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Verona Pharma Announces Publication of Key Paper on RPL554 in COPD in the European Respiratory Journal
Publication demonstrates RPL554’s significant bronchodilation effect, in both large and small airways, alone and when combined with currently used bronchodilators in COPD patients
LONDON, Sept. 06, 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, today announced that the high-impact, peer reviewed European Respiratory Journal has published a paper entitled “The short term bronchodilator effects of the dual PDE3 and PDE4 inhibitor RPL554 in COPD” that provides full results from two positive Phase 2 clinical studies with RPL554.* Results from these studies were previously reported by Verona Pharma on May 10, 2016 and September 7, 2017. RPL554 is the Company’s lead first-in-class drug candidate that has a dual bronchodilator and anti-inflammatory mechanism of action. RPL554 has potential as an add-on therapy to improve lung function and reduce symptom severity in chronic obstructive pulmonary disease (COPD) patients whose disease is not being adequately managed by the current standard of care.
Publication details results from two studies demonstrating that RPL554 combined with standard short- and long-acting bronchodilators:
- Causes a pronounced additional bronchodilator effect in both large and small airways.
- Reduces lung hyperinflation, considered a cause of breathlessness in COPD patients.
- Improves speed of onset of action when combined with standard bronchodilators.
The first study detailed in the publication compared the short-term bronchodilator effects of nebulized RPL554 with that of the commonly used bronchodilators salbutamol (a short-acting beta-agonist) and ipratropium (a short-acting anti-muscarinic agent), as well as placebo, in patients with reversible COPD. Additional bronchodilator effects when adding RPL554 on top of these agents was also measured.
The second study detailed the extent of any additional bronchodilation that is achievable, in this patient group, when adding RPL554 to tiotropium (the long-acting anti-muscarinic Spiriva®, one of the most commonly used drugs to treat COPD). In both studies, peak forced expiratory volume in one second (FEV1) lung volumes and specific airway conductance (sGAW) were studied as the principle measures of airway function. In both studies RPL554 demonstrated a placebo like side-effect profile.
The statistically significant results from these studies clearly demonstrate that the bronchodilator effect of RPL554 in patients with reversible COPD is, at the very least, of similar magnitude as that of the commonly used bronchodilators studied, and that clinically meaningful additional bronchodilation could be achieved by adding RPL554 to the treatment of patients with such drugs. The paper concludes that “…RPL554 provided additional bronchodilation, reduced gas trapping, improved airway conductance, and a more rapid onset of action when administered in combination with either a beta-2 agonist or muscarinic antagonist. These short-term bronchodilator studies provide support to further study RPL554 in longer term COPD studies focused on other endpoints including symptoms and exacerbations.”
Jan-Anders Karlsson, PhD, CEO of Verona Pharma, said: “The statistically significant results from the two Phase 2 trials detailed in this important paper continue to highlight the potential and differentiated profile of RPL554 as an add-on therapy to improve lung function and reduce symptom severity in COPD patients whose disease is not being adequately managed by the current standard of care.”
Dave Singh, M.D., Professor of Clinical Pharmacology and Respiratory Medicine, Medicines Evaluation Unit, University of Manchester, and Principal Investigator in these studies, added: “The results published in the European Respiratory Journal not only profile the significant effect of RPL554 on improving lung function in COPD patients when used alone or in combination with commonly used bronchodilators, but also its rapid onset of action, especially when used in combination.”
Verona Pharma is currently conducting a Phase 2 clinical trial to evaluate RPL554 as an add-on treatment to dual LAMA/LABA therapy and triple LAMA/LABA/ICS therapy, as part of a comprehensive clinical program to fully demonstrate the clinical utility of RPL554 in improving the standard of care for COPD. These data will also support the planning of the RPL554 phase 3 program.
Paper Abstract in Full
Introduction: We investigated the short-term bronchodilator effects of RPL554 (an inhaled dual phosphodiesterase 3 and 4 inhibitor) combined with other bronchodilators in COPD patients with reversibility (>150 mL to short acting bronchodilators).
