Treatment with nebulized ensifentrine was associated with improvements in lung function, and significantly reduced the rate and risk of chronic obstructive pulmonary disease (COPD) exacerbations, according to topline results from a phase 3 trial.
Ensifentrine (RPL554) is a first-in-class, dual phosphodiesterase (PDE) 3 and 4 inhibitor with combined bronchodilator and anti-inflammatory actions. The randomized, double-blind, placebo-controlled ENHANCE-2 trial (ClinicalTrials.gov Identifier: NCT04542057) evaluated the efficacy and safety of nebulized ensifentrine as monotherapy or as an add-on to a long-acting muscarinic antagonist (LAMA) or a long-acting beta-agonist (LABA) in patients with moderate to severe COPD. Patients were randomly assigned to receive either nebulized ensifentrine 3mg twice a day or placebo for 24 weeks.
The primary endpoint was the change from baseline of average forced expiratory volume in 1 second (FEV1) area under the curve (AUC) 0 to 12 hours post dose at week 12. Secondary end points included peak and morning trough FEV1, COPD symptoms and health-related quality of life (St. George’s Respiratory Questionnaire) at 24 weeks.
Results showed that treatment with ensifentrine met the primary endpoint demonstrating a statistically significant and clinically meaningful improvement in lung function (change from baseline in average FEV1 area under the curve 0 to 12 hours post dose was 94mL [P <.0001]). Improvements in secondary endpoints were also observed with an increase in peak FEV1 of 146mL at 0 to 4 hours post dose (P <.0001) and an increase in morning trough FEV1 of 49mL (P =.0017).
Compared with placebo, patients treated with ensifentrine experienced a 42% reduction in the rate of moderate to severe COPD exacerbations (P =.0109). The investigational treatment also significantly reduced the risk of a moderate to severe exacerbation by 42% (P =.0088). While not statistically significant, there were improvements observed in COPD symptoms and quality of life in the ensifentrine treatment arm.
“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,” said David Zaccardelli, PharmD, Verona Pharma’s President and Chief Executive Officer. “These data, along with results from our ongoing phase 3 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 US Food and Drug Administration in the first half of 2023.”
According to the Company, additional data from the ENHANCE-2 trial will be presented at upcoming scientific conferences.
Verona Pharma announces ensifentrine meets primary endpoint in phase 3 ENHANCE-2 trial for COPD. News release. Verona Pharma plc. Accessed August 9, 2022. https://www.globenewswire.com/news-release/2022/08/09/2494468/0/en/Verona-Pharma-Announces-Ensifentrine-Meets-Primary-Endpoint-in-Phase-3-ENHANCE-2-Trial-for-COPD.html