Primary endpoint met; RPL554 produced clinically and statistically significant improvements in lung function at all dose levels
Clinically relevant secondary endpoints were also met, including statistically significant, progressive improvements in COPD symptoms
RPL554 was well tolerated at all dose levels in this four week 400 patient study
Management to hold conference call and webcast today at 8 am EDT / 1 pm BST
LONDON, March 26, 2018 (GLOBE NEWSWIRE) -- Verona Pharma plc (AIM:VRP) (Nasdaq:VRNA) (“Verona Pharma” or “the Company”), a clinical-stage biopharmaceutical company focused on developing and commercializing innovative therapies for respiratory diseases, announces today positive top-line data from its Phase 2b study evaluating RPL554, a first-in-class, inhaled, dual inhibitor of the enzymes phosphodiesterase 3 and 4 with bronchodilator and anti-inflammatory properties, as a maintenance treatment for chronic obstructive pulmonary disease (COPD).
The study met its primary endpoint, with RPL554 producing a clinically and statistically significant improvement in peak forced expiratory volume in one second (FEV1) at four weeks in patients with moderate-to-severe COPD compared to placebo. Furthermore, the peak FEV1 was significantly improved at all time points over the four weeks of dosing. Secondary endpoints measuring 12 hour average FEV1, COPD symptoms and Quality of Life were also met and support the potential clinical benefits of RPL554 for the treatment of COPD.
The four-week, double-blind, placebo-controlled, parallel group, Phase 2b multicenter European study performed in the out-patient setting evaluated the efficacy, safety, and dose-response of nebulized RPL554 administered twice-daily as a maintenance treatment for COPD in 403 patients with moderate-to-severe COPD. There were four dosing arms of RPL554 (0.75 mg, 1.5 mg, 3.0 mg and 6.0 mg) in the study in addition to placebo and patients were required to withhold use of regular long-acting bronchodilator therapy for the duration of the study.
- RPL554 met the primary endpoint at all doses, showing a statistically significant difference vs. placebo (p<0.001) with absolute changes from baseline >200mL in peak FEV1 after 4 weeks of dosing. No minimum effective dose could be determined.
- This peak bronchodilator effect was observed at the first dose and was sustained over four weeks (p<0.001).
Secondary endpoints include:
- Statistically significant improvements in average FEV1 over 12 hours were observed at all doses after the first administration, and this effect was sustained over four weeks.
- This study did not demonstrate consistent improvements in trough FEV1.
- Recording of daily COPD symptoms, using E-RS (EXACT-PRO)1, demonstrated a significant improvement in total COPD symptoms (p<0.002), including improvements in breathlessness (p<0.02), chest symptoms (p<0.02), and cough and sputum (p<0.02).
- Strong trend of improvement in SGRQ-C2 of >2.5 units was observed in all dose groups after four weeks.
- Patients’ Global Impression of Change3 indicates that patients felt better on RPL554 compared to placebo (p<0.01).
- RPL554 was well tolerated at all doses with an adverse event profile similar to placebo.
Dave Singh, M.D., Professor of Clinical Pharmacology and Respiratory Medicine, Medicines Evaluation Unit, University of Manchester, a Lead Investigator in the study, commented, “The results from this relatively large and well-designed study are very encouraging and clinically meaningful. The large and sustained improvement in lung function and reduction in COPD symptoms, including reduction in breathlessness, are particularly noteworthy. When coupled with the drug’s unique mechanism of action, these data underline the potential for RPL554 as a new complementary treatment for patients with this progressive and debilitating disease, where there remains a high unmet medical need.’’
Verona Pharma’s CMO, Ken Newman, M.D. said, “I am delighted that we met the primary endpoint of peak FEV1, confirming the strong bronchodilator effect of RPL554 in COPD patients. The clinically meaningful improvement in daily reported COPD symptom scores in all sub-domains, that continued to improve over the four week treatment period, is particularly exciting and promising.’’
“These results are very encouraging and strongly support the progression of RPL554 into later stage development as an inhaled treatment for COPD patients”, said Jan-Anders Karlsson, PhD., CEO of Verona Pharma. “The future clinical development and the positioning of this novel treatment will be informed by these data as well as by the outcome of the clinical study as an add-on to established combination therapies planned to start this year, and our ongoing market research”.
In previous clinical trials, RPL554 has been observed to result in bronchodilator effects when used alone or as an add-on treatment to other COPD bronchodilators. It has shown clinically meaningful and statistically significant improvements in lung function when administered in addition to frequently used short- and long-acting bronchodilators, such as tiotropium (Spiriva®), compared with such bronchodilators administered as a single agent. In addition, RPL554 has shown anti-inflammatory effects in a standard challenge study with COPD-like inflammation in human subjects. In these studies, RPL554 has been well tolerated. RPL554 also has a favorable safety and tolerability profile, having been administered in more than 730 subjects in 12 clinical trials.
