Verona Pharma Announces Ensifentrine Meets Primary and Key Secondary Endpoints in Phase 3 ENHANCE-1 Trial for COPD

Statistically significant improvements in lung function, symptoms and quality of life

36% reduction in rate of exacerbations over 24 weeks

Well tolerated safety profile over 48 weeks

NDA submission planned for 1H 2023

Conference call today at 8:30 a.m. EST / 1:30 p.m. GMT

LONDON and RALEIGH, N.C., Dec. 20, 2022 (GLOBE NEWSWIRE) -- Verona Pharma plc (Nasdaq: VRNA) (“Verona Pharma” or the “Company”), today announces positive results of its Phase 3 ENHANCE-1 trial evaluating nebulized ensifentrine for the maintenance treatment of chronic obstructive pulmonary disease (“COPD”). The ENHANCE-1 trial successfully met its primary and key secondary endpoints demonstrating significant improvements in lung function, symptoms and quality of life measures. In addition, ensifentrine substantially reduced the rate and risk of COPD exacerbations. Ensifentrine was well tolerated over 24 and 48 weeks.

Ensifentrine is a first-in-class, selective dual inhibitor of the enzymes phosphodiesterase 3 and 4 combining bronchodilator and non-steroidal anti-inflammatory activities in one compound.

Highlights

• Study population (n=763):
  • Subject demographics and disease characteristics were well balanced between treatment groups.
  • Approximately 66% of subjects received background COPD therapy, either a long-acting muscarinic antagonist (“LAMA”) or a long-acting beta-agonist (“LABA”). Additionally, approximately 21% of all subjects received inhaled corticosteroids (“ICS”) with concomitant LAMA or LABA.
• Primary endpoint met (FEV₁* AUC 0-12 hr):
  • 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.
• Key secondary endpoints of lung function, symptoms and quality of life measures met:
  • 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.
• Exacerbation rate and risk reduced:
  • 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).
  • Pooled exacerbation data from ENHANCE-1 and ENHANCE-2, ensifentrine demonstrated a 40% reduction in the rate of moderate to severe COPD exacerbations over 24 weeks (p=0.0012) compared to those receiving placebo. Additionally, ensifentrine significantly decreased the risk of a moderate/severe exacerbation as measured by time to first exacerbation when compared with placebo by 41% (p=0.0008).
• Favorable safety profile:
  • Ensifentrine was well-tolerated with very few events occurring in more than 1% of subjects and greater than placebo over 24 and 48 weeks.
    

^{*FEV₁: Forced Expiratory Volume in one second, a standard measure of lung function
**E-RS, Evaluating Respiratory Symptoms, and SGRQ, St. George’s Respiratory Questionnaire, are validated patient reported outcome tools}

Antonio Anzueto, MD, Professor of Medicine and Section, Chief of Pulmonary at South Texas Veterans Healthcare System, commented: “These exciting results demonstrate ensifentrine’s potential to become a first-in-class bronchodilator and non-steroidal anti-inflammatory therapy for COPD. 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.”

David Zaccardelli, Pharm. D., Verona Pharma’s President and Chief Executive Officer, said: “We are very pleased by the successful outcome of our Phase 3 ENHANCE-1 study, bringing us another step closer to providing a much needed novel therapy for COPD patients. The totality of the ENHANCE data including improvements in lung function, symptoms, quality of life measures and reduction in exacerbations, coupled with the consistent, favorable safety profile, support our belief that ensifentrine will change the treatment paradigm for COPD. We plan to submit a New Drug Application to the US Food and Drug Administration in the first half of 2023. We would like to thank all the patients and investigators for their participation in the ENHANCE program and we look forward to keeping you updated on our progress.”

Verona Pharma plans to release additional information from the ENHANCE trials at upcoming scientific conferences.

Conference Call and Webcast Information

Verona Pharma will host an investment community conference call at 8:30 a.m. EST / 1:30 p.m. GMT on Tuesday, December 20, 2022, to discuss the ENHANCE-1 results.

To participate, please dial one of the following numbers and ask to be placed into the Verona Pharma call:

• Link to ENHANCE-1 call
• +1-866-652-5200 for callers in the United States
• +1-412-317-6060 for international callers
  

A live webcast will be available on the Events and Presentations link on the Investors page of the Company's website, www.veronapharma.com, and the audio replay will be available for 90 days. An electronic copy of the ENHANCE-1 results press release will also be made available today on the Company’s website.

