Ohtuvayre (ensifentrine nebulized) / Ligand, Nuance Biotech, Merck (MSD) - LARVOL DELTA

A Phase II Study to Assess the Pharmacokinetics, Pharmacodynamics, and Safety of Single Inhaled Doses of Ensifentrine-glycopyrrolate Fixed Dose Combination, Ensifentrine, and Glycopyrrolate in Subjects With Chronic Obstructive Pulmonary Disease (clinicaltrials.gov) - P2 | N=33 | Completed | Sponsor: Verona Pharma plc | Active, not recruiting ➔ Completed

Trial completion • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Advancing COPD management through novel pharmacological agents: ensifentrine and dupilumab. (PubMed, Breathe (Sheff)) - "By focusing on disease endotypes, these novel therapies underscore the growing role of personalised treatment approaches in COPD. Continued investigation into biomarkers and long-term outcomes will be essential for integrating these therapies into routine clinical practice."

Journal • Review • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • IL13 • IL4

Evaluation of Performance of Daily Nebulization of Ensifentrine via Mesh Nebulizer (ASHP 2025) - No abstract available

Ensifentrine: A Potential Shift in COPD Management. (PubMed, J Pak Med Assoc) - No abstract available

Journal • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Bronchiectasis Treatment Goals, Unmet Needs, and Emerging Therapies: A Podcast. (PubMed, Pulm Ther) - "In the phase 3, 52-week ASPEN trial, brensocatib significantly reduced exacerbation burden, and the 25-mg dose reduced lung function decline and nominally significantly improved patient-reported symptoms compared with placebo. Additional therapies in development include other DPP1 inhibitors (verducatib and HSK31858) and drugs targeting phosphodiesterase 3/4 inhibition (ensifentrine) and anti-interleukin-33 (itepekimab). Overall, the future is promising for patients with the historically neglected and underdiagnosed disease bronchiectasis, with growing awareness and new therapeutic tools becoming available. Podcast (MP4 81554 KB)."

Journal • Bronchiectasis • Genetic Disorders • Immunology • Infectious Disease • Inflammation • Non‐Cystic Fibrosis Bronchiectasis • Pediatrics • Pulmonary Disease • Respiratory Diseases • IL33

Estimating the Value of Ensifentrine in Addition to Background Maintenance Therapy for the Treatment of Chronic Obstructive Pulmonary Disease. (PubMed, Forum Health Econ Policy) - "Stacked cohorts with dynamic pricing increases VBPs by 86-170 %. When including GCEA elements and adjustments to better reflect real-world COPD clinical pathways, ensifentrine + BMT is cost-effective below an annual price of $61,000 at a willingness-to-pay of $150,000 per quality-adjusted life-year."

Journal • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Merck has withdrawn the European Union marketing application for Ohtuvayre, the chronic obstructive pulmonary disease treatment it recently acquired through its $10 billion purchase of Verona Pharma. (AD HOC NEWS) - "Merck formally pulled the EU marketing authorization application on October 30, 2025—a mere three weeks after completing the massive Verona Pharma takeover on October 7. The European Medicines Agency has confirmed the termination of the review process. Company representatives attributed this move to an ongoing 'portfolio priority assessment.'...While European plans have been shelved, Ohtuvayre continues to demonstrate promising commercial performance in the United States...$71.3 million in net sales during the first quarter of 2025"

European regulatory • Sales • Chronic Obstructive Pulmonary Disease

Verona Pharma Ireland Limited withdrew its application for a marketing authorisation of Ohtuvayre for the treatment of chronic obstructive pulmonary disease (COPD). (European Medicines Agency) - "The company withdrew the application on 30 October 2025."

European regulatory • Chronic Obstructive Pulmonary Disease

Anti-oxidative and anti-inflammatory effects of the phosphodiesterase 3/4 inhibitor ensifentrine. (PubMed, Int Immunopharmacol) - "Peripheral blood mononuclear cells (PBMCs) from COPD patients and healthy controls and human bronchial epithelial cells were treated with ensifentrine or a PDE4 inhibitor (roflumilast or GSK256066) or dexamethasone prior to exposure to lipopolysaccharide or T-cell receptor activation, with measurement of supernatant levels of TNFα and IFNγ, respectively. We report a novel mechanism of action for ensifentrine, reducing effects of oxidative stress through a PDE3 dependent mechanism. The anti-inflammatory effects of ensifentrine were lower compared to the PDE4 inhibitors tested."

IO biomarker • Journal • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • CASP3 • CASP7 • IFNG • TNFA

Novel Maintenance Therapies for Chronic Obstructive Pulmonary Disorder. (PubMed, Ann Pharmacother) - "Evidence supports LABA/LAMA with nuanced use of ICS. Several novel therapies are approved or are being studied for patients suboptimally controlled. Pharmacists can assist in medication optimization and access; however, patient-specific factors like exacerbation history, blood eosinophils, and COPD endotype must be considered. Implementing early identification screening tools such as CAPTURE should factor into patient assessment."

Journal • Review • Chronic Obstructive Pulmonary Disease • Immunology • Infectious Disease • Pneumococcal Infections • Pulmonary Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

Pharmacological management of COPD. (PubMed, Presse Med) - "The positive clinical trial results for dupilumab (a monoclonal antibody directed against the shared IL-4 and IL-13 receptor) and ensifentrine (an inhibitor of phosphodiesterase 3 and 4) represent significant advances in the pharmacological management of COPD. This review describes the recent progress in COPD pharmacology, covering novel molecules, new evidence and changes in clinical practice."

Journal • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases • IL13 • IL4

1118: COPD Management: Advanced Pharmacological Options (CHEST 2025) - "This session will address medication class selection in COPD highlighting considerations for newly approved options (ensifentrine and dupilumab) and how they fit in with existing therapies. Review the evidence for ensifentrine, roflumilast, and azithromycin and provide a framework for drug selection 3. Learn about the currently available and emerging biologic therapeutics in the management of COPD"

Metastases • Chronic Obstructive Pulmonary Disease • Eosinophilia • Immunology • Respiratory Diseases

APPROACH TO A GROWING LANDSCAPE OF PHARMACOLOGIC THERAPIES FOR COPD PATIENTS WITH HIGH EXACERBATION RISK (CHEST 2025) - "It has been shown that ensifentrine, dupilumab, long-term azithromycin, and roflumilast all help to reduce exacerbations in patients prone COPD exacerbations 1 . Ensifentrine or dupilumab was an appropriate choice for over half of this cohort; these medications have expanded the options for treating Group E COPD patients at risk for recurrent exacerbations. With a growing landscape of pharmacologic options to help reduce the risk of COPD exacerbations, it is important for patients with high exacerbation risk be continually evaluated for additional therapies. Based on the data from this cohort, the majority of patients hospitalized due AECOPD would benefit from an additional pharmacologic agent with their optimized inhaled therapies."

Clinical • Asthma • Chronic Obstructive Pulmonary Disease • Immunology • Respiratory Diseases

EFFICACY OF ENSIFENTRINE IN PATIENTS WITH A HISTORY OF COPD EXACERBATIONS AND EOSINOPHILS LESS THAN 300 CELLS/µL (CHEST 2025) - "PURPOSE: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2025 report recommends adding dupilumab to the combination of an inhaled corticosteroid, long-acting beta agonist, and long-acting muscarinic antagonist in COPD patients who continue to exacerbate if blood eosinophil levels are $300 cells/μL. Ensifentrine improved lung function, symptoms, and quality of life and reduced exacerbation rate and risk in patients with recent exacerbation history and eosinophils <300 cells/μL. Although not statistically significant, the reduction in the rate and risk of moderate/severe exacerbations observed in this subgroup is consistent with the magnitude of effect observed in these parameters in the overall ENHANCE population. CLINICAL IMPLICATIONS: Ensifentrine provides a novel mechanism of action for clinically meaningful improvements in lung function, symptoms and quality of life, and reduction in exacerbations in patients with a recent exacerbation and..."

Clinical • Chronic Obstructive Pulmonary Disease • Immunology • Respiratory Diseases

ENSIFENTRINE IMPROVED LUNG FUNCTION, SYMPTOMS, QUALITY OF LIFE, AND EXACERBATION RATE AND RISK REGARDLESS OF SEX (CHEST 2025) - "Ensifentrine improved lung function, symptoms, and quality of life and reduced exacerbation rate and risk in both males and females in the ENHANCE trials. CLINICAL IMPLICATIONS: Sex-differences in COPD can affect disease mechanisms, airway structures, symptoms, and treatment responses. Ensifentrine, a novel agent with dual bronchodilator and anti-inflammatory action, provides clinical benefit including improvement in lung function, symptoms, and quality of life in a broad population of patients with moderate-to- severe COPD regardless of patient sex."

HEOR • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

CHEST 2025: Ensifentrine Boosts Quality of Life in COPD (EMJ Reviews) - "The post hoc analysis evaluated 1,384 patients over twenty four weeks, comparing ensifentrine with placebo....Benefits extended to respiratory symptoms captured by the Evaluating Respiratory Symptoms total score at weeks six, twelve, and twenty four. More patients on ensifentrine met the responder threshold of at least a two point reduction at weeks six and twelve, with a numerical advantage maintained at week twenty four. Health related quality of life, assessed by the St. George’s Respiratory Questionnaire, improved with ensifentrine at all measured visits and reached significance at weeks six and twelve."

