Verona Pharma initiates Phase 2 study of RPL554

Clinical-stage biopharmaceutical company Verona Pharma announced the initiation of a Phase 2 clinical trial to evaluate the pharmacokinetic (PK) profile, efficacy and safety of a dry powder inhaler (DPI) formulation of ‘RPL554’, in patients with moderate to severe chronic obstructive pulmonary disease (COPD), on Monday.

The AIM-traded firm described RPL554 as a first-in-class, inhaled, dual inhibitor of the enzymes phosphodiesterase 3 and 4, designed to have bronchodilator as well as anti-inflammatory properties, which was currently in development for the maintenance treatment of COPD, cystic fibrosis (CF) and asthma.

It said the randomised, double-blind, placebo-controlled, two-part study with the DPI formulation, being conducted at one site in the US, would enrol around 36 patients with COPD.

The primary objective of the first part of the study was to evaluate the PK profile following a single dose of RPL554, when administered by DPI.

Secondary objectives included evaluating the safety, tolerability and the bronchodilator effect of a single dose of RPL554 administered by DPI.

The second part of the study, conducted as a multiple dose crossover study, would evaluate the bronchodilator effect of repeat doses of RPL554 administered by DPI in terms of “peak forced expiratory volume in one second” (FEV1).

Secondary objectives of that part of the study included evaluating the safety, tolerability and bronchodilator effect of repeat doses of RPL554 administered by DPI, as well as the PK profile, onset of action, and the amount of rescue medication use during treatment periods.

Data from the single dose part of the study were expected during the first half of 2019.

RPL554 had been studied via the nebulised route of administration in 12 completed clinical trials involving more than 730 subjects.

Verona Pharma said it demonstrated in previous Phase 2 trials in patients with COPD that nebulized RPL554 “significantly improved” lung function, including improved peak FEV1, reduced lung hyperinflation, and faster onset-of-action, when added to some of the most commonly used COPD treatments, including tiotropium, ipratropium, and albuterol.

The studies also reportedly showed that RPL554 was well tolerated.

“Positive results using inhaler formulations could dramatically expand the clinical utility and commercial opportunity for RPL554 in the maintenance treatment of COPD and potentially broaden its use for other respiratory indications, such as asthma,” said Verona Pharma chief executive officer Jan-Anders Karlsson.

“With an estimated 5.4 million people using inhalers for the maintenance treatment of COPD in the US alone, and another one million patients using nebulised formulations, we believe it is important to understand how RPL554 works via these different delivery platforms in order to fully realize and leverage its clinical potential for patients with respiratory diseases.

“We look forward to building upon the positive results that have been garnered to date utilising the nebulised formulation of RPL554.”

In addition, Verona Pharma said it was currently conducting a Phase 2 clinical trial to evaluate nebulised RPL554 as an add-on treatment to dual LAMA/LABA therapy and triple LAMA/LABA/ICS therapy, and also planned to evaluate RPL554 as a metered-dose inhaler (MDI) formulation as part of a comprehensive clinical program to fully demonstrate the clinical utility of RPL554 in improving the standard of care for COPD.