About Ensifentrine

Ensifentrine (RPL554) is an investigational, first-in-class, selective dual inhibitor of the enzymes phosphodiesterase 3 and 4 that combines bronchodilator and anti-inflammatory activities in one compound. In Phase 2 clinical studies in COPD, ensifentrine has shown significant and clinically meaningful improvements in lung function, symptoms and quality of life as a monotherapy or added onto a maintenance bronchodilator. In the Phase 3 ENHANCE-1 and ENHANCE-2 clinical trials, ensifentrine showed significant and clinically meaningful improvements in lung function measures and reduced the rate of COPD exacerbations. Ensifentrine has been well tolerated in clinical trials involving approximately 3,000 subjects to date.

About the ENHANCE program

The two randomized, double-blind, placebo-controlled studies (ENHANCE-1 and ENHANCE-2) evaluated the efficacy and safety of nebulized ensifentrine as monotherapy and added onto a single bronchodilator, either a LAMA or a LABA, compared to placebo, and approximately 20% of subjects received ICS. The two study designs replicated measurements of efficacy and safety data over 24 weeks and ENHANCE-1 also evaluated longer-term safety over 48 weeks.

• Patient Population: Each trial included approximately 800 moderate to severe, symptomatic, COPD patients in both studies at sites primarily in North America and Europe.
• Dose/Duration: Subjects were randomized to receive a 3 mg nebulized dose of ensifentrine or nebulized placebo twice daily for 24 weeks in ENHANCE-2 and 24 or 48 weeks in ENHANCE-1.
• Primary Endpoint: Improvement in lung function with ensifentrine as measured by average FEV₁ AUC 0-12 hours post dose at week 12.
• Secondary Endpoints: Lung function endpoints including peak and morning trough FEV₁, COPD symptoms and health-related quality of life through 24 weeks via SGRQ and E-RS, and exacerbations at 24 weeks.
• Safety: Assessed over 24 weeks in both studies and over 48 weeks in approximately 400 patients in ENHANCE-1.
  

Further information about the ensifentrine Phase 3 program can be found at www.clinicaltrials.gov, NCT04535986 (ENHANCE-1) and NCT04542057 (ENHANCE-2).

For further information please contact:

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 has evaluated nebulized ensifentrine in its Phase 3 clinical program ENHANCE (“Ensifentrine as a Novel inHAled Nebulized COPD thErapy”) for COPD maintenance treatment. Ensifentrine met the primary endpoint in both ENHANCE-1 and ENHANCE-2 trials demonstrating statistically significant and clinically meaningful improvements in lung function. In addition, ensifentrine significantly reduced the rate of COPD exacerbations in ENHANCE-1 and ENHANCE-2. Two additional formulations of ensifentrine are in Phase 2 development for the treatment of COPD: dry powder inhaler and pressurized metered-dose inhaler. Ensifentrine also 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, statements regarding the development of ensifentrine and plans to release data from the ENHANCE trials at future scientific conferences, the goals and design of clinical trials, planned regulatory submissions and timing thereof, including the timing of submission of an NDA to the FDA for ensifentrine, the potential for ensifentrine to be the first therapy for the treatment of respiratory diseases to combine bronchodilator and anti-inflammatory effects in one compound, the potential impact of ensifentrine for COPD patients and the treatment of COPD, and the potential of ensifentrine in the treatment of 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 subjects, 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, third-party service providers and licensees; our inability to realize the anticipated benefits under licenses granted by us to third parties to develop and commercialize ensifentrine, 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; lawsuits related to patents covering ensifentrine and the potential for our patents to be found invalid or unenforceable; lawsuits related to our licensing of patents and know-how with third parties for the development and commercialization of ensifentrine; changes in our tax rates, unavailability of certain tax credits or reliefs or exposure to additional tax liabilities or assessments could affect our profitability, and audits by tax authorities could result in additional tax payments for prior periods; and our vulnerability to natural disasters, global economic factors, geo-political actions and unexpected events, including health epidemics or pandemics like the COVID-19 pandemic, and conflicts such as the Russia-Ukraine conflict, which has and may continue to adversely impact our business. These and other important factors under the caption “Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2021 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.