First Patient Dosed in Phase 2a Clinical Trial of Verona Pharma’s RPL554 for Cystic Fibrosis

Patrícia Silva, PhD avatar

by Patrícia Silva, PhD |

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The first patient has been dosed in a Phase 2 clinical trial evaluating RPL554 as a treatment for cystic fibrosis (CF), according to its maker, Verona Pharma.

RPL554 is a first-in-class drug candidate designed to inhibit the enzymes phosphodiesterase 3 and 4 (PDE3/PDE4). It has been shown to have anti-inflammatory and bronchodilatory properties. A bronchodilator increases air flow to the lungs.

The Phase 2a trial (NCT02919995) is recruiting up to 10 CF patients in the United Kingdom. It will  evaluate RPL554’s effect on lung function, plus its pharmacokinetics, pharmacodynamics and tolerability. Pharmacokinetics is the science of how an organism affects a drug, and pharmacodynamics how a drug affects an organism.

Previous studies showed that RPL554 stimulated the cystic fibrosis transmembrane conductance regulator, or CFTR. Mutations of the protein render ion channels in the protective epithelial cells of the lungs dysfunctional, leading to CF.

RPL554 also reduced phlegm in the airways, reduced airway obstruction, and inhibited inflammation, prior studies showed.

Another clinical trial showed that RPL554 improved lung function in patients with chronic obstructive pulmonary disease (COPD), compared with those who took a placebo. The same trial showed that RPL554 improved lung function when added to two bronchodilators.

In addition, RPL554 was found to have anti-inflammatory effects in a study of people with COPD-like inflammation.

“Cystic fibrosis is the most common fatal inherited disease in the United States and Europe. More than 30,000 people in the U.S. and more than 70,000 people worldwide are living with cystic fibrosis,” Jan-Anders Karlsson, PhD, chief executive officer of Verona, said in a press release.

“Two recently approved therapies are indicated only for a subset of CF patients, and there is a need for novel, effective anti-inflammatory medications to treat the underlying inflammation in cystic fibrosis. RPL554 has a differentiated mechanism of action, and pre-clinical data in cystic fibrosis combined with our positive clinical data in COPD, leads us to believe it has the potential to be an important new treatment for this debilitating condition. We look forward to progressing the drug through this study and expect to announce top-line data in the first half of 2018,” Karlsson added.

Verona Pharma received its second Venture and Innovation Award from the UK Cystic Fibrosis Trust in October of 2016 to fund the new trial. Its first award funded pre-clinical-trial studies of RPL554 for the treatment of CF in 2014.

“The Venture Innovation Awards are designed to ensure that the Trust’s funds go as far as possible to supporting ground-breaking treatments and innovative research by bringing in vital external funding. The RPL554 trial has the potential to make a difference to the lives of people with CF, and we are thrilled that the drug is moving into this important trial stage,” said Paula Sommer, head of research at the UK Cystic Fibrosis Trust.

The Phase 2a trial is being conducted at the Cambridge Center for Medical Research at Papworth Hospital in the United Kingdom. For more information about the trial and how to participate, please visit this link.