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

Post-marketing safety of ensifentrine in COPD: A retrospective pharmacovigilance study using disproportionality analysis of FAERS/AEMS reports. (PubMed, Medicine (Baltimore)) - "Respiratory reporting patterns predominated in early post-marketing reports for ensifentrine. These findings should be interpreted as hypothesis-generating pharmacovigilance signals rather than estimates of incidence or causality."

Adverse events • Journal • P4 data • Retrospective data • Cardiovascular • Chronic Obstructive Pulmonary Disease • Immunology • Psychiatry • Pulmonary Disease • Respiratory Diseases

Updates in COPD Management: From Inflammatory Pathways to Targeted Therapies. (PubMed, Eur J Clin Invest) - "COPD management is evolving toward precision medicine, guided by inflammatory phenotypes, biomarkers, and individualised risk profiles. Continued investigation into targeted biologics, anti-inflammatory agents, and incorporating biomarkers into clinical practice may improve outcomes and reduce disease burden."

Biomarker • Journal • Review • Cardiovascular • Chronic Obstructive Pulmonary Disease • Cognitive Disorders • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • IL33

2250: Practice-Changing Research in COPD, Presented by CHEST® Journal (CHEST 2026) - "This session will review an investigation into the impact of ensifentrine on COPD exacerbations; an exploration of clinical tools to improve risk stratification for patients at risk of major adverse cardiovascular events; and an update on the findings of a 2025 examination of the effect of dupilumab on health-related quality of life and respiratory symptoms in patients with COPD and type 2 inflammation. 3. Review updates to recent research into the effect of dupilumab on health-related quality of life and respiratory symptoms in patients with COPD."

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

Integrating Disease Burden and Cost-Effectiveness for Value-Based Prioritisation of COPD Interventions: A Narrative Review. (PubMed, Int J Chron Obstruct Pulmon Dis) - "Triple inhaled therapy showed context-dependent economic value across healthcare settings, while long-term azithromycin and long-term oxygen therapy combined with home mechanical ventilation were economically favourable primarily in selected high-risk populations. Ensifentrine and mepolizumab in type 2 COPD demonstrated clinically meaningful benefits but less favourable economic value at the prices evaluated in their source settings. ICS-containing therapy in low-eosinophil, non-exacerbating patients, household air pollution control, and comorbidity-directed interventions could not be formally classified because applicable COPD-specific economic evidence was insufficient. Integrating burden-reduction potential with ICER-based cost-effectiveness provides a conceptual framework for prioritising COPD interventions by health impact and economic value, while highlighting priorities for COPD-specific economic evaluation and future validation."

HEOR • Journal • Review • Chronic Obstructive Pulmonary Disease • Immunology • Infectious Disease • Influenza • Pneumococcal Infections • Pulmonary Disease • Respiratory Diseases • Tobacco Cessation

Phase 3 study results for ensifentrine (ENHANCE clinical trials). (ERS 2026) - "Sponsored by (Merck) MSD"

Clinical • P3 data • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Dual PDE3/4 inhibition with ensifentrine enhances triple therapy–mediated suppression of TNFα-induced inflammation in asthmatic airway cells (ERS 2026) - "However, no additional effect was observed on IL-6 secretion. These findings support further investigation of ensifentrine as an adjunct to triple therapy in patients with uncontrolled asthma, particularly in inflammatory pathways involving IL-8."

Asthma • Immunology • Inflammation • Respiratory Diseases • CXCL8 • IL6 • TNFA

Efficacy and Safety of Ensifentrine in Chinese Patients with Chronic Obstructive Pulmonary Disease: The ENHANCE-CHINA Randomized Clinical Trial (ERS 2026) - "Ensifentrine significantly improved lung function, symptoms, and quality of life in a Chinese COPD population."

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

Low concentrations of ensifentrine show superior anti-inflammatory activity to roflumilast in COPD airways (ERS 2026) - "No significant effects were detected in airway epithelium. Detailed results are shown in Figure 1.ConclusionsAt low, clinically relevant concentrations, the anti-inflammatory profile of ensifentrine in COPD airways is superior to that of roflumilast, supporting its potential to reduce exacerbations via inhalation."

