Verona Pharma Reports Positive Phase 2 Results with pMDI Formulation of Ensifentrine in COPD

Verona Pharma Reports Positive Phase 2 Results with pMDI Formulation of Ensifentrine in COPD

Primary and secondary lung function endpoints met

Results support twice-daily dosing

LONDON and RALEIGH, N.C., Feb. 02, 2021 (GLOBE NEWSWIRE) -- 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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About Ensifentrine

Ensifentrine (RPL554) is an investigational, first-in-class, inhaled, dual inhibitor of the enzymes phosphodiesterase 3 and 4 (“PDE3” and “PDE4”). This dual inhibition enables it to combine both bronchodilator and anti-inflammatory effects in one compound. Ensifentrine also activates the Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”), which is beneficial in reducing mucous viscosity and improving mucociliary clearance. Ensifentrine’s mechanism of action has the potential to alleviate respiratory symptoms such as breathlessness and cough and work against inflammation associated with COPD or inflammation triggered by viruses.

Ensifentrine has demonstrated significant and clinically meaningful improvements in both lung function and symptoms, including breathlessness, in Verona Pharma’s Phase 2 clinical studies in patients with moderate to severe Chronic Obstructive Pulmonary Disease (“COPD”). In addition, nebulized ensifentrine showed further improved lung function and reduced lung volumes in COPD patients taking standard short- and long-acting bronchodilator therapy, including maximum bronchodilator treatment with dual/triple therapy. Ensifentrine has been well tolerated in clinical trials involving more than 1,300 subjects to date.

About Verona Pharma

Verona Pharma is a clinical-stage biopharmaceutical company focused on developing and commercializing innovative therapies for the treatment of respiratory diseases with significant unmet medical needs. If successfully developed and approved, Verona Pharma’s product candidate, ensifentrine, has the potential to be the first therapy for the treatment of respiratory diseases that combines bronchodilator and anti-inflammatory activities in one compound. The Company is evaluating nebulized ensifentrine in its Phase 3 clinical program ENHANCE (“Ensifentrine as a Novel inHAled Nebulized COPD thErapy”) for COPD maintenance treatment. The Company raised gross proceeds of $200 million through a private placement in July 2020 and expects the funds to support its operations and Phase 3 clinical program into 2023. Two additional formulations of ensifentrine are currently in Phase 2 development for the treatment of COPD: dry powder inhaler (“DPI”) and pressurized metered-dose inhaler (“pMDI”). Ensifentrine is being evaluated in a pilot clinical study in patients hospitalized with COVID-19 and has potential applications in cystic fibrosis, asthma and other respiratory diseases. For more information, please visit www.veronapharma.com.

Forward-Looking Statements

This press release contains forward-looking statements. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including, but not limited to, the development of ensifentrine and the progress and timing of clinical trials and data, the goals and design of clinical trials, the potential for ensifentrine to be a first-in-class phosphodiesterase 3 and 4 inhibitor and to be the first therapy for the treatment of respiratory diseases to combine bronchodilator and anti-inflammatory effects in one compound, the broad utility of ensifentrine delivered via nebulizers and handheld inhalers, the potential of ensifentrine to significantly benefit patients with COVID-19 and to be safe and well tolerated in those patients, the potential of ensifentrine to alleviate respiratory symptoms such as breathlessness and cough and work against inflammation triggered by viruses, the sufficiency of funds to supports its operations and Phase 3 clinical program into 2023, and the potential of ensifentrine in the treatment of COPD, cystic fibrosis, asthma and other respiratory diseases.

These forward-looking statements are based on management's current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from our expectations expressed or implied by the forward-looking statements, including, but not limited to, the following: our limited operating history; our need for additional funding to complete development and commercialization of ensifentrine, which may not be available and which may force us to delay, reduce or eliminate our development or commercialization efforts; the reliance of our business on the success of ensifentrine, our only product candidate under development; economic, political, regulatory and other risks involved with international operations; the lengthy and expensive process of clinical drug development, which has an uncertain outcome; serious adverse, undesirable or unacceptable side effects associated with ensifentrine, which could adversely affect our ability to develop or commercialize ensifentrine; potential delays in enrolling patients, which could adversely affect our research and development efforts and the completion of our clinical trials; we may not be successful in developing ensifentrine for multiple indications; our ability to obtain approval for and commercialize ensifentrine in multiple major pharmaceutical markets; misconduct or other improper activities by our employees, consultants, principal investigators, and third-party service providers; our future growth and ability to compete depends on retaining our key personnel and recruiting additional qualified personnel; material differences between our “top-line” data and final data; our reliance on third parties, including clinical research organizations, clinical investigators, manufacturers and suppliers, and the risks related to these parties’ ability to successfully develop and commercialize ensifentrine; and lawsuits related to patents covering ensifentrine and the potential for our patents to be found invalid or unenforceable; and our vulnerability to natural disasters, global economic factors and other unexpected events, including health epidemics or pandemics like the novel coronavirus (COVID-19). These and other important factors under the caption “Risk Factors” in our Registration Statement on Form F-1 filed with the SEC on August 17, 2020, our Report on Form 6-K filed with the SEC on November 24, 2020, and our other reports filed with the SEC, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management's estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release.