8-K: Reviva Pharmaceuticals Announces Positive Full Dataset from 1-Year Phase 3 Study of Brilaroxazine in Schizophrenia

Reviva Pharmaceuticals Holdings, Inc. reported a positive full dataset and successful completion of its Phase 3 RECOVER open-label extension study, demonstrating sustained efficacy and a well-tolerated safety profile for brilaroxazine in schizophrenia patients over one year.

Summary

• Reviva Pharmaceuticals announced the successful completion and positive full dataset from its Phase 3 RECOVER open-label extension (OLE) 1-year study evaluating brilaroxazine in patients with schizophrenia.
• Once-daily brilaroxazine demonstrated robust broad-spectrum efficacy that was sustained over 1-year across all major symptom domains of schizophrenia.
• The drug was generally well-tolerated, with a discontinuation rate of 35% in this long-term study, primarily due to withdrawal of consent (22%) and lost to follow up (7%), with only 1.1% due to treatment-related adverse events.
• Brilaroxazine improved multiple neuroinflammatory markers, which are reported to enhance efficacy and mitigate side effects.
• Key efficacy findings for pooled brilaroxazine doses (15, 30, and 50 mg) showed significant improvements from baseline to end of treatment (p < 0.001) in PANSS Total Score (-10.7 at 6-month, -18.1 at 12-month, -47.7 for rollover patients at 13-month), Positive Symptoms (-3.3, -5.0, -14.0), Negative Symptoms (-2.8, -4.4, -10.5), and Personal and Social Performance (4.5, 11.3, 32.7).
• Clinical Global Impression Severity (CGI-S) score showed >1-point improvement in 37.3% of patients at 6-month, 58.5% at 12-month, and 100% for rollover patients at 13-month.
• The safety profile was well-tolerated, with 8.5% of participants reporting at least one treatment-emergent adverse event (TEAE), mostly mild (6.5%) or moderate (2.0%) and transient.
• Most common TEAEs (≥2%) were headache (2.7%), insomnia (4.0%), sleep disturbance (2.9%), and mild tremor (3.1%).
• Brilaroxazine was not associated with clinically meaningful changes in movement disorder scales, cardiac, gastrointestinal, or drug-induced liver injury (DILI) side effects, nor significant changes in blood glucose levels.
• Patients experienced mild weight gain (1.52 kg pooled, 1.28 kg at 50 mg dose) and improved lipid and endocrine hormone levels (prolactin, thyroid).
• Long-term safety data from 100 patients completing 1-year of treatment meets a requirement for brilaroxazine's New Drug Application (NDA) submission to the U.S. Food and Drug Administration (FDA).

Sentiment

Score: 9

Explanation: The announcement is overwhelmingly positive, detailing successful completion of a Phase 3 open-label extension study with robust efficacy and a well-tolerated safety profile for brilaroxazine in schizophrenia. The results meet a key FDA NDA submission requirement and address significant unmet medical needs, indicating strong progress towards commercialization and potential for broad application.

Positives

• Robust broad-spectrum efficacy sustained over 1-year across all major symptom domains of schizophrenia, including negative symptoms.
• Generally well-tolerated safety profile with low rates of adverse events and discontinuation due to treatment-related AEs (1.1%).
• Significant improvements in PANSS Total Score, Positive Symptoms, Negative Symptoms, Social Cognition, Personal and Social Performance, and CGI-S scores.
• Improved multiple neuroinflammatory markers, potentially enhancing efficacy and mitigating side effects.
• No clinically meaningful changes in movement disorder scales (akathisia, extrapyramidal symptoms) over 1-year treatment.
• No drug-related serious adverse events (SAEs) or major safety concerns observed.
• No incidence of clinically significant cardiac side effects, gastrointestinal side effects, drug-induced liver injury (DILI), or significant change in blood glucose levels.
• Improved lipid levels and endocrine hormone levels (prolactin, thyroid).
• Long-term safety data from 100 patients completing 1-year of treatment fulfills a requirement for NDA submission to the U.S. FDA.
• Brilaroxazine has already received Orphan Drug Designation by the FDA for the treatment of Pulmonary Arterial Hypertension (PAH) and Idiopathic Pulmonary Fibrosis (IPF) conditions.
• Positive data from a clinical drug-drug interaction study showed no clinically significant interaction when combined with CYP3A4 inhibitors.

Negatives

• Mild weight gain (1.52 kg in the pooled dose group over 1-year treatment, with 1.28 kg at the 50 mg dose).
• Overall treatment discontinuation rate of 35% in the one-year study, although primarily due to withdrawal of consent (22%) and lost to follow up (7%) rather than adverse events.
• Most common treatment-emergent adverse events (TEAEs) included headache (2.7%), insomnia (4.0%), sleep disturbance (2.9%), and mild tremor (3.1%).

Risks

• Forward-looking statements are subject to known and unknown risks, uncertainties, and other factors that may cause actual results, performance, or achievements to be materially different from those expressed or implied.
• Such factors include those set forth in the Company's most recent Annual Report on Form 10-K for the fiscal year ended December 31, 2024, and other filings with the Securities and Exchange Commission.

