Publication details results from two studies demonstrating that RPL554 combined with standard short- and long-acting 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.”
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
* Singh D et al; Eur Respir J.2018 Aug 30. pii: 1801074. https://doi.org/10.1183/13993003.01074-2018
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
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2 Adeloye D, Chua S, et al. Global and regional estimates of COPD prevalence: Systematic review and meta–analysis.
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
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
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;
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