Verona Pharma Announces Ensifentrine Meets Primary Endpoint in Phase 3 ENHANCE-2 Trial for COPD

Statistically significant improvements in key measures of lung function

42% reduction in rate of exacerbations over 24 weeks

Well tolerated with safety results similar to placebo

Conference call today at 8:30 a.m. EDT / 1:30 p.m. BST

LONDON and RALEIGH, N.C., Aug. 09, 2022 (GLOBE NEWSWIRE) -- Verona Pharma plc (Nasdaq: VRNA) (“Verona Pharma” or the “Company”), today announces its top-line Phase 3 ENHANCE-2 (“Ensifentrine as a Novel inHAled Nebulized COPD thErapy”) trial results evaluating nebulized ensifentrine for the maintenance treatment of chronic obstructive pulmonary disease (“COPD”). The ENHANCE-2 trial has successfully met its primary endpoint, as well as secondary endpoints demonstrating improvements in lung function, and significantly reduced the rate and risk of COPD exacerbations.

Ensifentrine is a first-in-class, dual inhibitor of the enzymes phosphodiesterase 3 and 4 (“PDE3” and “PDE4”) combining bronchodilator and anti-inflammatory activities in one compound.

Highlights

• Study population (n=789):
  • Subject demographics and disease characteristics were well balanced between treatment groups.
  • Approximately 52% of subjects received background COPD therapy, either a long-acting muscarinic antagonist (“LAMA”) or a long-acting beta-agonist (“LABA”). Additionally, approximately 15% 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 average FEV₁ area under the curve 0-12 hours post dose at week 12 was 94 mL (p<0.0001) for ensifentrine.
  • Statistically significant and clinically meaningful improvements with ensifentrine demonstrated across all subgroups including gender, age, smoking status, COPD severity, background medication, ICS use, chronic bronchitis, FEV₁ reversibility, and geographic region.
• Secondary endpoints of lung function met:
  • Placebo corrected, increase in peak FEV₁ of 146 mL (p<0.0001) 0-4 hours post dose at week 12.
  • Placebo corrected, increase in morning trough FEV₁ of 49 mL (p=0.0017) at week 12, confirming twice daily dosing regimen.
• Exacerbation rate reduced:
  • Subjects receiving ensifentrine demonstrated a 42% reduction in the rate of moderate to severe COPD exacerbations over 24 weeks compared to those receiving placebo (p=0.0109).
  • Treatment with ensifentrine significantly decreased the risk of a moderate/severe exacerbation as measured by time to first exacerbation when compared with placebo by 42% (p=0.0088).
• COPD symptoms and Quality of Life (“QOL”):
  • Daily symptoms and QOL as measured by E-RS** Total Score and SGRQ** Total Score in the ensifentrine group improved from baseline to greater than the minimal clinically important difference (“MCID”) of -2 units and -4 units, respectively, at week 24. Improvements in these measures were seen as early as 6 weeks and showed continued improvement at 12 and 24 weeks, numerically exceeding placebo at each measurement. Statistical significance was not achieved due to improvements observed in the placebo group over time.
• Favorable safety profile:
  • Ensifentrine was well tolerated with safety results similar to placebo, including occurrence of pneumonia, gastrointestinal and cardiovascular adverse events.

^{*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: “Ensifentrine has demonstrated clear improvements in lung function in addition to favorable safety results. I am extremely excited by the clinically meaningful 42% reduction in the rate of exacerbations observed over 24 weeks in these symptomatic patients, many receiving background therapy. Based on these meaningful results, I believe ensifentrine, if approved, will be an important new class of bronchodilator and non-steroidal anti-inflammatory therapy for COPD patients providing a much needed alternative to existing treatments.”

David Zaccardelli, Pharm. D., Verona Pharma’s President and Chief Executive Officer, said: “We are very pleased by the successful outcome of our ENHANCE-2 study and remain committed to bringing ensifentrine to COPD patients as quickly as possible. These data, along with results from our ongoing Phase 3 trial, ENHANCE-1, which is on track to be reported around the end of 2022, if similarly positive, are expected to support the submission of a New Drug Application to the US Food and Drug Administration in the first half of 2023. We want to thank all the patients and investigators for their participation in the trial to advance ensifentrine as a potential new therapy for the treatment of COPD.”

Verona Pharma plans to release additional information from ENHANCE-2 at upcoming scientific conferences.

