PDE3 and PDE4 are two enzymes implicated in the development and progression of immunological respiratory diseases, particularly rhinitis (hay fever) and asthma. RPL554 is a long-acting inhibitor of both these enzymes, and this action makes it a potential treatment for respiratory disease. As a PDE3 inhibitor, the drug is expected to result in bronchodilator actions, whilst the PDE4 component is expected to be anti-inflammatory.
RPL554 has successfully completed a number of pre-clinical studies.
RPL554 has been administered in more than 730 subjects in 12 clinical trials. In early-stage 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.
In March 2018, Verona reported positive top-line data from a double-blind, placebo-controlled, parallel group, phase 2b multi centre European study in the maintenance treatment of COPD. RPL554 produced 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. 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.
In March 2018, Verona reported positive top-line data from a phase 2a clinical trial evaluating the PK and PD profile, the tolerability of RPL554 in CF patients, with single doses achieving statistically significant (P<0.05) increases in average forced expiratory volume in one second (FEV1).