Verona Pharma announced positive top-line results on the use of nebulized ensifentrine as an add-on to tiotropium (Spiriva Respimat) in people with moderate-to-severe chronic obstructive pulmonary disease (COPD).
The results come from a Phase 2b clinical trial (NCT03937479), which showed that ensifentrine — when added as a nebulized suspension to inhaled tiotropium — significantly improved the participants’ lung function and quality of life.
Ensifentrine, previously known as RPL554, acts as both a bronchodilator to widen the airways and as an anti-inflammatory agent. It works by inhibiting the phosphodiesterase 3 and 4 (PDE3 and PDE4) enzymes linked to COPD development.
The Phase 2b trial, launched in 2019, enrolled 416 people with moderate-to-severe COPD who received either placebo or nebulized ensifentrine as an add-on to tiotropium treatment. The treatment was given twice daily for four weeks. Those participants who received ensifentrine were given a dose of 0.375, 0.75, 1.5, or 3.0 mg.
The primary endpoint of the trial was an improvement in lung function, measured by the total amount of air forcefully exhaled in one second (forced expiratory volume in one second, or FEV1).
After four weeks of treatment with ensifentrine plus tiotropium, the researchers found that participants’ FEV1 significantly increased in proportion to the dose of ensifentrine they were taking. Those results suggest that the therapeutic combination resulted in a clinically and statistically significant, dose-dependent improvement in lung function.
The improvements in FEV1 ranged from 78 mL for the 0.375 mg dose, to 124 mL for the 3.0 mg dose.
Further, the positive effects on lung function were maintained for up to 12 hours, suggesting that taking ensifentrine twice per day is an effective dose regimen.
The secondary endpoint of the trial was an improvement in the patients’ health-related quality of life. The results showed that participants who took either 1.5 mg or 3.0 mg of ensifentrine — the two highest doses — had a significant and clinically meaningful improvement in their quality of life, compared with placebo.
Concerning safety, patients receiving ensifentrine tolerated well all four doses tested, and did not experience more adverse effects than those who received the placebo treatment.
These results are important for helping the researchers select the appropriate doses for a future Phase 3 clinical trial testing ensifentrine.
“We are delighted with these results in symptomatic COPD patients already on steady-state maintenance treatment with a long-acting LAMA bronchodilator. These data bring clarity to planning the design, including dose selection, endpoints and background therapy, of our Phase 3 program,” Jan-Anders Karlsson, PhD, CEO of Verona Pharma, said in a press release.
The company plans to launch Phase 3 trials in the third quarter of this year. Before that, it will have an End-of-Phase 2 meeting with the U.S. Food and Drug Administration to discuss the data obtained thus far.
“We are committed to demonstrating ensifentrine’s potential to produce sustained bronchodilation and anti-inflammatory effects in symptomatic COPD patients in Phase 3 trials, which we expect to start in 3Q 2020,” Karlsson said.
“The strong effect on both bronchodilation and quality of life as an add-on to tiotropium is impressive and consistent with prior studies with ensifentrine,” said Gary Ferguson, MD, pulmonary physician and principal investigator at the Pulmonary Research Institute of Southeast Michigan.
“I am particularly interested to see the significant improvements in quality of life measurements over the 4 week treatment period. This is very important for patients that remain symptomatic despite using standard COPD medications,” Ferguson said.
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