1 E-RS (EXACT-PRO) - a recognized patient-reported outcome measure for use in clinical studies of COPD.
2 SGRQ-C - St. George’s Respiratory Questionnaire designed to measure impact on overall health, daily life, and perceived well-being in patients with COPD.
3 Patients’ Global Impression of Change - a scale reflecting the patient’s belief about the efficacy of treatment.
Verona Pharma will host an investment community conference call today at 8:00 a.m. Eastern Daylight Time (1:00 p.m. British Summer Time) to discuss the positive top-line data from the Phase 2b clinical trial in COPD disclosed in this press release.
Analysts and investors may participate in the conference call by utilizing the conference ID: 13677941 and dialing the following numbers:
- 1-877-423-9813 or + 1-201-689-8573 for callers in the United States
- 0 800 756 3429 for callers in the United Kingdom
- 0 800 182 0040 for callers in Germany
Those interested in listening to the conference call live via the internet may do so by visiting the “Events and Presentations” page on the “Investors” section of Verona Pharma’s website at http://investors.veronapharma.com/events-and-presentations/events and clicking on the webcast link. Slides highlighting the top-line data will also be posted to the “Events and Presentations” page.
Chronic obstructive pulmonary disease (COPD) is a progressive and life-threatening respiratory disease for which there is no cure.1 The condition damages the airways and the lungs, leading to persistent breathlessness, impacting a person’s daily life and their ability to perform simple activities such as walking a short flight of stairs or carrying a suitcase.1 Although COPD is thought to be underdiagnosed, globally, around 384 million people suffer from the disease.2 This number, according to the World Health Organization (WHO), is likely to increase in coming years, with estimates that COPD will become the third leading cause of death worldwide by 2030.1, Current COPD therapies focus on reducing and controlling symptoms. Yet, despite the wide availability of these treatments, many patients continue to suffer acute periods of worsening symptoms known as exacerbations. These exacerbations often lead to emergency department visits or hospital admissions and are also associated with high mortality.4 In the United States alone, the 2010 total annual medical costs related to COPD were estimated to be $32 billion and are projected to rise to $49 billion in 2020.5
About Verona Pharma plc
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. Verona Pharma’s product candidate, RPL554, is a first-in-class, inhaled, dual inhibitor of the enzymes phosphodiesterase 3 and 4 that acts as both a bronchodilator and an anti-inflammatory agent in a single compound. In clinical trials, treatment with RPL554 has been observed to result in statistically significant improvements in lung function as compared to placebo, and has shown clinically meaningful and statistically significant improvements in lung function when administered in addition to frequently used short- and long-acting bronchodilators as compared to such bronchodilators administered as a single agent. Verona Pharma is developing RPL554 for the treatment of chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and potentially asthma.
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 value of the top-line results from the Phase 2b clinical trial, RPL554 as a new complementary treatment for patients with COPD, projected annual medical costs related to COPD, the results of the Phase 2b trial supporting later stage development of RPL554, the future clinical development and positioning of RPL554, and the treatment potential for RPL554.
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 RPL554, 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 RPL554, 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 RPL554, which could adversely affect our ability to develop or commercialize RPL554; potential delays in enrolling patients, which could adversely affect our research and development efforts; we may not be successful in developing RPL554 for multiple indications; our ability to obtain approval for and commercialize RPL554 in multiple major pharmaceutical markets; misconduct or other improper activities by our employees, consultants, principal investigators, and third-party service providers; material differences between our “top-line” data and final data; our reliance on third parties, including clinical investigators, manufacturers and suppliers, and the risks related to these parties’ ability to successfully develop and commercialize RPL554; and lawsuits related to patents covering RPL554 and the potential for our patents to be found invalid or unenforceable. These and other important factors under the caption “Risk Factors” in our Annual Report on Form 20-F filed with the Securities and Exchange Commission (“SEC”) on February 27, 2018 relating to our Registration Statement on Form F-1, 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.
THIS ANNOUNCEMENT CONTAINS INSIDE INFORMATION FOR THE PURPOSES OF ARTICLE 7 OF REGULATION (EU) NO 596/2014.
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1 World Health Organization. Chronic Obstructive Pulmonary Disease. http://www.who.int/mediacentre/factsheets/fs315/en/. Accessed September 2017.
2 Adeloye D, Chua S, et al. Global and regional estimates of COPD prevalence: Systematic review and meta–analysis. J Glob Health 2015; 5(2): 020415.
3 World Health Organization. Burden of COPD. http://www.who.int/respiratory/copd/burden/en/. Accessed September 2017.
4 COPD Foundations. Characteristics of COPD Patients Using United States Emergency Care or Hospitalization. https://journal.copdfoundation.org/jcopdf/id/1103/Characteristics-of-COPD-Patients-Using-United-States-Emergency-Care-or-Hospitalization. Accessed September 2017.
5 Center for Disease Control. Increase Expected in Medical Costs for COPD. https://www.cdc.gov/features/ds-copd-costs/. Accessed September 2017.