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Verona’s Phase 2 study of nebulized ensifentrine without statistical significance for its primary endpoint

Verona Pharma’s testing nebulized ensifentrine  given twice daily in two doses, on top of inhaled Stiolto, Respimat, to treat COPD patients, misses primary endpoint of peak forced expiratory volume in one second, on day 3 of treatment.

In the announcement of the top-line data from its three-day Phase 2 trial, given twice daily in 1.5 mg and 6.0 mg, Verona said that, although primary endpoint was missed, the ensifentrine 1.5 mg morning dose improved peak FEV1 by 46 mL, compared to placebo.

Verona said that peak FEV1 after evening dose on day 3 showed statistically significant improvement, compared to placebo, with both doses, with ensifentrine 1.5 mg showing a 130 mL improvement and ensifentrine 6.0 mg showing an 81 mL improvement.

Another thing was reported, which has not shown to be statistically significant when adjusted for multiple doses, that is ensifentrine at a 1.5 mg dose produced consistent improvements, compared to placebo, in average FEV1 over 12 hours following the morning dose on days 1 to 3, with an improvement of approximately 50 mL on day 3.

Statistically significant reductions in mean residual volume were observed 15 minutes following the evening dose on day 3, with ensifentrine 1.5 mg showing a reduction of 259 mL (p<0.002) and ensifentrine 6.0 mg showing a reduction of 142 mL.
Ensifentrine was well tolerated at both doses with an adverse event profile consistent with that observed in prior studies, but 6.0 mg did not result in greater improvement in lung function as compared with the ensifentrine 1.5 mg dose.

However, Dave Singh, M.D., Professor of Clinical Pharmacology and Respiratory Medicine, Medicines Evaluation Unit, University of Manchester, said that achieving additional bronchodilator response of this magnitude in COPD patients that have previously been considered to be maximally bronchodilated on background dual or triple therapy in a short, three-day study is clinically meaningful and unprecedented.

He said: “The statistically significant reduction observed in residual volume for the ensifentrine 1.5 mg dose at certain time points, which is closely related to dyspnea or breathlessness, highlights the potential for ensifentrine to provide symptomatic improvement for patients with this progressive and debilitating disease. I look forward to seeing data from longer-term studies evaluating the bronchodilator and anti-inflammatory activity of this unique mechanism of action.”

Verona’s CEO, Jan-Anders Karlsson,  said: “Having demonstrated in previous studies the potential of ensifentrine to deliver benefits to patients on no or single bronchodilator therapy, we believe that this short study continues to support our view that ensifentrine may also be of benefit to more severe COPD patients on dual and triple therapy, for whom there are few other treatment options. While we are disappointed that this exploratory Phase 2 study did not achieve statistical significance for its primary endpoint, these data give us clarity on the design, including dose and background therapy, for future long-term studies. We now have the opportunity to also include patients on dual and triple therapy, with the goal of further evaluating ensifentrine’s potential to produce sustained bronchodilation and anti-inflammatory effect in this large number of symptomatic COPD patients.”

In Phase 2 clinical trials completed to date, ensifentrine has been observed to result in bronchodilator effects when used alone or as an add-on treatment to other COPD bronchodilators, and has also shown anti-inflammatory effects in a standard challenge study with COPD-like inflammation in human subjects. Verona Pharma is currently conducting a Phase 2 trial to evaluate a dry powder inhaler  formulation of ensifentrine for the maintenance treatment of COPD. The company also plans to evaluate ensifentrine in a metered-dose inhaler  formulation as part of a comprehensive clinical program intended to fully demonstrate the clinical utility of ensifentrine in improving the standard of care for COPD.

Study Design

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