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Reviva and FDA Reach Consensus on Brilaroxazine Clinical Trials for Schizophrenia NDA

Tuesday, April 16, 2024

Reviva Pharmaceuticals Holdings, Inc. (NASDAQ: RVPH), a prominent late-stage pharmaceutical company specializing in addressing unmet medical needs in central nervous system (CNS), inflammatory, and cardiometabolic diseases, made significant advancements in its brilaroxazine program for schizophrenia, gaining alignment with the U.S. Food and Drug Administration (FDA) on its Phase 3 development plan.

The FDA's acceptance of the 4-week RECOVER-2 study for brilaroxazine in schizophrenia marks a crucial step forward. Particularly noteworthy is the FDA's indication that two positive Phase 3 studies demonstrating efficacy at week 4, accompanied by at least 12 months of long-term safety data, could support a New Drug Application (NDA) submission for the acute treatment of schizophrenia. Moreover, the FDA stipulated the necessity of a long-term randomized withdrawal study post-approval to substantiate the maintenance of effect.

"We are delighted to receive positive feedback from the FDA and approval of our 4-week registrational study for the brilaroxazine program," said Dr. Laxminarayan Bhat, Founder, President, and CEO of Reviva. "The FDA's clarification regarding our NDA submission, which may include two 4-week Phase 3 studies demonstrating efficacy and a 12-month long-term safety study, is encouraging. Notably, we have already completed and disclosed the results of our pivotal Phase 3 RECOVER trial in October 2023. We are poised to commence our RECOVER-2 trial this quarter, with topline data from our 1-year OLE trial anticipated in the fourth quarter of this year. We anticipate fulfilling all outlined NDA submission requirements by the third quarter of 2025."

RECOVER-2 is a global Phase 3, randomized, double-blind, placebo-controlled, multicenter study designed to evaluate the safety and efficacy of brilaroxazine in approximately 450 patients with acute schizophrenia compared to placebo. Brilaroxazine will be administered at fixed doses of 30 mg or 50 mg once daily for 28 days. The primary endpoint is the reduction in Positive and Negative Symptoms Assessment total score compared to placebo from baseline to Day 28. Key secondary endpoints include clinical global impression (CGI) severity, positive and negative symptoms, social functioning, cognition, and key biomarkers implicated in neuroinflammation. Reviva intends to initiate the first clinical site for this trial in the current quarter (Q2-2024).

Schizophrenia is a debilitating neuropsychiatric disorder affecting approximately 1% of the global population, with around 3.5 million individuals in the United States and 20 million worldwide affected. Patients with schizophrenia experience a range of symptoms, including cognitive impairment, delusions, hallucinations, and disorganized speech or behavior. Current treatments often fall short in adequately addressing the complex mix of symptoms associated with schizophrenia, leading to suboptimal efficacy, poor tolerability, and low patient adherence rates.

Brilaroxazine, an internally discovered new chemical entity, exhibits potent affinity and selectivity against key serotonin and dopamine receptors implicated in schizophrenia and its comorbid symptoms. Positive topline data from the global Phase 3 RECOVER-1 trial demonstrated statistically significant and clinically meaningful reductions across all major symptom domains at week 4 with 50 mg of brilaroxazine compared to placebo, with a generally well-tolerated side effect profile and lower discontinuation rates than placebo. Additionally, promising nonclinical activity has been observed for brilaroxazine in inflammatory diseases such as psoriasis, pulmonary arterial hypertension (PAH), and idiopathic pulmonary fibrosis (IPF), with mitigation of fibrosis and inflammation in translational animal models. Brilaroxazine has received Orphan Drug Designation by the U.S. FDA for the treatment of PAH and IPF conditions.

Reviva intends to explore the development of brilaroxazine for other neuropsychiatric indications, including bipolar disorder, major depressive disorder (MDD), and attention-deficit/hyperactivity disorder (ADHD).



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