New phase 3 ENHANCE-2 data support a potential submission by Verona Pharma to the FDA.
A promising dual pathway inhibitor molecule for the treatment of chronic obstructive pulmonary disease (COPD) has reached significant marks in phase 3 data and will now be considered by the US Food and Drug Administration (FDA).
Verona Pharma announced trial results from its pivotal phase 3 ENHANCE-2 study showing that novel inhaled ensifentrine nebulizer therapy was associated with a significant and clinically meaningful improvement in forced expiratory volume over 1 second (FEV1) among patients with COPD versus placebo.
With non-peer reviewed, unpublished findings announced Tuesday, Veron shared intention to submit a New Drug Application (NDA) for ensifentrine as a COPD treatment in early 2023—dependent on outcomes from the coinciding ENHANCE-1 study.
Ensifentrine is an investigational dual inhibitor of phosphodiesterase 3 and 4 (PDE3; PDE4)—a pair of enzymes associated with COPD bronchial and inflammatory effect. The agent was shown in prior phase 2 trials to significantly improve patient lung function and quality-of-life outcomes when used as either a monotherapy or add-on to maintenance bronchodilator in patients with COPD.
The ENHANCE-2 trial is part of a phase 3 randomized, double-blind, placebo-controlled program to assess the efficacy and safety of ensifentrine as either a monotherapy or add-on to long-acting muscarinic antagnonist (LAMA) or long-acting beta agonist (LABA) bronchodilators, versus placebo.
The patient population for ENHANCE-1 and ENHANCE-2 included approximately 800 patients with moderate to severe symptomatic COPD across North America and Europe. Patients in ENHANCE-2 were randomized to either 3 mg nebulized ensifentrine or placebo twice daily over 24 weeks.
Investigators sought a primary endpoint of lung function improvement per FEV1 area under the curve (AUC) at 0-12 hours post-dose in week 12. They additionally sought safety outcomes over 24 weeks, and secondary efficacy endpoints including peak and morning trough FEV1, COPD symptoms and health-related quality of life via St. George’s Respiratory Questionnaire (SGRQ) and Evaluating Respiratory Symptoms (E-RS) scores, and exacerbations.
Patients treated with ensifentrine reported a 94 mL change in mean FEV1 AUC 0-12 hours post-dose at week 12 (P <.0001). Investigators additionally observed significant improvements for treated subgroups based on sociodemographic and clinical backgrounds, including age, smoking status, disease severity and more.
Mean peak FEV1 of treated patients reached 146 mL at 0-4 hours post-dose in week 12 (P <.0001), and increase in morning trough FEV1 was 49 mL at week 12 (P = .0017). Investigators noted the latter secondary endpoint confirms a twice-daily dosing regimen for ensifentrine treatment in COPD.
Additionally, patients treated with ensifentrine reported a 42% reduction in COPD exacerbations over 24 weeks versus placebo (P = .0109), as well as clinically-important differences in E-RS and SGRQ scores at week 24.
Ensifentrine was observed to have good tolerability in ENHANCE-2, with a similar safety profile to placebo. Commonly observed adverse events included pneumonia, gastrointestinal effects and cardiovascular events.
In a statement accompanying the findings, Verona president and chief executive officer David Zaccardelli, Pharma, said the successful ENHANCE-2 findings and the ENHANCE-1 findings anticipated for later this year are expected to support the company’s NDA submission to the FDA.
“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,” Zaccardelli said.
Investigator Antonio Anzueto, MD, professor of medicine and chief of the pulmonary section at South Texas Veterans Healthcare System, highlighted the discernible improvements to lung function and retained safety associated with ensifentrine.
“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 therapym,” he said. “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.”