Conference Call and Webcast Information

Verona Pharma will host an investment community conference call at 8:30 a.m. EDT / 1:30 p.m. BST on Tuesday, August 9, 2022, to discuss the ENHANCE-2 results.

Analysts and investors may participate by dialing one of the following numbers and reference conference ID 2165062:

• Link to ENHANCE-2 call
• +1-888-317-6003 for callers in the United States
• +1-412-317-6061 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-2 results press release will also be made available today on the Company’s website.

About Ensifentrine

Ensifentrine (RPL554) is an investigational, first-in-class, dual inhibitor of the enzymes phosphodiesterase 3 and 4 (“PDE3” and “PDE4”) 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-2 clinical trial, 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 more than 2,200 subjects to date.

About the ENHANCE program

The two randomized, double-blind, placebo-controlled studies (ENHANCE-1 and ENHANCE-2) evaluate 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 up to approximately 20% of subjects may receive ICS. The two study designs replicate measurements of efficacy and safety data over 24 weeks and ENHANCE-1 also evaluates longer-term safety over 48 weeks.

• Patient Population: 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.
  

ENHANCE-1 completed enrollment in the 48-week subset in December 2021 and in the 24-week subset in June 2022. Further information about the ensifentrine Phase 3 program can be found at www.clinicaltrials.gov, NCT04535986 (ENHANCE-1) and NCT04542057 (ENHANCE-2).

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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. Ensifentrine met the primary endpoint in ENHANCE-2 demonstrating a statistically significant and clinically meaningful improvement in lung function. In addition, ensifentrine significantly reduced the rate of COPD exacerbations in the ENHANCE-2 trial. Two additional formulations of ensifentrine are in Phase 2 development for the treatment of COPD: dry powder inhaler (“DPI”) and pressurized metered-dose inhaler (“pMDI”). Ensifentrine also has potential applications in cystic fibrosis, asthma and other respiratory diseases. For more information, please visit www.veronapharma.com.

COVID-19 Impact

Verona Pharma continues to monitor the potential impact of the COVID-19 pandemic on its operations and clinical trials, in particular the timelines and costs of its Phase 3 ENHANCE clinical program. The pandemic and government and other measures in response continue to impact a number of clinical trial activities and the Company will provide an update if it becomes aware of any meaningful disruption caused by the pandemic to its clinical trials.

To help protect the health and safety of the subjects, caregivers and healthcare professionals involved in its clinical trials, as well as its employees and independent contractors, the Company continues to follow guidance from the FDA and other health regulatory authorities regarding the conduct of clinical trials during the COVID-19 pandemic to ensure the safety of study participants, minimize risks to study integrity, and maintain compliance with good clinical practice.

The COVID-19 pandemic is disrupting supply chains, and employee retention and recruitment, globally and the Company is closely monitoring this situation and will provide an update if it becomes aware of any meaningful disruption caused by the pandemic to the supply of ensifentrine and drug-related products, equipment and services for its clinical trials.

Russia-Ukraine Conflict

Verona Pharma is conducting ENHANCE-1 at a number of clinical trial sites in Russia and Europe (but not including Ukraine). The sanctions and other restrictions imposed by the U.S. and other countries as a result of the current conflict between Russia and Ukraine are impacting, and may continue to impact, the Company’s outsourced clinical research vendor’s ability to pay the clinical trial sites and investigators in Russia and may impact the vendor’s ability to supply ensifentrine and equipment to the sites and validate their trial data. If the conflict extends into other countries in Europe where the Company’s clinical trials are being conducted, its clinical trial activities in those countries may also be impacted. The Company is closely monitoring the Russia-Ukraine conflict and will provide an update if it becomes aware of any meaningful disruption to the cost and timelines of our Phase 3 program or its plans to submit an NDA for ensifentrine.

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 the progress and timing of clinical trials and data, the goals and design of clinical trials, the assumptions underlying the Company’s models on clinical trial enrollment and progress, including the potential impact of the COVID-19 pandemic on such progress and on our business and operations and the Company’s future financial results, planned regulatory submissions and timing thereof, 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, and the potential of ensifentrine in the treatment of COPD, cystic fibrosis, asthma and other respiratory diseases, as well as the potential of the DPI and pMDI formulations of ensifentrine.

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, 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, 2021and 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.