Verona Pharma is advancing its lead drug candidate, ensifentrine, through late-stage clinical trials for chronic obstructive pulmonary disease (COPD) and exploring its potential in treating COVID-19. The company recently announced positive results from the ENHANCE-2 phase 3 trial in COPD and is initiating a pilot study to assess ensifentrine's efficacy in hospitalized COVID-19 patients.
Ensifentrine Reduces COPD Exacerbations in Phase 3 Trial
The ENHANCE-2 trial, a phase 3 study evaluating ensifentrine as a chronic maintenance therapy for COPD, met its primary endpoint and demonstrated a significant reduction in moderate to severe exacerbations. The trial, which involved 789 patients, showed a 42% reduction in the rate of COPD exacerbations over 24 weeks with twice-daily nebulized ensifentrine. Furthermore, ensifentrine achieved significant improvements in lung function, as measured by forced expiratory volume in one second (FEV1) at 12 weeks, and in COPD symptom scores. Safety results were reported as similar to placebo. Notably, over half (52%) of the patients were receiving background therapy, including long-acting muscarinic antagonists (LAMA) or long-acting beta agonists (LABA), and 15% were on LAMA/LABA therapies combined with inhaled corticosteroids (ICS).
FDA Backs Phase 3 COPD Program
Verona Pharma has received positive feedback from the FDA regarding its end-of-phase 2 data package for ensifentrine in COPD. This paves the way for the initiation of two phase 3 trials, ENHANCE-1 and ENHANCE-2, later this year. The trials will evaluate nebulized ensifentrine 3mg twice daily as monotherapy and as an add-on to standard of care treatment in approximately 800 moderate to severe COPD patients. The primary endpoint will be improvement in lung function, measured by FEV1 over 12 hours, after 12 weeks of treatment. Secondary endpoints include peak and trough FEV1 and COPD symptoms.
Ensifentrine Investigated for COVID-19 Treatment
Beyond COPD, Verona Pharma is exploring the potential of ensifentrine in treating respiratory symptoms associated with viral infections, such as SARS-CoV-2. A pilot study is underway at the University of Alabama at Birmingham to assess the efficacy and safety of inhaled ensifentrine in hospitalized COVID-19 patients. The randomized, double-blind study will involve approximately 45 patients who will receive either 2mg of ensifentrine via pressurized metered-dose inhaler (pMDI) or placebo twice daily for up to 29 days. The primary endpoint is the proportion of patients recovered from COVID-19 and no longer hospitalized at day 29. Secondary endpoints include safety, tolerability, improvements in clinical status, time to recovery, supplemental oxygen use, and the proportion of patients needing mechanical ventilation and mortality.
Mechanism of Action and Potential Benefits
Ensifentrine is a first-in-class dual inhibitor of phosphodiesterase 3 and 4 (PDE3 and PDE4), combining bronchodilator and anti-inflammatory activities in a single compound. Clinical data from studies in other respiratory diseases suggest that ensifentrine improves oxygenation, reduces lung inflammation, and enhances mucus clearance. The drug has been well-tolerated in clinical trials involving over 1,300 people to date.
Mike Wells, a pulmonologist and principal investigator at the University of Alabama in Birmingham, noted, "Ensifentrine has demonstrated impressive effects on improving lung function and symptoms in patients with obstructive lung diseases, along with notable anti-inflammatory effects following inhaled dosing in clinical trials to date. Combined with positive safety results, ensifentrine has the potential to significantly benefit patients suffering from COVID-19."
