Verona Pharma Reports Positive Top-Line Data from Phase 2b Clinical Trial of RPL554 for Maintenance Treatment of COPD
March 26, 2018 |
LONDON, UK – March 26, 2018 – Verona Pharma plc, 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), 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-C of >2.5 units was observed in all dose groups after four weeks.
- Patients’ Global Impression of Change 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.
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.