First patient dosed in Verona cystic fibrosis treatment trial

Clinical-stage biopharmaceutical company focused on developing and commercialising innovative therapeutics for the treatment of respiratory diseases, Verona Pharma, announced on Tuesday that the first patient had been enrolled and dosed in a Phase 2a clinical study to evaluate its product candidate, RPL554, as a treatment for cystic fibrosis.

The AIM-traded firm said the Phase 2a single-dose trial was being conducted in the United Kingdom, and the primary objective of the double-blind, placebo-controlled study would evaluate the pharmacokinetic and pharmacodynamics profile and tolerability of RPL554 in up to 10 CF patients, as well as examine the effect on lung function.

It said it received its second Venture and Innovation Award from the UK Cystic Fibrosis Trust in October to fund the clinical trial.

Verona Pharma received its first Venture and Innovation Award to fund exploratory preclinical studies of RPL554 for the treatment of CF in 2014.

The trial was being performed at the Cambridge Centre for Medical Research at Papworth Hospital, Cambridge, which the board described as one of the largest specialist cardiothoracic hospitals in Europe, by lead investigator Professor Andres Floto.

RPL554 was described as a first-in-class, inhaled, dual inhibitor of the enzymes phosphodiesterase 3 and 4, with anti-inflammatory as well as bronchodilatory properties, currently in development for the treatment of chronic obstructive pulmonary disease and CF.

In preclinical studies, RPL554 was observed to stimulate the CF transmembrane conductance regulator, a protein whose mutation results in dysfunctional ion channels in epithelial cells, leading to CF.

Based on available data, RPL554 reportedly has the potential to enhance mucociliary clearance - that is, reduce phlegm in the airway - reduce airway obstruction and inhibit inflammation.

In previous clinical trials in patients with COPD, RPL554 had been observed to result in statistically significant improvements in lung function as compared to placebo and showed clinically meaningful and statistically significant improvements in lung function when added to two commonly used bronchodilators, compared to either bronchodilator administered as a single agent, Verona said.

RPL554 also showed anti-inflammatory effects in a standard challenge study with COPD-like inflammation in human subjects.

In those previous studies, RPL554 was said to be well-tolerated.

Cystic fibrosis is the most common fatal inherited disease in the United States and Europe,” said Verona CEO Jan-Anders Karlsson.

“More than 30,000 people in the US and more than 70,000 people worldwide are living with cystic fibrosis.”

Karlsson said two recently-approved therapies were indicated only for a subset of CF patients, and there was a need for novel, effective anti-inflammatory medications to treat the underlying inflammation in cystic fibrosis.

“RPL554 has a differentiated mechanism of action and preclinical 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."