Chronic Obstructive Pulmonary Disease • Immunology • Respiratory Diseases • CXCL8 • IL1B • IL33 • IL6 • TGFB1 • TNFA • TSLP

The effect of ensifentrine on disease stability in patients with COPD: a post-hoc pooled analysis of the ENHANCE trials (ERS 2026) - "Treatment with ensifentrine produced early and sustained disease stability in patients with moderate-to-severe COPD, according to several definitions of non-worsening."

Retrospective data • Chronic Obstructive Pulmonary Disease • Immunology • Respiratory Diseases

Effect of Dual Phosphodiesterase 3 and 4 Inhibitor Ensifentrine on Exacerbation Rate and Risk in Patients With Moderate to Severe COPD (CHEST 2026) - No abstract available

Clinical • Chronic Obstructive Pulmonary Disease • Immunology • Respiratory Diseases

REAL-WORLD EFFECTIVENESS OF ADJUNCTIVE ENSIFENTRINE IN COPD PATIENTS RECEIVING INHALED TRIPLE THERAPY: A PROPENSITY-MATCHED US COHORT STUDY (CHEST 2026) - No abstract available

Clinical • Real-world • Real-world effectiveness • Real-world evidence • Chronic Obstructive Pulmonary Disease • Immunology • Respiratory Diseases

A Phase IIb Ensifentrine-glycopyrrolate Fixed-dose Combination Dose Ranging Study in Subjects With COPD (clinicaltrials.gov) - P2 | N=497 | Completed | Sponsor: Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA | Active, not recruiting ➔ Completed | N=1119 ➔ 497

Enrollment change • Monotherapy • Trial completion • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

A Breath of Life Beyond Bronchodilation: Early Data on Hemodynamic and Functional Outcomes With Ensifentrine Nebulization in Severe COPD-associated Pulmonary Hypertension. (PubMed, Open Respir Med J) - "• The combination of ensifentrine with roflumilast was well tolerated. In this retrospective study, ensifentrine was safe and was associated with modest improvements in pulmonary hemodynamics and functional status in patients with severe COPD with pre-capillary PH. These preliminary findings warrant confirmation in larger, prospective, controlled trials."

Journal • Cardiovascular • Chronic Obstructive Pulmonary Disease • Hypertension • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Lung Function and Safety Outcomes in Patients With Moderate-to-Severe COPD Treated With Ensifentrine: A Pooled Analysis of the ENHANCE Trials. (PubMed, CHEST Pulm) - P3 | "Ensifentrine was well tolerated, with adverse event rates similar to placebo. Ensifentrine demonstrated early, sustained, and clinically significant improvements in lung function in a broad population and across all subgroups of patients with symptomatic moderate-to-severe COPD."

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

Bronchorelaxant and anti-inflammatory profile of ensifentrine alone and combined with inhaled medications in lipopolysaccharide-challenged human airways from chronic obstructive pulmonary disease donors. (PubMed, J Pharmacol Exp Ther) - "The effects of ensifentrine on bronchial relaxation were evaluated in response to carbachol and electrical field stimulation (EFS), also in combination with long-acting muscarinic antagonist (LAMA), long-acting β2-adrenoceptor agonists (LABA), and inhaled corticosteroids (ICS). It exhibits synergistic interactions with existing inhaler therapies, enhancing their efficacy. By demonstrating anti-inflammatory efficacy comparable to the established PDE4 inhibitor, roflumilast, our findings emphasize ensifentrine's capacity to significantly improve treatment outcomes and guide the development of optimized future combination strategies for COPD management."

Journal • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Oncology • Pulmonary Disease • Respiratory Diseases • IL10 • TNFA

Low-dose ensifentrine exerts anti-inflammatory effects comparable to roflumilast in COPD airways. (PubMed, Am J Respir Cell Mol Biol) - No abstract available

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

A Phase IIb Ensifentrine-glycopyrrolate Fixed-dose Combination Dose Ranging Study in Subjects With COPD (clinicaltrials.gov) - P2 | N=1119 | Active, not recruiting | Sponsor: Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA | Recruiting ➔ Active, not recruiting | N=480 ➔ 1119

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

The discovery and development of ensifentrine: A novel inhaled dual PDE3/4 inhibitor having 'bifunctional' bronchodilator and anti-inflammatory activity. (PubMed, Br J Pharmacol) - "Following extensive preclinical and clinical investigations, ensifentrine was recently approved by the FDA as a treatment for patients with chronic obstructive pulmonary disease (COPD). It is anticipated that this novel drug will provide a useful addition to the available treatments for pulmonary diseases."

