Verona Pharma Announces Analyses Demonstrating Ensifentrine Reduced Exacerbation Rates Across Subgroups in Phase 3 ENHANCE-2 Trial for COPD

LONDON and RALEIGH, N.C., Oct. 14, 2022 (GLOBE NEWSWIRE) -- Verona Pharma plc (Nasdaq: VRNA) (“Verona Pharma” or the “Company”), announces additional exacerbation* subgroup analyses from the Phase 3 ENHANCE-2 (“Ensifentrine as a Novel inHAled Nebulized COPD thErapy”) trial in chronic obstructive pulmonary disease (“COPD”). Top-line results from the trial are available on Verona Pharma’s website here.

As previously reported, in the overall study population, ensifentrine demonstrated a 42% reduction in the rate of moderate to severe exacerbations over 24 weeks compared to those receiving placebo (p=0.0109). Results of the subgroup analyses confirmed positive effects consistent with the exacerbation reduction observed in the overall population across all subgroups analyzed over 24 weeks. ENHANCE-2 was not powered for exacerbation rate in subgroups.

Exacerbation rate reduction by subgroup

*An exacerbation was defined as a worsening of symptoms (two major or one major and one minor) requiring minimum of three days treatment with oral/systemic steroids and/or antibiotics or hospitalization

**Background medication included either a long-acting muscarinic antagonist (“LAMA”) or a long-acting beta-agonist (“LABA”). Approximately 15% of subjects also received inhaled corticosteroids (“ICS”)

“We are very encouraged by the meaningful and consistent reductions in rates of COPD exacerbations across all subgroups analyzed,” said David Zaccardelli, Pharm. D., President and Chief Executive Officer. “Despite treatment with available therapies, many COPD patients continue to experience exacerbations, which are estimated to cause approximately 1.9 million emergency department visits and 740,000 hospitalizations per year in the United States alone. Pending assessment of the results from our ongoing Phase 3 trial, ENHANCE-1, which is on track to read out around the end of 2022, these exacerbation data will be included in the New Drug Application in the US, which we expect to submit in the first half of 2023.”

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

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 subjects 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 subjects 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 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 the progress and timing of clinical trials and data, the goals and design of clinical trials, planned regulatory submissions and timing and content 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 and commercialization, 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 Securities and Exchange Commission, 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.