Reviva Confirms FDA Agreement on Brilaroxazine Trials for Schizophrenia NDA

April 15, 2024—Reviva Pharmaceuticals Holdings, Inc. (NASDAQ: RVPH), a pharmaceutical company in advanced stages of developing treatments for central nervous system (CNS) disorders, inflammatory diseases, and cardiometabolic conditions, announced a significant development. The company has received confirmation from the U.S. Food and Drug Administration (FDA) to proceed with its Phase 3 registrational program for brilaroxazine aimed at treating schizophrenia.

The FDA endorsed a 4-week RECOVER-2 study of brilaroxazine for acute schizophrenia. Significantly, the FDA mentioned that two positive Phase 3 studies showcasing efficacy at the four-week mark, combined with long-term safety data extending at least 12 months, might support a New Drug Application (NDA) for this condition. Additionally, the FDA will mandate a long-term randomized withdrawal study following approval to confirm sustained efficacy.

"We are thrilled with the FDA's positive feedback and the acceptance of our 4-week registrational study for brilaroxazine," stated Laxminarayan Bhat, Ph.D., Founder, President, and CEO of Reviva. "The FDA clarified that our NDA submission could include two 4-week Phase 3 studies that show efficacy, alongside a 12-month long-term safety study. We've already wrapped up our pivotal Phase 3 RECOVER trial successfully in October 2023, and we plan to start the RECOVER-2 trial this quarter. We aim to present topline data from our 1-year OLE trial by the end of this year. Collectively, we expect to meet all NDA requirements by the third quarter of 2025."

The RECOVER-2 study is a global Phase 3 trial, randomized, double-blind, placebo-controlled, and multicenter, over a 4-week period. It will evaluate the safety and efficacy of brilaroxazine in approximately 450 patients with acute schizophrenia, compared to a placebo. Participants will receive 30 mg or 50 mg of brilaroxazine daily for 28 days. The primary endpoint is a decrease in Positive and Negative Symptoms Assessment total score from baseline to Day 28. Secondary endpoints include clinical global impression (CGI) severity, positive and negative symptoms, social functioning, cognition, and biomarkers associated with neuroinflammation. Reviva plans to initiate the first clinical site this quarter (Q2 2024).

About Schizophrenia
Schizophrenia is a severe neuropsychiatric disorder affecting about 1% of the global population, including 3.5 million people in the United States and 20 million worldwide. Characterized by symptoms like cognitive impairment, delusions, hallucinations, and disorganized behavior, schizophrenia lacks treatments that comprehensively address this complex mix. Current therapies often fall short in efficacy, are poorly tolerated, and result in low patient adherence.

About Brilaroxazine
Brilaroxazine, a new chemical entity discovered in-house, targets key serotonin and dopamine receptors associated with schizophrenia. The Phase 3 RECOVER-1 trial demonstrated significant reductions in symptoms at week 4 with a 50 mg dose. These results showed brilaroxazine was well-tolerated, with side effects and discontinuation rates lower than placebo. A drug-drug interaction study also indicated no significant interaction with CYP3A4 inhibitors. In addition to schizophrenia, Reviva is exploring the potential of brilaroxazine for bipolar disorder, major depressive disorder (MDD), and attention-deficit/hyperactivity disorder (ADHD).

Furthermore, brilaroxazine has shown promising results against inflammatory diseases like psoriasis, pulmonary arterial hypertension (PAH), and idiopathic pulmonary fibrosis (IPF) in animal models. The FDA has granted Orphan Drug Designation for PAH and IPF treatment.

About Reviva
Reviva is focused on discovering, developing, and commercializing next-generation treatments for diseases with unmet medical needs. The company primarily targets CNS, inflammatory, and cardiometabolic diseases. Their current pipeline includes brilaroxazine (RP5063) and RP1208, both discovered in-house. Reviva holds composition of matter patents for these compounds in the United States, Europe, and other countries.