brilaroxazine (RP5063) / Reviva - LARVOL DELTA

Advances in schizophrenia research and treatment: exploring neurotransmitter imbalances, genetics, and innovative therapies. (PubMed, Prog Neuropsychopharmacol Biol Psychiatry) - "Recently, the antipsychotics lumateperone and xanomeline-trospium were approved. Iclepertin, ralmitaront, roluperidone, and brilaroxazine are molecules in Phase 2 or 3 clinical trials...Adjuvant treatments aimed at mitigating neuroinflammation and oxidative stress; microbiome-targeted interventions, neuroprotective and metabolic agents are being explored. Current research efforts aim to improve treatment outcomes by addressing gaps in antipsychotic therapy and mitigating its adverse effects."

Journal • Review • CNS Disorders • Cognitive Disorders • Inflammation • Mental Retardation • Psychiatry • Schizophrenia

European Patent (EP3749324) granted by the European Patent Office (EPO) in November 2025, covering use of brilaroxazine for the treatment of pulmonary fibrosis, including idiopathic pulmonary fibrosis (IPF), adding to Reviva’s existing patent protection in key markets around the world including the United States, China and Japan. (The Manila Times)

Patent • Idiopathic Pulmonary Fibrosis

New Pharmacological Treatment Approaches for Schizophrenia: Navigating the Post-iclepertin Landscape. (PubMed, CNS Drugs) - "The most compelling therapeutic approaches continue to be serotonin-dopamine activity modulators (brilaroxazine) and emerging M4 selective agonists (NBI-1117568). While iclepertin's discontinuation represents a significant setback for GlyT1 inhibition strategies, the approval of KarXT and advancing pipeline candidates offer potential for therapeutic advances. Critical challenges include escalating placebo responses that compromise trial assay sensitivity, underscoring the need for improved patient stratification, refined trial methodology, and outcome measures that accurately capture real-world benefit."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Mental Retardation • Psychiatry • Schizophrenia • DRD2

Reviva Announces Regulatory Update Regarding the Development of Brilaroxazine for the Treatment of Schizophrenia (The Manila Times) - "In written feedback, the FDA recommended a second Phase 3 clinical trial for brilaroxazine in patients with schizophrenia to, among other things, generate additional efficacy data and expand the safety dataset. Subject to sufficient financing, Reviva plans to initiate the RECOVER-2 Phase 3 trial in the first half of 2026....The recommendation follows FDA review of the Company’s existing nonclinical and clinical data package, including two completed randomized, double-blind, placebo-controlled, multicenter clinical trials (one Phase 2 trial and one Phase 3 trial that included a 1-year open label extension) and clinical pharmacology studies designed to support a potential NDA filing."

FDA event • New P3 trial • Schizophrenia

A single, interpretable vocal biomarker for enriching antipsychotic clinical trials. (PubMed, Biol Psychiatry) - "Speech latency is a face-valid, objective biomarker derived from standard clinical assessments. As an enrichment tool, it reduced sample-size needs and enhanced outcomes. This has important implications for reducing clinical trial costs and burden."

Biomarker • Clinical • Journal • CNS Disorders • Psychiatry • Schizophrenia

Brilaroxazine treatment effects on BDNF and inflammatory cytokines in schizophrenia: RECOVER trial in acute and stable patients over 1 year (Neuroscience 2025) - "These improvements likely contributed to brilaroxazine's sustained efficacy over 1 year, particularly for negative symptoms, and safety profile. These effects hold promise for treatment-resistant schizophrenia patients."

Clinical • Late-breaking abstract • CNS Disorders • Psychiatry • Schizophrenia • BDNF • CXCL8 • IFNG • IL10 • IL6 • TNFA

Reviva to Present Anti-Inflammatory Impacts of Brilaroxazine in Schizophrenia from the RECOVER 12-month Open Label Extension Trial at Neuroscience 2025 (The Manila Times)

P3 data • Schizophrenia

Anticipated Milestones and Events (GlobeNewswire) - "Investigational new drug application (IND) submission for liposomal-gel formulation of brilaroxazine in psoriasis expected by H2-2026."

IND • Psoriasis

Reviva...today announced European Patent 3749324 has been granted by the European Patent Office (EPO) covering use of brilaroxazine for the treatment of pulmonary fibrosis, including idiopathic pulmonary fibrosis (IPF)... (GlobeNewswire)

Patent • Idiopathic Pulmonary Fibrosis

Anticipated Milestones and Events (Reviva Press Release) - "Planned meeting with FDA to discuss brilaroxazine’s path to approval in Q4 2025; Potential NDA submission for brilaroxazine in schizophrenia targeted in Q2 2026; Plans are being assessed to initiate a potential registrational Phase 3 RECOVER-2 trial evaluating brilaroxazine for the treatment of schizophrenia pending FDA recommendation for a path to approval; Investigational new drug application (IND) submission for liposomal-gel formulation of brilaroxazine in psoriasis expected by Q2- 2026"

