This three-way crossover study will inform design of pivotal Phase 3 trials
Top line data expected first quarter 2019
LONDON, UK I August 01, 2018 I Verona Pharma plc (AIM:VRP) (Nasdaq:VRNA) (“Verona Pharma”), a clinical-stage biopharmaceutical company focused on developing and commercializing innovative therapies for respiratory diseases, announces the initiation of a Phase 2 clinical trial evaluating the effect of nebulized RPL554 as an add-on to treatment with dual long-acting anti-muscarinic / long-acting beta2-agonist drugs (“LAMA/LABA”), which are commonly used in the maintenance treatment of patients with moderate to severe chronic obstructive pulmonary disease (“COPD”). The first patients have been enrolled and dosed in the study, and top line data are expected in the first quarter of 2019.
RPL554 is a first-in-class, inhaled, dual inhibitor of the enzymes phosphodiesterase 3 and 4 designed to have bronchodilator as well as anti-inflammatory properties, and is currently in development for the maintenance treatment of COPD and for the treatment of cystic fibrosis (“CF”).
The randomized, double-blind, three-way crossover trial, being conducted at sites in the U.S. and in the U.K., will enroll approximately 75 patients with COPD to investigate the efficacy and safety of nebulized RPL554 as an add-on to an inhaled LAMA/LABA, tiotropium/olodaterol (Stiolto® Respimat®), compared to placebo. Those patients already receiving inhaled corticosteroid (“ICS”) anti-inflammatory therapy will continue a stable dose of ICS throughout the study, thus providing additional data on “triple therapy” use. Following a 7- to 14-day washout period in advance of dosing and between study arms, patients will receive three days of treatment with each of two dose strengths (1.5 mg or 6.0 mg) of nebulized RPL554 or placebo twice daily. The primary endpoint of this trial is improvement in lung function with RPL554 vs placebo (as add-on to tiotropium/olodaterol), as measured by peak forced expired volume in one second (FEV1), a standard measure of exhaled breath volume to evaluate respiratory function.
“We have already demonstrated that RPL554 is an effective add-on treatment to short- and long-acting bronchodilators in COPD patients. This Phase 2 trial will now examine the effect of RPL554 as an add-on to LAMA/LABA therapy, and in some patients to triple therapy, as many of these COPD patients continue to experience breathing difficulties and daily symptoms that impair their quality of life despite concomitant treatment with two bronchodilators. We believe the bronchodilator and anti-inflammatory properties of RPL554 may be particularly useful in this large group of patients with high, unmet medical need. This phase 2 trial is intended to provide important data to inform the design of pivotal Phase 3 studies with RPL554, expected to commence later next year,” said Jan-Anders Karlsson, PhD, CEO of Verona Pharma.
About COPD
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.
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.
SOURCE: Verona Pharma
