider a potential superior safety label claim if there is a positive outcome on a relevant endpoint in a pivotal Phase 3 study in patients with schizophrenia.

Reviva intends to develop brilaroxazine for other neuropsychiatric indications including bipolar disorder, major depressive disorder and attention-deficit/hyperactivity disorder. Additionally, brilaroxazine has shown promising efficacy for inflammatory diseases psoriasis, pulmonary arterial hypertension (PAH) and idiopathic pulmonary fibrosis with mitigation of fibrosis and inflammation in translational animal models. Brilaroxazine has already received Orphan Drug Designation by the U.S. FDA for the treatment of PAH and IPF conditions.