A phase 3 clinical trial revealed that treatment with nebulized ensifentrine led to significant improvements in lung function, symptoms and quality of life measures in COPD patients, according to manufacturer Verona Pharmaceuticals. Ensifentrine successfully met these primary and key secondary endpoints, and substantially reduced the rate and risk of COPD exacerbations, results from the phase 3 ENHANCE-1 trial showed.
Ensifentrine (RPL554) is an investigational, first-in-class, selective dual inhibitor of the enzymes phosphodiesterase 3 and 4 combining bronchodilator and non-steroidal anti-inflammatory activities in one compound.
Data from the Enhance-1 study of 763 patients included:
- Placebo corrected, change from baseline in FEV1 area under the curve 0-12 hours post dose at week 12 was 87 mL (p<0.0001) for ensifentrine.
- Demonstrated consistent improvements in all subgroups including gender, age, smoking status, COPD severity, background medication, ICS use, chronic bronchitis, FEV1 reversibility and geographic region.
- Placebo corrected, increase in peak FEV1 of 147 mL (p<0.0001) 0-4 hours post dose at week 12.
- Daily symptoms as measured by E-RS** Total Score in the ensifentrine group improved from baseline to greater than the minimal clinically important difference (“MCID”) of -2 units with a statistically significant improvement compared to placebo at week 24. Improvements in symptoms were early and sustained with statistical significance versus placebo at weeks 6, 12 and 24.
- Quality of Life (“QOL”) as measured by SGRQ** Total Score in the ensifentrine group improved from baseline to greater than the MCID of -4 units with a statistically significant improvement compared to placebo at week 24. Improvements in QOL were early and sustained with statistical significance versus placebo at weeks 6, 12 and 24.
- Placebo corrected, increase in morning trough FEV1 of 35 mL (p=0.0421) at week 12, supporting twice daily dosing regimen.
- Subjects receiving ensifentrine demonstrated a 36% reduction in the rate of moderate to severe COPD exacerbations over 24 weeks (p=0.0505) compared to those receiving placebo.
- Treatment with ensifentrine significantly decreased the risk of a moderate/severe exacerbation as measured by time to first exacerbation when compared with placebo by 38% (p=0.0378).
- Ensifentrine was well-tolerated with very few events occurring in more than 1% of subjects and greater than placebo over 24 and 48 weeks.
“These exciting results demonstrate ensifentrine’s potential to become a first-in-class bronchodilator and non-steroidal anti-inflammatory therapy for COPD,” said Antonio Anzueto, MD, Professor of Medicine and Section, Chief of Pulmonary at South Texas Veterans Healthcare System. “The 36% reduction in the rate of exacerbations observed over 24 weeks in symptomatic patients is impressive. Combined with the significant improvements in lung function, symptom and quality of life measures, as well as the favorable safety profile, these data confirm ensifentrine’s potential to change the treatment paradigm for COPD patients.”