WASHINGTON -- Treatment with the first-in-class dual phosphodiesterase 3/4 inhibitor ensifentrine reduced exacerbation rates and improved other key outcomes in patients with chronic obstructive pulmonary disease (COPD), according to a pooled analysis of the phase III ENHANCE trials.
Compared with placebo, nebulized ensifentrine 3 mg met the primary endpoint of a statistically significant and clinically meaningful improvement in lung function in both trials.
At week 12, change in the forced expiratory volume in 1 second (FEV1) area under the curve 0 to 12 hours after dosing was 87 mL in ENHANCE-1 and 94 mL in ENHANCE-2 (P<0.0001 for both), reported Antonio Anzueto, MD, of the South Texas Veterans Healthcare System in San Antonio, during the American Thoracic Society annual meeting.
Over 24 weeks, treatment with ensifentrine also reduced the rate of moderate to severe COPD exacerbations by 36% in ENHANCE-1 and by 43% in ENHANCE-2, and reduced the risk of moderate-to-severe exacerbations, with a 38% risk reduction in ENHANCE-1 and a 42% risk reduction in ENHANCE-2.
Over 48 weeks, ensifentrine reduced exacerbation rate and risk compared with placebo in ENHANCE-1, with a rate reduction of 44% and a risk reduction of 52%.
Significant and consistent improvements in the Transition Dyspnea Index were also observed in both trials with ensifentrine, along with consistent decreases in daily mean rescue medication use.
These improvements were reported across all subgroups, with no significant differences related to sex, age, smoking status, COPD severity, background medication, chronic bronchitis, and FEV1 reversibility.
Previous findings showed that treatment with ensifentrine used as monotherapy or an add-on to maintenance bronchodilator therapy improved lung function and quality-of-life outcomes compared with placebo, Anzueto said.
The ENHANCE trials were designed to evaluate the clinical effects of ensifentrine 3 mg given twice a day via standard jet nebulizer versus placebo in patients with moderate-to-severe COPD who were mostly on background long-acting beta-agonists, long-acting muscarinic antagonists, inhaled corticosteroids, or a combination of the drugs.
Patients were excluded from the trials if they had asthma or a history of life-threatening COPD; if they were hospitalized for COPD, pneumonia, or COVID-19 in the previous 12 months; if they had COPD exacerbations requiring oral or IV steroids in the 3 months prior to randomization; or if they required pulmonary rehabilitation or long-term oxygen therapy.
ENHANCE-1 included 477 patients in the ensifentrine group and 283 in the placebo group. Mean age was 65, roughly 58% were men, and 56% were current smokers. About 68% of patients in both groups were taking background medication.
ENHANCE-2 included 498 patients in the ensifentrine group and 291 in the placebo group. Mean age was 65, roughly 48% were men, and 55% were current smokers. In this trial, 55% in both groups were taking background medication.
A spokesperson for drug developer Verona Pharma told Ƶ that the company is in the process of submitting a new drug application to the FDA for ensifentrine and plans to ask for priority review for the novel therapy.
"We believe there is a strong indication for priority review, but, of course, the FDA will make that call," the spokesperson said.
In addition to the oral presentation, data from ENHANCE-1 and ENHANCE-2 were presented in a dozen posters at the meeting, Anzueto said, adding that the findings will likely be published in a peer-reviewed journal within the next few months.
Disclosures
The ENHANCE studies were funded by Verona Pharma.
Anzueto reported consulting and/or serving on advisory boards for Verona Pharma, Boehringer Ingelheim, GSK, Novartis, Pfizer, AstraZeneca, and Teva Pharma.
Several co-authors reported being employed by and/or holding stock in Verona Pharma.
Primary Source
American Thoracic Society
Anzueto A, et al "Effect of ensifentrine, a novel PDE3 and PDE4 inhibitor, on lung function, symptoms and exacerbations in patients with COPD: the ENHANCE trials" ATS 2023.