Future Outlook

Reviva Pharmaceuticals intends to advance brilaroxazine's clinical program towards regulatory registration and aims to bring the therapy to more patients globally as quickly as possible. The company also plans to develop brilaroxazine for other neuropsychiatric indications, including bipolar disorder, major depressive disorder (MDD), and attention-deficit/hyperactivity disorder (ADHD). Additionally, brilaroxazine has shown promising nonclinical activity for inflammatory diseases such as psoriasis, pulmonary arterial hypertension (PAH), and idiopathic pulmonary fibrosis (IPF).

Management Comments

• Laxminarayan Bhat, Ph.D., Founder, President, and CEO of Reviva: "We are pleased to complete the positive registrational trial for our brilaroxazine program in schizophrenia and generate long-term data reinforcing brilaroxazines consistent, wide-spectrum efficacy, and well-tolerated safety profile. Importantly, the additional multiple biomarker data serve as independent measures of efficacy that further support improvements across all major symptom domains of schizophrenia. Our clinical program continues to advance towards registration, and we look forward to bringing brilaroxazine to more patients globally as fast as possible."
• Dr. Stephen R Marder, MD, Professor, Psychiatry and Biobehavioral Sciences at the University of California, Los Angeles: "Dissatisfaction with current standards of care is largely driven by persistent negative symptoms and poor functional outcomes. The robust improvement in negative symptoms and sustained broad-spectrum efficacy support the potential of brilaroxazine to address these unmet needs."
• Dr. Larry Ereshefsky, PharmD, BCPP, FCCP, Retired Professor of Psychiatry, Pharmacology and Psychiatry, The University of Texas: "Brilaroxazine improved multiple biomarkers including reduced levels of inflammatory cytokines that could contribute to enhanced efficacy and mitigate side effects. The impact of reduced inflammation on symptoms may result in improved patient adherence and clinical outcomes. The low discontinuation rates observed in the double-blind and OLE trials are consistent with this beneficial treatment profile."

Industry Context

The announcement highlights a significant advancement in the treatment of schizophrenia, a central nervous system (CNS) disorder with substantial unmet medical needs, particularly concerning persistent negative symptoms and functional outcomes. Brilaroxazine, a novel serotonin dopamine signaling modulator, addresses these challenges by demonstrating broad-spectrum efficacy and a favorable safety profile over a long term. The focus on improving neuroinflammatory markers aligns with emerging research in CNS diseases, suggesting a more comprehensive therapeutic approach. Reviva's strategy to expand brilaroxazine's development into other neuropsychiatric and inflammatory indications positions it as a versatile drug candidate with potential across multiple therapeutic areas, reflecting a trend towards leveraging drug mechanisms for broader applications.

Comparison to Industry Standards

• The robust improvement in negative symptoms and sustained broad-spectrum efficacy of brilaroxazine directly addresses a key area of dissatisfaction with current standards of care in schizophrenia, which often struggle with these persistent symptoms and poor functional outcomes.
• The low discontinuation rates observed in both the double-blind and OLE trials (1.1% due to treatment-related AEs in OLE) are consistent with a beneficial treatment profile, suggesting better tolerability compared to some existing therapies where side effects often lead to discontinuation.
• The document implies brilaroxazine's potential to improve patient adherence and clinical outcomes due to reduced inflammation and a favorable side effect profile, which are critical factors for long-term treatment success in chronic conditions like schizophrenia.

Stakeholder Impact

• Shareholders: The positive Phase 3 clinical trial results are highly likely to increase investor confidence and potentially the company's share price, signaling significant progress towards market approval and commercialization.
• Patients: Brilaroxazine offers the potential for a new, effective, and well-tolerated treatment option for schizophrenia, particularly addressing persistent negative symptoms and improving functional outcomes, which are significant unmet needs.
• Healthcare Providers: Provides a promising new therapeutic agent for managing schizophrenia, potentially offering a better safety and efficacy profile compared to existing treatments.
• Regulatory Authorities: The successful completion of the Phase 3 OLE study and meeting NDA requirements demonstrate the drug's potential for approval, moving it closer to market availability.
• Employees: Positive clinical outcomes can boost morale and provide job security, as the company progresses towards commercialization.

Next Steps

• Advance the brilaroxazine clinical program towards regulatory registration, including NDA submission to the U.S. FDA.
• Work towards bringing brilaroxazine to more patients globally as fast as possible.
• Develop brilaroxazine for other neuropsychiatric indications, including bipolar disorder, major depressive disorder (MDD), and attention-deficit/hyperactivity disorder (ADHD).
• Further explore brilaroxazine's promising nonclinical activity for inflammatory diseases such as psoriasis, pulmonary arterial hypertension (PAH), and idiopathic pulmonary fibrosis (IPF).

Key Dates

Recommendation

Keywords

Schizophrenia, Brilaroxazine, Phase 3 RECOVER OLE, Clinical Trial Results, Reviva Pharmaceuticals, CNS Disorders, Neuropsychiatric, Serotonin Dopamine Modulator, Drug Development, Biopharmaceutical, FDA Submission, Orphan Drug Designation