Verona Pharma Completes Enrollment in Phase 2 Clinical Trial

Verona Pharma plc recently announced it has enrolled the last patient in its Phase 2 clinical trial evaluating the effect of nebulized RPL554 as an add-on to dual therapy using long-acting anti-muscarinic/long-acting beta2-agonists (LAMA/LABA) and triple therapy (LAMA/LABA with an inhaled corticosteroid) in the maintenance treatment of patients with moderate to severe chronic obstructive pulmonary disease (COPD). A total of 79 patients with COPD have enrolled at sites in the U.S. and in the UK in this three way crossover study. It is anticipated that it will take several weeks to complete dosing. Following data analysis, top line data is expected to be available in January 2019.

This randomized, double-blind, three-way crossover trial is designed 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 are delighted that enrollment in this Phase 2 study has been completed ahead of schedule and now expect to report top line data in January following completion of dosing and data analysis,” said Jan-Anders Karlsson, PhD, CEO of Verona Pharma, “We have already demonstrated that RPL554, when administered as an add-on to a single bronchodilator, produces a large and sustained improvement in lung function. This study is expected to further inform the positioning of RPL554 as an add-on to dual bronchodilator therapy (with some patients also on inhaled corticosteroid as background treatment) for the treatment of more severe COPD patients, who continue to experience disease progression and worsening of symptoms despite being treated with currently available COPD therapies.”

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).

COPD is a progressive and life-threatening respiratory disease for which there is no cure. Although COPD is thought to be underdiagnosed, globally, around 384 million people suffer from the disease. 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. 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. 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. 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. 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. There is an urgent need for drugs with novel mechanisms of action that can be used by these patients in addition to current therapies.

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 COPD, CF, and potentially asthma. For more information, visit www.veronapharma.com.