Ensifentrine meets primary endpoint in phase III ENHANCE-2 trial for COPD

The ENHANCE-2 trial has successfully met its primary endpoint, as well as secondary endpoints demonstrating improvements in lung function, and significantly reduced the rate and risk of COPD exacerbations.Ensifentrine is a first-in-class, dual inhibitor of the enzymes phosphodiesterase 3 and 4 (“PDE3” and “PDE4”) combining bronchodilator and anti-inflammatory activities in one compound.

Highlights: Study population (n=789): Subject demographics and disease characteristics were well balanced between treatment groups. Approximately 52% of subjects received background COPD therapy, either a long-acting muscarinic antagonist (“LAMA”) or a long-acting beta-agonist (“LABA”). Additionally, approximately 15% of all subjects received inhaled corticosteroids (“ICS”) with concomitant LAMA or LABA.

Primary endpoint met (FEV1 AUC 0-12 hr): i. Placebo corrected, change from baseline in average FEV1 area under the curve 0-12 hours post dose at week 12 was 94 mL (p<0.0001) for ensifentrine. ii. statistically significant and clinically meaningful improvements with ensifentrine demonstrated across all subgroups including gender, age, smoking status, copd severity, background medication, ics use, chronic bronchitis, fev1 reversibility, and geographic region.

Secondary endpoints of lung function met: i.Placebo corrected, increase in peak FEV1 of 146 mL (p<0.0001) 0-4 hours post dose at week 12. ii. placebo corrected, increase in morning trough fev1 of 49 ml (p="0.0017)" at week 12, confirming twice daily dosing regimen.

Exacerbation rate reduced: i. Subjects receiving ensifentrine demonstrated a 42% reduction in the rate of moderate to severe COPD exacerbations over 24 weeks compared to those receiving placebo (p=0.0109). ii. Treatment with ensifentrine significantly decreased the risk of a moderate/severe exacerbation as measured by time to first exacerbation when compared with placebo by 42% (p=0.0088).

COPD symptoms and Quality of Life (“QOL”): i. Daily symptoms and QOL as measured by E-RS Total Score and SGRQ Total Score in the ensifentrine group improved from baseline to greater than the minimal clinically important difference (“MCID”) of -2 units and -4 units, respectively, at week 24. Improvements in these measures were seen as early as 6 weeks and showed continued improvement at 12 and 24 weeks, numerically exceeding placebo at each measurement. Statistical significance was not achieved due to improvements observed in the placebo group over time.

Favorable safety profile: Ensifentrine was well tolerated with safety results similar to placebo, including occurrence of pneumonia, gastrointestinal and cardiovascular adverse events.

FEV1: Forced Expiratory Volume in one second, a standard measure of lung function. E-RS, Evaluating Respiratory Symptoms, and SGRQ, St. George’s Respiratory Questionnaire, are validated patient reported outcome tools.

Antonio Anzueto, MD, Professor of Medicine and Section, Chief of Pulmonary at South Texas Veterans Healthcare System, commented: “Ensifentrine has demonstrated clear improvements in lung function in addition to favorable safety results. I am extremely excited by the clinically meaningful 42% reduction in the rate of exacerbations observed over 24 weeks in these symptomatic patients, many receiving background therapy. Based on these meaningful results, I believe ensifentrine, if approved, will be an important new class of bronchodilator and non-steroidal anti-inflammatory therapy for COPD patients providing a much needed alternative to existing treatments.”

David Zaccardelli, Pharm. D., Verona Pharma’s President and Chief Executive Officer, said: “We are very pleased by the successful outcome of our ENHANCE-2 study and remain committed to bringing ensifentrine to COPD patients as quickly as possible. These data, along with results from our ongoing Phase III trial, ENHANCE-1, which is on track to be reported around the end of 2022, if similarly positive, are expected to support the submission of a New Drug Application to the FDA in the first half of 2023. We want to thank all the patients and investigators for their participation in the trial to advance ensifentrine as a potential new therapy for the treatment of COPD.”

Verona Pharma plans to release additional information from ENHANCE-2 at upcoming scientific conferences.