Retrospective data • Chronic Obstructive Pulmonary Disease • Immunology

ENSIFENTRINE IMPROVED LUNG FUNCTION, SYMPTOMS, AND QUALITY OF LIFE REGARDLESS OF EXACERBATION HISTORY (CHEST 2025) - "In patients with moderate-to-severe COPD, ensifentrine significantly improved lung function, as measured by Week 12 average FEV 1 AUC 0-12h and peak FEV 1 at Week 12, in patients with and without a history of exacerbation within 15 months of screening. Ensifentrine also provided early and sustained improvements in symptoms, dyspnea, and quality of life regardless of baseline exacerbation history. CLINICAL IMPLICATIONS: Ensifentrine provides a novel mechanism of action with dual bronchodilator and anti- inflammatory effects which improves lung function and symptom control in COPD patients with and without recent history of COPD exacerbations."

HEOR • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

ENSIFENTRINE IMPROVED SLEEP IN PATIENTS WITH MODERATE-TO-SEVERE COPD IN THE PHASE 3 ENHANCE TRIALS (CHEST 2025) - "Treatment with nebulized ensifentrine provided early and sustained reductions in sleep disturbance in both ENHANCE trials that were statistically significant in the pooled ENHANCE population. CLINICAL IMPLICATIONS: Many patients with COPD are impacted by significant sleep disturbances from respiratory symptoms. Ensifentrine provides early and sustained improvements in sleep for these patients which may be from improvement in COPD symptoms."

Clinical • P3 data • Chronic Obstructive Pulmonary Disease • CNS Disorders • Cough • Fatigue • Immunology • Respiratory Diseases • Sleep Disorder

Bridging Clinical Evidence and Practice: The Role of Ensifentrine in COPD Treatment – Asthma and COPD Section (CHEST 2025) - No abstract available

Clinical • Asthma • Chronic Obstructive Pulmonary Disease • Immunology • Respiratory Diseases

7818: Bridging Clinical Evidence and Practice: The Role of Ensifentrine in COPD Treatment – Asthma and COPD Section (CHEST 2025) - "Additionally, this session will evaluate strategies to integrate ensifentrine and explore barriers to implementation while synthesizing clinical evidence with experiential insights from outpatient care settings. Through this comprehensive approach, the session aims to foster critical thinking and collaborative dialogue on how to optimize therapeutic outcomes using ensifentrine, ultimately improving patient-centered care in COPD management."

Clinical • Asthma • Chronic Obstructive Pulmonary Disease • Immunology • Respiratory Diseases

A Phase II Study to Assess the Pharmacokinetics, Pharmacodynamics, and Safety of Single Inhaled Doses of Ensifentrine-glycopyrrolate Fixed Dose Combination, Ensifentrine, and Glycopyrrolate in Subjects With Chronic Obstructive Pulmonary Disease (clinicaltrials.gov) - P2 | N=33 | Active, not recruiting | Sponsor: Verona Pharma plc | Recruiting ➔ Active, not recruiting

Enrollment closed • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

ENSIFENTRINE IMPROVED SYMPTOMS, DYSPNEA, AND QUALITY OF LIFE IN PATIENTS WITH COPD WHO DID NOT EXACERBATE DURING THE ENHANCE TRIALS (CHEST 2025) - "Ensifentrine produced early and sustained improvements in symptoms, including dyspnea, and quality of life measures in patients with moderate-to-severe COPD who did not experience an exacerbation during the ENHANCE trials. CLINICAL IMPLICATIONS: Patients with COPD continue to suffer from daily symptoms and impaired quality of life. Ensifentrine provides clinically meaningful improvements in symptoms, including dyspnea, and quality of life for patients with COPD, even in those who are not experiencing exacerbations."

Clinical • HEOR • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Merck Completes Acquisition of Verona Pharma (Businesswire) - "Through this acquisition Merck has added Ohtuvayre (ensifentrine), a first-in-class selective dual inhibitor of phosphodiesterase 3 and 4 (PDE3 and PDE4), to its growing cardio-pulmonary pipeline and portfolio....Under the terms of the acquisition agreement, Merck, through a subsidiary, has acquired all outstanding shares of Verona Pharma for $107 per ADS, each of which represents eight Verona Pharma ordinary shares, for a total transaction value of approximately $10 billion."

M&A • Chronic Obstructive Pulmonary Disease • Immunology

Hydrophobic interaction-driven binding of ensifentrine stabilizes PDE3A: insights from X-ray crystallography and molecular dynamics. (PubMed, Phys Chem Chem Phys) - "These multi-scale structural and dynamic insights provide the first comprehensive molecular picture of the PDE3A-ensifentrine interaction and guide future designs for selective phosphodiesterase inhibitors and synergistic bronchodilator therapies. Notably, this study highlights the potential for improving PDE3A selectivity and designing more effective and selective inhibitors for COPD and other respiratory conditions."

Journal • Cardiovascular • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • PDE3A

The effect of ensifentrine on lung function and exacerbations in patients with COPD according to baseline dyspnea (ERS 2025) - "Significant improvements in lung function and reduction in the rate and risk of moderate/severe exacerbations were demonstrated with ensifentrine, regardless of baseline mMRC. These findings support the use of ensifentrine in a broad population of patients with moderate to severe COPD."

Clinical • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases