Verona Pharma plc (VRNA) Announces Positive Phase 2 Results with pMDI Formulation of Ensifentrine in COP

Verona Pharma plc (NASDAQ: VRNA) (“Verona Pharma”), a clinical-stage biopharmaceutical company focused on respiratory diseases, announces positive Phase 2 data with a pressurized metered-dose inhaler (“pMDI”) formulation of ensifentrine in patients with moderate to severe chronic obstructive pulmonary disease (“COPD”).

Ensifentrine delivered by pMDI met all of the primary and secondary lung function endpoints in the 7 day, Phase 2 clinical trial. The magnitude of improvement in lung function was dose-ordered and highly statistically significant at peak and over the 12-hour dosing interval compared with placebo, and supports twice-daily dosing of ensifentrine via pMDI for the treatment of COPD.

Highlights

• Primary endpoint met at all doses: highly statistically significant and clinically meaningful increase in lung function as measured by peak forced expiratory volume in one second (“FEV1”)1 measured over 4 hours post-dose, compared to placebo after 7 days of treatment. Improvements in peak FEV1 corrected for placebo were 205 mL (p<0.0001) for the 300 mg dose, 277 mL (p<0.0001) for the 1000 mg dose, and 326 mL (p<0.0001) for the 3000 mg dose.
• Secondary lung function endpoints met: results support twice-daily dosing.Statistically significant improvements in average FEV1 over 12 hours corrected for placebo (average FEV1 AUC (0-12hr)2) were 120 mL (p=0.0018) for the 300 mg dose, 187 mL (p<0.0001) for the 1000 mg dose, and 197 mL (p<0.0001) for the 3000 mg dose.Statistically significant improvements in morning trough FEV1 corrected for placebo were 46 mL (not significant) for the 300 mg dose, 80 mL (p=0.0115) for the 1000 mg dose, and 110 mL (p=0.0066) for the 3000 mg dose.Statistically significant improvements in average FEV1 over 4 hours corrected for placebo (average FEV1 AUC (0-4hr)2) were 178 mL (p<0.0001) for the 300 mg dose, 256 mL (p<0.0001) for the 1000 mg dose, and 301 mL (p<0.0001) for the 3000 mg dose.

• Ensifentrine pMDI formulation was well tolerated at each dose with an adverse event profile similar to placebo.

“Demonstrating this magnitude of improvement in lung function is exciting,” said Dave Singh, M.D., Professor of Clinical Pharmacology and Respiratory Medicine, Medicines Evaluation Unit, University of Manchester, and Investigator in the study. “Combined with ensifentrine’s unique dual mechanism of action and favorable efficacy and safety profile already demonstrated in multiple Phase 2 clinical trials via nebulizer and dry powder inhaler (“DPI”), these data strengthen its potential as a novel therapeutic for COPD.”

David Zaccardelli, Pharm. D., President and CEO of Verona Pharma, said: “We are very encouraged by these compelling data, which are consistent with results from Phase 2 clinical trials with our nebulized and DPI formulations of ensifentrine. All three inhaled formulations have demonstrated significant improvements in lung function in COPD patients, supporting the broad utility of ensifentrine delivered via nebulizers and handheld inhalers.

The development of pMDI and DPI formulations of ensifentrine provides expanded opportunities including life cycle management, new indications and partnering.”

Study Design

The randomized, double-blind, two-part Phase 2 trial evaluated the pharmacokinetics, efficacy and safety of pMDI ensifentrine for the treatment of moderate to severe COPD after a single dose and repeat doses over 7 days. Part A of the study evaluated the pharmacokinetic profile, safety and efficacy following a single dose of ensifentrine over 5 dose levels in a parallel group design. In Part B, patients who completed Part A were randomized to receive 3 doses of ensifentrine (300 mg, 1000 mg, or 3000 mg) or placebo twice-daily over 7 days in a complete block crossover design.

Single Dose Trial, Part A

• Patient Population: 40 moderate to severe COPD patients at two sites in the UK.
• Dose/Duration: Patients were randomized to receive a single dose out of five dose levels (100 µg, 300 µg, 1000 µg, 3000 µg, 6000 µg) of pMDI ensifentrine or placebo.

Multiple Dose Crossover Trial, Part B

• Patient Population: 28 moderate to severe COPD patients who participated in Part A continued to Part B at two sites in the UK.
• Dose/Duration: Patients were randomized to receive 3 dose levels (300 µg, 1000 µg, 3000 µg) of pMDI ensifentrine or placebo, twice-daily over 7 days. All patients were to receive each of the dose levels and placebo over four 7-day treatment periods.

Endpoints

• Primary Endpoint: Improvement in lung function as measured by peak FEV1 over 4 hours post-dose with ensifentrine compared to placebo after 7 days of treatment.
• Secondary Endpoints: Safety and tolerability, other lung function measures such as trough FEV1, average FEV1 over 4 and 12 hours, and steady state pharmacokinetic profile of ensifentrine pMDI.

Further information about this clinical trial can be found at ClinicalTrials.gov, NCT04091360.

1Peak FEV1: Peak Forced Expiratory Volume in one second, was measured as the highest FEV1 value recorded over 4 hours post-dose. FEV1 is a standard measure of lung function.2FEV1 AUC(0-12hr) and FEV1 AUC(0-4hr): Area Under the Curve 0-12 hours and 0-4 hours calculated using the trapezoidal rule, divided by the observation time (12 hours or 4 hours) to report in mL, a measure of the aggregate effect over 12 hours or 4 hours.

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