Methods: Study 1: six way placebo controlled crossover study (n=36) with single doses of RPL554 (6mg), salbutamol (200μg), ipratropium (40μg), RPL554 + salbutamol, RPL554 + ipratropium and placebo. Study 2: three way crossover study (n=30) of tiotropium (18 μg) combined with RPL554 (1.5 mg or 6mg) or placebo for 3 days. FEV1, lung volumes and sGaw were measured.
Results: Study 1; Peak FEV1 change compared to placebo was similar with RPL554, ipratropium and salbutamol (means 223, 199 and 187 mL respectively). The peak FEV1 was higher for RPL554 + ipratropium versus ipratropium (mean difference 94 mL, p<0.0001) and RPL554 + salbutamol versus salbutamol (mean difference 108 mL; p<0.0001). Study 2 (day 3); both RPL554 doses caused greater peak FEV1 effects than placebo. The average FEV1 (0- 12h) increase was greater with RPL554 6mg only versus placebo (mean difference 65 mL p=0.0009). In both studies, lung volumes and sGAW showed greater RPL554 combination treatment effects versus monotherapy.
Conclusion: RPL554 combined with standard bronchodilators caused additional bronchodilation and hyperinflation reduction.
Chronic obstructive pulmonary disease (“COPD”) is a progressive and life-threatening respiratory disease for which there is no cure.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 2030.1,3 The condition damages the airways and the lungs, leading to persistent symptoms of 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 Many experience acute periods of worsening symptoms called ‘exacerbations’, often leading 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 30-40% of moderate to severe COPD patients on triple inhaled therapy (ICS/LAMA/LABA) remain uncontrolled and continue to experience airway obstruction (breathing difficulties), COPD symptoms and exacerbations.6 There is an urgent need for drugs with novel mechanisms of action that can be used by these patients in addition to current therapies.
* Singh D et al; Eur Respir J. 2018 Aug 30. pii: 1801074. https://doi.org/10.1183/13993003.01074-2018
About Verona Pharma plc and RPL554
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 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. RPL554 improved FEV1 over four weeks in patients with moderate-to-severe COPD when compared to placebo and improved COPD symptoms and Quality of Life in a Phase 2b multicenter European study performed in 403 patients. In addition, RPL554 has shown anti-inflammatory effects in a standard challenge study with COPD-like inflammation in human subjects. RPL554 has been well tolerated in these studies and has a favorable safety and tolerability profile, having been administered to more than 730 subjects in 12 clinical trials. 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 design of the Phase 2 clinical trial of RPL554, the timing of availability of top-line data for the Phase 2 clinical trial, the importance of the Phase 2 clinical trial to our development plans for RPL554, the potential of RPL554 as a promising first-in-class treatment option for COPD, and the value of the data and insights that may be gathered from the Phase 2 clinical trial, including for the purpose of designing pivotal Phase 3 trials.
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 and the completion of our Phase 2 trial; we may not be successful in developing RPL554 for multiple indications; our ability to obtain regulatory approvals necessary to conduct later stage trials and to 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.
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1World 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 Health2015; 5(2): 020415.
3World 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.
5Center for Disease Control. Increase Expected in Medical Costs for COPD. https://www.cdc.gov/features/ds-copd-costs/. Accessed September 2017.
6 Mullerova H., et al., Characterization of COPD Patients Treated With Inhaled Triple Therapy Containing Inhaled Corticosteroid [ICS], Long-Acting Beta2-Agonists [LABA], and Long-Acting Muscarinic Antagonists [LAMA] in the UK, American Journal of Respiratory and Critical Care Medicine 2017;195:A4986
6 Vestbo J, et al., Single inhaler extrafine triple therapy versus long-acting muscarinic antagonist therapy for chronic obstructive pulmonary disease (TRINTY); a double-blind, parallel group, randomised controlled trial, The Lancet, Vol 389, p. 1919-1929; May 13, 2017.