Verona Pharma Reports Positive Top-Line Data from Phase 2a Trial with RPL554 in Cystic Fibrosis Pati

RPL554 demonstrates a favorable pharmacokinetic and pharmacodynamic profile in cystic fibrosis patients

LONDON, UK I March 02, 2018 I Verona Pharma plc (AIM:VRP) (Nasdaq:VRNA) (“Verona Pharma”), a clinical-stage biopharmaceutical company focused on developing and commercializing innovative therapies for respiratory diseases, announces today that top-line data from its Phase 2a trial with nebulized RPL554 demonstrate that the investigational therapy has a favorable pharmacokinetic (PK) and pharmacodynamic (PD) profile, with single doses achieving statistically significant (P<0.05) increases in average forced expiratory volume in one second (FEV1) in patients with cystic fibrosis (CF). These data provide a solid foundation for further development of RPL554 for the treatment of CF.

RPL554 is a first-in-class, inhaled, dual inhibitor of the enzymes phosphodiesterase 3 and 4 designed to have anti-inflammatory as well as bronchodilator properties, and is currently in development for the maintenance treatment of COPD and for the treatment of CF. RPL554 has anti-inflammatory effects, and in pre-clinical studies, has been observed to stimulate the CF transmembrane conductance regulator (CFTR), a protein whose mutation results in dysfunctional ion channels in epithelial cells, leading to CF. Based on available data, RPL554 has the potential to enhance mucociliary clearance (reduce phlegm in the airways), reduce airway obstruction and inhibit inflammation.

“Achieving a six percent sustained improvement from baseline in FEV1 after a single dose is very impressive in this group of CF patients,” according to the trial’s lead investigator, Professor Andres Floto, Wellcome Trust Senior Investigator, and Research Director of the Department of Medicine, University of Cambridge and Papworth Hospital, UK.

“These top-line findings demonstrate a favorable pharmacokinetic profile of inhaled RPL554 in CF patients, which is consistent with our earlier findings in COPD,” said Jan-Anders Karlsson, PhD, CEO of Verona Pharma. “While we believe these results support further development of the drug in CF, we await the results of our ongoing Phase 2b trial for the maintenance treatment of COPD, for which we anticipate reporting top-line data early in the second quarter of 2018, to prioritize the future therapeutic focus of RPL554 development.

Trial details

This Phase 2a trial evaluated the PK and PD profile, and tolerability of RPL554 in 10 patients with CF, at 1.5 mg and 6.0 mg doses as compared to placebo. Patients displayed a range of CF genotype mutations in the CFTR.

Primary endpoint measure:

  • Pharmacokinetics of single nebulized doses of RPL554 in 10 patients with CF: - The PK profile was consistent with that observed in patients with COPD, although with lower peak serum levels of RPL554 in CF patients; and - Serum half-life was dose-dependent; 7.5 to 10.1 hours for 1.5 mg and 6 mg, respectively.

Secondary endpoint measures:

  • The drug also elicited a statistically significant increase in average FEV1 in treated patients for 1.5 mg (all P<0.01) and 6 mg (all P<0.05) at 4, 6 and 8 hour time points;

  • The drug was well-tolerated in this patient group with an adverse event profile consistent with other studies with RPL554.

The trial was conducted at Papworth Hospital, UK, one of the largest specialist cardiothoracic hospitals in Europe, and was supported by the UK Cystic Fibrosis Trust pursuant to the second Venture and Innovation Award received by Verona Pharma in October 2016.

“We’re pleased to see these interesting results come through, and that our investment in this area continues to show promise. We look forward to seeing the next steps of developing RPL554 for the treatment of cystic fibrosis” said Janet Allen, Director of Strategy and Innovation at the Cystic Fibrosis Trust.

About Cystic Fibrosis

CF is the most common fatal inherited disease in the United States and Europe. CF causes impaired lung function and is commonly associated with repeat and persistent lung infections due to the inability to clear thickened mucus from the lung. This condition often results in frequent exacerbations and hospitalizations. There is no cure for CF and the median age of death for CF patients is around 40 years. CF is considered a rare, or orphan, disease by both the U.S. Food and Drug Administration and the European Medicines Agency. According to the Cystic Fibrosis Foundation, more than 30,000 people in the United States and more than 70,000 people worldwide are living with CF and approximately 1,000 new cases of CF are diagnosed each year. CF patients require lifelong treatment with multiple daily medications, frequent hospitalizations and, ultimately, lung transplants in some end-stage patients. The quality of life for CF patients is compromised as a result of spending significant time on self-care every day and frequent outpatient doctor visits and hospitalizations. CF patients take an average of seven medications daily.

About Verona Pharma plc

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 clinical trials, treatment with RPL554 has been observed to result in statistically significant improvements in lung function as compared to placebo, and has shown clinically meaningful and statistically significant improvements in lung function when administered in addition to frequently used short- and long-acting bronchodilators as compared to such bronchodilators administered as a single agent. Verona Pharma is developing RPL554 for the treatment of chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and potentially asthma.

SOURCE: Verona Pharma

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