29 September 2015, Cardiff – Verona Pharma plc (AIM: VRP.L), the drug development company focused on first-in-class medicines to treat respiratory diseases, today announces encouraging positive headline data of the third and final part (part C) of a randomised, double blind, placebo controlled Single Ascending Dose (SAD) / Multiple Ascending Dose (MAD) clinical study in stable chronic obstructive pulmonary disease (COPD) patients. This study uses a new proprietary and commercially scalable nebulised suspension formulation of the Company's lead pipeline drug, RPL554.1,2 The primary objective of this part of the study was to show the safety and tolerability of the new drug formulation in stable COPD patients with moderate severity of disease.3 Measurement of lung function using FEV14 was included. Evaluation of the full data set is ongoing and will be presented in an appropriate scientific, peer-reviewed forum at a later date.
Highlights: Part C of study in 32 stable COPD patients with moderate disease severity3
Primary objective of study met: Drug formulation well tolerated at all dose levels; No serious adverse events reported
- Adverse event profile similar to that seen with placebo
- Absence of gastro-intestinal or cardiovascular adverse events
RPL554 caused pronounced improvement in lung function
- Mean peak FEV1 increase ranged from 199ml to 257ml versus placebo
- Extent of bronchodilation exceeds that seen in earlier studies with original proof of concept formulation
- Data continue to support twice daily dosing regimen with RPL554
Data consistent with that from earlier part A and B of study in healthy volunteers
- Evaluation of the full data set from this trial is ongoing
In the third part of the trial, nebulised RPL554, a novel dual PDE3/PDE4 inhibitor, was administered twice daily using a new proprietary, commercially scalable, suspension formulation to stable COPD patients with moderate disease severity for up to five-and-a-half consecutive days at doses significantly in excess of the previously used active dose. Patients withheld their regular bronchodilator therapy for the duration of the treatment phase of the study.
The study met its primary objective and all doses of RPL554 were found to be well tolerated. As with earlier parts of the trial, which were conducted in healthy volunteers, there were no reports of serious adverse events and the adverse event profile was similar to that seen with placebo. In particular, there was an absence of gastro-intestinal or cardiovascular adverse events.
Lung function, as measured by peak FEV1, was increased in all dose groups and ranged between 199-257ml over placebo suggesting a clinically meaningful bronchodilator effect which will be confirmed in Phase IIb studies. In the highest dose there was a small increase in heart rate as might be expected from the pharmacology of the product.
The new commercially scalable formulation of RPL554 results in a uniform suspension of RPL554 and was designed to provide improved tolerability, allowing higher doses of RPL554 to be inhaled, yielding an optimised bronchodilator effect than with the previous prototype, solution formulation. Additionally the new formulation offers potential for improvements in convenience and compliance. Data to date supports this profile, suggesting a twice daily dosing regimen and is consistent with a longer residence time of the drug in lung tissue and slower release into the blood than with the original formulation. In addition, the commercial viability of the new formulation is underlined by significantly improved stability compared to the previous formulation.
Professor Dave Singh of the Medicines Evaluation Unit, University of Manchester, lead investigator on this study, commented: "I am very encouraged by the headline results of this study using the new suspension formulation of RPL554. The marked improvement in lung function seen in this initial small study shows that this product has potential to be a meaningful addition to existing treatment options for COPD."
Dr. Jan-Anders Karlsson, Chief Executive of Verona Pharma, said: "We are excited by the robust and consistent results arising from our SAD/MAD study of RPL554 in both healthy volunteers and now, stable COPD patients with moderate disease severity. The data demonstrates that, as designed, the new commercially scalable, suspension formulation is well tolerated and has allowed us to extend the dose range and the duration of bronchodilation effect that can be produced in COPD patients. We will now fully analyse the data from this trial. While we need to discuss these results and confirm our further development plans for the drug with the appropriate regulatory authorities, we currently expect to begin Phase IIb studies in the second half of 2016."
RPL554 is currently in development as a nebulised treatment for acute exacerbations in COPD patients in a hospital or home-care setting. The nebuliser bronchodilator market was worth about $1 billion in 2014 in the US.5 RPL554 also has potential as a novel drug for the maintenance therapy of COPD, for patients with asthma and cystic fibrosis.
Phase I and Phase II studies with RPL554 in the previous nebulised solution formulation were successfully conducted in over 100 subjects.6 Results collectively showed that the drug is a very potent bronchodilator with the ability to elicit a unique anti-inflammatory response. In these initial studies, patients treated with RPL554 had an adverse event profile which was similar to that in patients treated with placebo. The original nebulised formulation of the drug used in these studies was devised to provide proof-of-concept data, before the development of a new formulation suitable for commercial scale-up.