FDA filing • IND • New P3 trial • Psoriasis • Schizophrenia

Open Label Phase 3 Study of Brilaroxazine for Schizophrenia Shows Efficacy, Tolerability (Psychiatric Times) - P3 | N=690 | RECOVER (NCT05184335) | Sponsor: Reviva Pharmaceuticals | "According to Reviva, the data for brilaroxazine, a novel serotonin dopamine signaling modulator with demonstrated selectivity for other receptors, showed “robust broad-spectrum efficacy that was sustained over 1-year and was generally well tolerated with a discontinuation rate of 35% in this long-term study...In addition, the RECOVER trial found brilaroxazine had a well-tolerated safety profile across the 3 doses, with only 8.5% of participants reporting at least 1 treatment adverse event."

P3 data • Schizophrenia

Reviva Reports First Quarter 2025 Financial Results and Recent Business Highlights (GlobeNewswire) - "Anticipated Milestones and Events: (i) Full data analysis of the OLE trial including long-term safety, tolerability and efficacy, as well as vocal and blood biomarker data expected in Q2 2025; (ii) Initiation of registrational Phase 3 RECOVER-2 trial evaluating brilaroxazine for the treatment of schizophrenia expected in mid-2025, subject to receipt of additional financing; (iii) Potential NDA submission for brilaroxazine in schizophrenia targeted for the fourth quarter of 2026 Investigational new drug application (IND) submission for liposomal-gel formulation of brilaroxazine in psoriasis expected later in 2025."

FDA filing • IND • New P3 trial • P3 data • Psoriasis • Schizophrenia

Reviva to Present Late-Breaking Poster on the RECOVER Long-term Open Label Extension Trial for Brilaroxazine in Schizophrenia at the 2025 ASCP Annual Meeting (GlobeNewswire) - "Reviva Pharmaceuticals Holdings, Inc...today announced that Laxminarayan Bhat, Ph.D., Founder, President, and CEO of Reviva will present a late-breaking poster presentation on the RECOVER 12-month open label extension trial for brilaroxazine in schizophrenia at the 2025 American Society of Clinical Psychopharmacology (ASCP) annual meeting, taking place May 27-30, 2025, in Scottsdale, AZ."

Late-breaking abstract • P3 data • Schizophrenia

Unlocking the potential of lumateperone and novel anti-psychotics for schizophrenia. (PubMed, Bioimpacts) - "This review also focuses on a few more emerging antipsychotics like brexpiprazole, brilaroxazine, roluperidone, F17464, pimavanserin (ACP-103), xanomeline, BI 409306, BI 425809 and MK-8189 which are under different phase of clinical trials and might get approved soon. All the antipsychotic drugs covered did not show any other severe adverse effects except gastrointestinal issues and cardiometabolic risk factors. However, still rigorous clinical trials and modifications are needed to manage adverse effects, and we can expect a few antipsychotics to be on the market soon."

Journal • Review • Anesthesia • CNS Disorders • Constipation • Fatigue • Gastroenterology • Gastrointestinal Disorder • Psychiatry • Schizophrenia

Reviva Reports Full Year 2024 Financial Results and Recent Business Highlights (GlobeNewswire) - "Full data analysis of the OLE trial including long-term safety, tolerability and efficacy, as well as vocal and blood biomarker data expected in Q2 2025. Initiation of registrational Phase 3 RECOVER-2 trial evaluating brilaroxazine for the treatment of schizophrenia expected in mid-2025, subject to receipt of additional financing. Potential NDA submission for brilaroxazine in schizophrenia targeted for the fourth quarter of 2026. Investigational new drug application (IND) submission for liposomal-gel formulation of brilaroxazine in psoriasis expected later in 2025."

FDA filing • IND • New P3 trial • P3 data • Psoriasis • Schizophrenia

Reviva to Present Brilaroxazine Topline Data for Long-Term OLE Portion of RECOVER Study in Schizophrenia at 2025 SIRS Congress (GlobeNewswire) - "Reviva Pharmaceuticals Holdings, Inc...announced today topline data from the long-term open label extension portion of the Phase 3 RECOVER study evaluating brilaroxazine in schizophrenia will be presented as part of an oral presentation at the 2025 Congress of the Schizophrenia International Research Society (SIRS) taking place March 29 to April 2, 2025 in Chicago, Illinois, U.S."

P3 data: top line • Schizophrenia

The effect of dynamic visual acuity on rapid naming in school-aged children with dyslexia. (PubMed, Int J Pediatr Otorhinolaryngol) - "Children with dyslexia had lower dynamic visual acuity, and girls were more markedly affected. In addition, a moderately negative association was observed between dynamic visual acuity and rapid naming time in children with dyslexia."

Journal

RECOVER: Safety and Efficacy of Brilaroxazine (RP5063) in Schizophrenia (clinicaltrials.gov) - P3 | N=690 | Recruiting | Sponsor: Reviva Pharmaceuticals | N=402 ➔ 690 | Trial completion date: Oct 2024 ➔ Feb 2025 | Trial primary completion date: Oct 2024 ➔ Feb 2025

Enrollment change • Trial completion date • Trial primary completion date • CNS Disorders • Psychiatry • Schizophrenia

Utilizing Caenorhabditis Elegans as an Experimental Model to Predict the Effects of Brilaroxazine Compared to Established Antipsychotics (ASHP 2024) - No abstract available

CNS Disorders

Reviva Announces Grant of U.S. Patent Covering Use of Brilaroxazine for the Treatment of Idiopathic Pulmonary Fibrosis (GlobeNewswire) - "Reviva Pharmaceuticals Holdings, Inc...announced United States (U.S.) Patent 12053477 has been granted by the U.S. Patent and Trademark Office (USPTO) covering use of brilaroxazine for the treatment of idiopathic pulmonary fibrosis (IPF), and for the treatment of pulmonary fibrosis in a subject having chronic obstructive pulmonary disease (COPD), sickle cell anemia, scleroderma, or lung cancer, adding to its existing patent protection in key market Japan. Brilaroxazine has received Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) for the treatment of IPF."

Patent • Idiopathic Pulmonary Fibrosis • Pulmonary Disease

Effectiveness of Brilaroxazine on Functional and Underlying Pathological Inflammation and Fibrosis Parameters in a Bleomycin-induced Idiopathic Pulmonary Fibrosis Model Using Male Sprague Dawley Rats (ATS 2024) - "Rationale: The pathology of idiopathic pulmonary fibrosis (IPF), a chronic, progressive, and debilitating lung disease with chronic alveolar inflammation and fibrosis, involves increased pulmonary serotonin (5-HT) 2A/2B/7 receptor expression. Brilaroxazine intervention attenuated the effects of BLM induction on multiple parameters, notably body weight, lung weight, and hydroxyproline levels. It exhibited a considerable reduction in both fibrosis score and collagen accumulation. Brilaroxazine's effects appeared like SB-269970 and nintedanib."

Late-breaking abstract • Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • COL1A1 • TGFB1

Reviva Announces Enrollment Update for Open Label Extension Study Evaluating Brilaroxazine in Schizophrenia (GlobeNewswire) - "RECOVER Trial OLE Enrollment Status Update As of May 15, 2024: Trial progressing as expected in the USA, Europe (Bulgaria) and Asia (India); 358 patients enrolled in the study; 223 patients currently on treatment in the study; Over 130 patients currently in the study have completed 1-6 months of treatment; Over 90 patients currently in the study have completed 6-9 months of treatment; 23 patients have completed 12 months of treatment; Long-term safety data from 100 patients who have completed 12 months of treatment is a requirement for brilaroxazine’s NDA submission to the FDA; Reviva is on track to complete the 12 months long-term safety study in Q4 2024."

Trial status • CNS Disorders • Schizophrenia

Reviva to Present New Preclinical Efficacy Data on Brilaroxazine in Idiopathic Pulmonary Fibrosis at 2024 ATS International Conference (GlobeNewswire) - "Reviva Pharmaceuticals Holdings, Inc...announced that Laxminarayan Bhat, Ph.D., Founder, President, and CEO of Reviva, will present new efficacy data on brilaroxazine in an animal model of idiopathic pulmonary fibrosis as part of a late-breaking poster presentation at the 2024 American Thoracic Society (ATS) International Conference, to be held in San Diego, CA, May 17-22, 2024."

Preclinical • Idiopathic Pulmonary Fibrosis • Pulmonary Disease

Reviva Announces FDA Alignment on Brilaroxazine Clinical Trials for NDA in Schizophrenia (GlobeNewswire) - "Reviva Pharmaceuticals Holdings, Inc...announced today it has gained alignment with the U.S. Food and Drug Administration (FDA) on its registrational Phase 3 program for brilaroxazine in schizophrenia....'Importantly, we have already successfully completed and announced the results of our pivotal Phase 3 RECOVER trial in October 2023, and we are set to initiate our RECOVER-2 trial during this quarter. We expect topline data from our 1-year OLE trial in the fourth quarter of this year. Collectively, we expect to have completed all of the outlined NDA submission requirements by the third quarter of 2025.'"

NDA • New P3 trial • P3 data: top line • CNS Disorders • Schizophrenia

Brilaroxazine Phase 3 Recover Trial in Acute Schizophrenia Supports Efficacy, Safety, and Effects on Neuroinflammation (SIRS 2024) - "Brilaroxazine 50 mg produced a 10.1-point greater reduction vs. placebo (-23.9 vs. -13.8, p <0.001) for the primary study endpoint, PANSS total score."

Clinical • P3 data • CNS Disorders • Schizophrenia • CXCL8 • IL6