Sure, they can treat the hallucinations and the delusions, but as for many other symptoms that can severely impact a patient's quality of life – such as a lack of motivation, a decreased ability to experience pleasure, a reduction in the ability to speak and express emotion and a lower social drive – the medicines haven't proven that effective. The inability to address those negative symptoms and some of the potential side effects with the current treatments, which include motor side effects, sexual dysfunction, weight gain, dyslipidemia and diabetes, tends to lead to patient nonadherence, another obstacle to treating the millions of people with schizophrenia.  

As it stands, 1.1% of the world's population suffers from schizophrenia. That's about 24 million people globally and 3.7 million in the U.S. alone. Of those sufferers, 30% are treatment-refractory, which means they are not responding to the treatments available today. Schizophrenia patients are also reported to suffer from neuroinflammation, and a persistent inflammatory state is seen as a major factor in treatment-resistant schizophrenia. Thus, an antipsychotic with anti-inflammatory activity can be an effective drug to treat schizophrenia, including those treatment-refractory patients.

It is for all of those reasons that Reviva Pharmaceuticals Inc. (NASDAQ:RVPH), a late clinical stage pharmaceutical company that discovers, develops and seeks to commercialize next generation therapeutics for diseases representing unmet medical needs and burdens to society, patients and their families, is aiming to transform the schizophrenia treatment market with a drug that targets both the dysfunctioned serotonin-dopamine signaling neurotransmitter pathways and neuroinflammation. 

After all, neuroinflammation is increasingly being implicated as a major contributing factor to schizophrenia, and that is where Reviva's brilaroxazine comes in. Brilaroxazine is a once-daily, serotonin-dopamine signaling modulator with the potential to reduce neuroinflammation. It works by modulating the activity of serotonin and dopamine receptors in the brain, acting as a partial agonist and antagonist, with the goal of stabilizing the serotonin/dopamine system involved in schizophrenia and other neuropsychiatric disorders, including neuroinflammation.

The company reports that the trials also demonstrated strong and sustained efficacy from acute to maintenance treatment over one year, with a large number of patients showing reductions in their Positive and Negative Syndrome Scale (PANSS) scores. The PANSS is a 30-item scale used to assess the major symptoms associated with schizophrenia, such as positive symptoms, negative symptoms, general psychopathology and social cognition. Consistent findings across trials support a well-tolerated safety profile, low discontinuation rate and durable, broad-spectrum efficacy across all major symptom domains, reports Reviva, noting there were no drug-related serious adverse events or major safety concerns reported, nor were there any motor, endocrine/sexual, cardiac/liver/GI side effects and low metabolic side effects. Plus, the discontinuation rate was low compared to the historical data reported for standard-of-care antipsychotics.

The long-term OLE portion of the company's RECOVER phase 3 trial was an important milestone for Reviva, as it is a requirement for it to submit an NDA to the U.S. FDA. An NDA is the formal process in which a drug company requests permission from the FDA to market a new drug in the U.S. The application includes demonstrating the drug's safety and effectiveness. The FDA requires long-term safety data from 100 patients who have completed 12 months of treatment. In the OLE trial, 159 patients completed 12 months of treatment and 301 completed 6 months of treatment. Reviva expects a pre-NDA meeting with the U.S. FDA to discuss brilaroxazine's path to approval for schizophrenia in Q4 2025 and potential NDA submission in Q2 2026. The outcome of these regulatory milestones could be catalysts for the company and its stock. 

Reviva may be on to something with brilaroxazine when it comes to treating schizophrenia. After all, brilaroxazine, once daily orally administered monotherapy, has proven to be safe and effective in clinical trials and does not have the motor side effects, and metabolic, endocrine, cardiac and gastrointestinal side effects reported for current standard of care antipsychotics in the market. It also demonstrated a superior treatment adherence profile compared to the historical data in similar clinical trials for the approved antipsychotics. Overall, brilaroxazine continues to demonstrate a differentiated and durable clinical profile, positioning it as a potential new standard of care in schizophrenia. 

But it is not only schizophrenia that Reviva believes it can treat with brilaroxazine. The company plans to expand into negative symptoms associated with schizophrenia, bipolar disorder, major depressive disorder, attention deficit hyperactivity disorder and other diseases of the brain. Brilaroxazine is projected as a pipeline-in-a-product for psychiatric diseases with an aggregate market size projected to reach over $50 billion by 2030. With an FDA meeting on the horizon and positive trial results in the rearview mirror, Reviva is a company to watch.