Journal • Review • Asthma • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases

From Inflammation to Precision Medicine: Mechanistic Insights into Asthma, COPD, and IPF. (PubMed, Biomedicines) - "Advances include biologics such as dupilumab and benralizumab in eosinophilic COPD, and novel inhaled therapies such as ensifentrine, the first dual PDE3/4 inhibitor delivered via inhalation...Approved antifibrotics (nintedanib, pirfenidone) slow lung function decline, while new strategies target TGF-β, CTGF, and fibroblast-directed pathways. Across these diseases, biomarkers and the treatable traits framework are reshaping precision care. Personalized approaches integrating biomarkers, omics, and targeted therapies represent the most promising path for improved outcomes."

Journal • Review • Asthma • Chronic Obstructive Pulmonary Disease • Eosinophilia • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • Tobacco Cessation • CD8 • CTGF • IL13 • IL33 • IL4 • IL5 • TGFB1 • TSLP

Natural PDE4 inhibitors from plants: A comprehensive review of discovery, structure-activity relationships, and clinical translation potential. (PubMed, Eur J Med Chem) - "Although four PDE4 inhibitors have received FDA approval (roflumilast, apremilast, crisaborole, and ensifentrine), all suffer dose-limiting gastrointestinal side effects due to insufficient PDE4B/PDE4D selectivity. Despite promising potencies, critical gaps persist in subtype selectivity profiling, pharmacokinetic characterization, and metabolic stability. We propose that integrating AI-guided optimization, structure-informed isoform-selective design, nanodelivery systems, and biotechnology-enhanced production can accelerate clinical translation of these scaffolds."

Journal • Review • Asthma • Chronic Obstructive Pulmonary Disease • Dermatology • Immunology • Inflammation • Psoriasis • Pulmonary Disease • Respiratory Diseases

A Phase II Study of Ensifentrine in Non-Cystic Fibrosis Bronchiectasis (clinicaltrials.gov) - P2 | N=284 | Recruiting | Sponsor: Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA | N=180 ➔ 284 | Trial completion date: Sep 2026 ➔ Sep 2027 | Trial primary completion date: Sep 2026 ➔ Sep 2027

Enrollment change • Trial completion date • Trial primary completion date • Bronchiectasis • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

Nuance Pharma Announces Publication of Phase 3 ENHANCE-CHINA Data in the CHEST Journal (PRNewswire) - "The publication reports results from Nuance's successful ENHANCE-CHINA trial demonstrating improvements with ensifentrine in lung function and dyspnea, with a demonstrated safety profile....These data reinforce the robust clinical profile of ensifentrine, demonstrating meaningful improvements in lung function."

P3 data • Chronic Obstructive Pulmonary Disease • Immunology

A Phase IIb Ensifentrine-glycopyrrolate Fixed-dose Combination Dose Ranging Study in Subjects With COPD (clinicaltrials.gov) - P2 | N=480 | Recruiting | Sponsor: Verona Pharma plc | Trial completion date: Apr 2026 ➔ Jul 2026 | Trial primary completion date: Apr 2026 ➔ Jul 2026

Monotherapy • Trial completion date • Trial primary completion date • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases

Efficacy and Safety of Ensifentrine in Chinese Patients with Chronic Obstructive Pulmonary Disease: The ENHANCE-CHINA Randomized Clinical Trial. (PubMed, Chest) - "Ensifentrine significantly improved lung function and showed efficacy benefits in symptoms, quality of life improvement, and exacerbation reduction in Chinese individuals with COPD."

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

Summary of Research: Ensifentrine, a Novel Phosphodiesterase 3 and 4 Inhibitor for the Treatment of Chronic Obstructive Pulmonary Disease: Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase III Trials (the ENHANCE Trials). (PubMed, Adv Ther) - "It also reduced the rate and risk of flare-ups (called exacerbations) and was well tolerated. These results support the use of ensifentrine as an effective and well-tolerated treatment for people with COPD."

Clinical • Journal • P3 data • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases