brilaroxazine (RP5063) / Reviva - LARVOL DELTA

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

Brilaroxazine lipogel displays antipsoriatic activity in imiquimod-induced mouse model. (PubMed, Skin Res Technol) - "Brilaroxazine Lipogel displayed significant activity in imiquimod-induced psoriatic animals, offering a novel therapeutic strategy."

Journal • Preclinical • Dermatology • Dermatopathology • Immunology • Psoriasis • TGFB1 • TNFA

RECOVER: Safety and Efficacy of Brilaroxazine (RP5063) in Schizophrenia (clinicaltrials.gov) - P3 | N=402 | Recruiting | Sponsor: Reviva Pharmaceuticals | Trial completion date: Dec 2023 ➔ Oct 2024 | Trial primary completion date: Dec 2023 ➔ Oct 2024

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

Reviva Announces $30 Million Registered Direct Offering Priced At-the-Market Under Nasdaq Rules (BioSpace) - "Reviva Pharmaceuticals Holdings, Inc...announced that it has entered into definitive agreements with several healthcare-focused institutional investors, and an investment vehicle managed by a firm affiliated with a member of the Company’s Board of Directors, for the sale and issuance of 5,853,660 shares of the Company’s common stock (or prefunded warrants in lieu thereof) and warrants to purchase up to 5,853,660 shares of common stock at a combined offering price of $5.125 per share of common stock (or prefunded warrant in lieu thereof) and accompanying warrant in a registered direct offering priced at-the-market under the Nasdaq rules....Reviva intends to use the net proceeds from this offering, together with its existing cash and cash equivalents, to fund research and development activities, including the registrational Phase 3 RECOVER-2 trial and other clinical and regulatory development..."

Commercial • CNS Disorders • Schizophrenia

Novel Compounds in the Treatment of Schizophrenia-A Selective Review. (PubMed, Brain Sci) - "We discuss ten novel drugs, three of which have been approved by the FDA (Olanzapine/Samidorphan, Lumateperone, and Pimavanserin). The rest are under clinical trial investigation (Brilaroxazine, Xanomeline/Trospium, Emraclidine, Ulotaront, Sodium Benzoate, Luvadaxistat, and Iclepertin). However, additional basic and clinical research is required not only to improve our understanding of the neurobiology and the potential novel targets in the treatment of schizophrenia, but also to establish more effective therapeutical interventions for the syndrome, including the attenuation of negative and cognitive symptoms and avoiding dopamine blockade-related adverse effects."

Journal • Review • CNS Disorders • Psychiatry • Schizophrenia

Reviva Pharmaceuticals Announces 80% Global Enrollment Update for Pivotal Phase 3 RECOVER Study Evaluating Brilaroxazine for Schizophrenia (GlobeNewswire) - "Reviva Pharmaceuticals...today announced over 80% of patients have been enrolled in the pivotal Phase 3 RECOVER study evaluating brilaroxazine for the treatment of schizophrenia. Enrollment is ongoing at multiple sites in the United States, Europe, and Asia....'We believe the multifaceted activity of brilaroxazine offers the differentiated potential to improve behavioral symptoms as well as the accompanying neuroinflammation and comorbid symptoms commonly associated with schizophrenia. We believe that brilaroxazine’s compelling pharmacological and safety profile has potential to be a well-tolerated treatment approach for the estimated 24 million people worldwide suffering from schizophrenia. We look forward to reporting topline Phase 3 data in Q3 2023.'"

P3 data: top line • Trial status • CNS Disorders • Schizophrenia

Brilaroxazine Efficacy in a Bleomycin-induced Rodent Model of Idiopathic Pulmonary Fibrosis (ATS 2023) - "Brilaroxazine intervention effectively impacted survival, functional, histologic, and pathophysiological parameters in the BLM-induced model. Both interventions significantly affected survival and markers of inflammation and extracellular deposition. D1 exerted significant effects across a broad array of parameters."

Late-breaking abstract • Preclinical • Cardiovascular • Fibrosis • Hypertension • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • IL6

Reviva Pharmaceuticals Announced Preclinical Efficacy Data on Brilaroxazine in IPF at the 2023 American Thoracic Society International Conference and Publication in Medical Research Archives (GlobeNewswire) - "Reviva Pharmaceuticals...has presented preclinical data on the novel serotonin-dopamine modulator brilaroxazine in idiopathic pulmonary fibrosis (IPF) at the 2023 American Thoracic Society (ATS) International Conference which took place in Washington, DC, USA, May 19-24, 2023. The Company also announced acceptance of this data for publication in Medical Research Archives....'This preclinical evaluation in IPF provides proof-of-concept support for the potential of brilaroxazine to treat pulmonary fibrosis and inflammation stemming from underlying dysfunction in serotonin signaling in the lung. Brilaroxazine has already received Orphan Drug Designation by the U.S. FDA for IPF.'"

Orphan drug • Preclinical • Idiopathic Pulmonary Fibrosis • Interstitial Lung Disease

Reviva Pharmaceuticals Announces Presentation of Clinical Pharmacology Studies Data on Brilaroxazine at the ASPET 2023 Annual Meeting (GlobeNewswire) - "Reviva Pharmaceuticals...as presented two posters on promising clinical pharmacology and safety studies data on the novel serotonin-dopamine stabilizer brilaroxazine at the American Society for Pharmacology and Experimental Therapeutics (ASPET) 2023 annual meeting took place in St. Louis, Missouri, USA, May 18-21, 2023. The ASPET posters are available at revivapharma.com/publications. Brilaroxazine is currently in phase 3 clinical trials for schizophrenia and topline data from the pivotal phase 3 is anticipated in mid this year....CYP3A inhibition and induction exert limited effects on brilaroxazine pharmacokinetics...Brilaroxazine’s predictable PK profile with daily doses up to 100 mg allowing for once daily dosing has been defined in clinical studies....As part of the required studies for New Drug Application (NDA), brilaroxazine’s single-dose pharmacokinetics, metabolism, and excretion (PME) profiles were evaluated in humans and animals."

P3 data • Preclinical • CNS Disorders • Schizophrenia

Reviva Reports First Quarter 2023 Financial Results and Recent Business Highlights (GlobeNewswire) - "Topline data for pivotal Phase 3 RECOVER trial evaluating brilaroxazine for the treatment of schizophrenia anticipated in mid-2023. May initiate Phase 2a studies in bipolar disorder, major depressive disorder, and attention deficit hyperactive disorder in second half 2023, subject to the receipt of additional financing. Submit investigational new drug application (IND) for liposomal-gel formulation of brilaroxazine in psoriasis expected in 2024."

IND • New P2a trial • P3 data: top line • Bipolar Disorder • CNS Disorders • Depression • Major Depressive Disorder • Psoriasis • Schizophrenia

Brilaroxazine topical liposomal-gel formulation displays efficacy in the imiquimodinduced psoriatic BALB/c mouse model (ISID 2023) - "Brilaroxazine Lipogeldisplayed significant activity in imiquimod-induced psoriatic animals, offering a noveltherapeutic strategy."

Late-breaking abstract • Preclinical • Dermatology • Dermatopathology • Fibrosis • Immunology • Psoriasis • CXCL8 • IFNG • IL1B • IL6 • TGFB1 • TNFA