Date: 2013-10-25
Type of information:
phase:
Announcement: publication of an article in The Lancet "Efficacy and safety of RPL554, a dual PDE3 and PDE4 inhibitor, in healthy volunteers and in patients with asthma or chronic obstructive pulmonary disease: findings from four clinical trials"
Company: Verona Pharma (UK)
Product: RPL554
Action mechanism: RPL554 is a long acting bronchodilator/anti-inflammatory drug belonging to a class of drugs known as a mixed phosphodiesterase (PDE) 3/4 inhibitor. Verona Pharma is investigating its use for the treatment of respiratory diseases including asthma, chronic obstructive pulmonary disease (COPD) and allergic rhinitis (hay fever).
Disease: chronic obstructive pulmonary disease (COPD)
Therapeutic area: Respiratory diseases
Country: UK
Trial details: The study is a randomized, double-blind, placebo-controlled study that will enroll 24 subjects. This trial is designed to test the anti-inflammatory properties of RPL554 in healthy subjects with respect to chronic obstructive pulmonary disease. The subjects will be treated once daily for 6 consecutive days with inhaled RPL554 before being challenged on the last day by an irritant agent that provokes an inflammatory response in their airways. The ability of RPL554 to reduce the amount of inflammation in the airways will be measured. This particular test resembles certain aspects of the airway inflammation in patients with COPD and is a common step in the development of new medicines for this disease. The study is expected to finish around year-end.
Latest
news: * On October 25, 2013, Verona Pharma has announced that a new research paper entitled “Efficacy and safety of RPL554, a dual PDE3 and PDE4 inhibitor, in healthy volunteers and in patients with asthma or chronic obstructive pulmonary disease: findings from four clinical trials” is now available on-line in The Lancet Respiratory Medicine.1 The peer-reviewed paper highlights the potential of Verona Pharma’s RPL554, to reverse the narrowing and reduce the inflammation of airways quicker and with fewer side effects compared to current treatments. In summary, the results from four proof-of-concept clinical trials with RPL554 showed that this novel dual PDE 3/4 inhibitor was well tolerated by healthy subjects, allergic asthmatics and patients with chronic obstructive pulmonary disease (COPD). The drug showed a rapid and sustained bronchodilator activity at least as effective as the benchmark therapy salbutamol across a range of doses, along with a highly significant anti-inflammatory activity. These studies demonstrate the importance of PDE3 in regulating airways tone in healthy and diseased airways and the role of PDE4, possibly together with PDE3, in regulating airways inflammation. Verona Pharma is initially pursuing development of the drug in a nebulized format suitable for the treatment of severe COPD patients, a significant unmet medical need with few novel approaches in clinical development. RPL554 is also suitable for incorporation into dry powder inhaler (DPI) and pressurised metered dose inhaler (pMDI) devices, likely to be part of long-term development plans for the agent.
* On April 29, 2013, Verona Pharma has announced the formation of a Clinical and Scientific Advisory Board (CSAB) of key opinion leaders in the fields of chronic obstructive pulmonary disease and asthma. The objective of the Advisory Board will be to help guide and inform the future clinical development of RPL554, a dual PDE3/4 inhibitor, which has so far successfully completed early Phase II clinical studies in COPD and asthma. Following a strategic review last year, the Company intends to initially concentrate further development of RPL554, in a nebulized form, as a treatment for severe COPD, a significant unmet medical need. Verona Pharma believes this could potentially shorten the time to commercialisation of the drug and so accelerate shareholder value creation.
The members of the Clinical and Scientific Advisory Board are: Prof. Mario Cazzola, Professor of Respiratory Medicine and Director of the Postgraduate School of Respiratory Medicine at the University of Rome „Tor Vergata?, Rome, Italy, where he is also Chief of the Respiratory Clinical Pharmacology Unit.
Prof. Paul O´Byrne, E. J. Moran Campbell Professor of Medicine and Chair of the Department of Medicine, McMaster University Canada. Also Executive Director of The Firestone Institute for Respiratory Health, Hamilton, Ontario, Canada.
Prof. Klaus Rabe, Professor of Pulmonary Medicine at the University of Kiel, Germany and Director of the Department of Pneumology at Clinic Grosshansdorf.
* On March 5, 2013, Verona Pharma has announced the results of an exploratory, placebo-controlled, double-blind clinical trial designed to specifically evaluate the anti-inflammatory properties of RPL554 in healthy subjects challenged with an inhaled irritant. This exploratory study showed a statistically significant reduction of total cells as well as in various types of inflammatory cells entering the airways in RPL554 treated, compared to placebo treated, subjects. The primary end point chosen for this exploratory trial was a reduction in the proportion of neutrophil cells, an inflammatory cell type recognised for its central role in COPD and severe asthma, to total inflammatory cells in the sputum and secondary endpoints included reductions in total inflammatory cell numbers. While there was a strong trend in favour of the primary endpoint, the study narrowly missed reaching statistical significance even though there was a highly significant reduction in the absolute number of neutrophils. Importantly, there were also statistically highly significant reductions in various types of inflammatory cells entering the airways in RPL554 treated subjects, providing positive evidence of the drug’s anti-inflammatory effects.
The study also showed that the drug was well tolerated with adverse events being mild and not significantly different to placebo. Consistent with earlier clinical studies with RPL554, there was no evidence of cardiovascular or gastrointestinal side effects.
Verona Pharma is currently developing RPL554, in a nebulised form, as a novel bronchodilator to treat patients with severe COPD, a significant unmet medical need. Previous clinical trials conducted by the Company have demonstrated that RPL554 is a potent bronchodilator with fast onset of action in both COPD and asthma patients. Near- to mid-term clinical development will focus on its bronchodilator properties in more severe patients. The Board believes that this focussed development will accelerate shareholder value growth. It is intended that the drug’s anti-inflammatory activity will be explored more fully in later studies to examine further the drug’s potential as a dual bronchodilator and anti-inflammatory treatment for patients with respiratory disease.
* On July 9, 2012, Verona Pharma has announced that it has began a new trial with its lead drug candidate, the dual PDE 3 and 4 inhibitor, RPL554. This clinical trial is taking place at the Medicines Evaluation Unit (MEU) in Manchester, UK and is designed to test the anti-inflammatory properties of RPL554 in healthy subjects with respect to chronic obstructive pulmonary disease.
