First Cystic Fibrosis Patients in U.S. Arm of Phase 2a Clinical Trial Receive RPL554

Cystic fibrosis patients in the United States have begun receiving the anti-inflammatory and airway-opening agent RPL554 in a Phase 2a clinical that started in Britain.

The therapy, developed by Verona Pharma, reduces airway inflammation and is a bronchodilator, relaxing airways so more air can get through them.

Verona started the U.S. arm of the trial (NCT02919995) two months after the first patient was dosed in Britain. The U.S. arm received a green light when the Food and Drug Administration accepted Verona’s Investigational New Drug (IND) application.

RLP554 is a first-in-class, inhaled inhibitor of the enzymes phosphodiesterase 3 and 4. Verona is developing it to treat CF and chronic obstructive pulmonary disease (COPD).

The therapy promotes the work of a protein called the CF transmembrane conductance regulator, or CFTR. The CFTR gene provides the instructions used to make the protein. Mutations of the gene render ion channels in the epithelial cells that protect the lungs dysfunctional, leading to CF.

In addition to reducing airway inflammation and relaxing airways so they will widen, RPL554 reduces airway obstruction and phlegm in the passages.

The U.S. arm of the trial will investigate the pharmacokinetics of mist-delivered RPL554 in 12 healthy volunteers. Pharmacokinetics refers to how the body affects a drug.

In addition, the American arm will assess the oral bioavailability of RPL554 — or how well a swallowed portion of the mist will work. It will also evaluate the safety and tolerability of mist-delivered doses.

Results of the trial are expected in the fourth quarter of 2017.

“We are pleased that the IND for RPL554 has been accepted by the FDA and to initiate clinical studies with RPL554 in the United States,” Dr. Jan-Anders Karlsson, Verona’s chief executive officer, said in a press release. “This study will support further development of RPL554 to address unmet clinical needs in patients suffering from COPD and other debilitating respiratory diseases.”

The first time Verona presented information on RPL554 as a promising treatment for CF was at the 28th Annual North American Cystic Fibrosis Conference in Atlanta in 2014.

At the time, the company was developing it for COPD. But Karlsson noted that “due to its mechanism of action, we expected that RPL554 might have utility in other respiratory diseases in addition to COPD and asthma, such as bronchiectasis and CF.”

“In our experiments, RPL554 increased the activity of CFTR, ion channels on the surface of cells obtained from the lining of the airway,” said Professor John Hanrahan, director of the CF Translational Research Center at McGill University in Montreal. “We will continue to examine this effect of RPL554 in further studies. Ultimately, if found effective and safe in cystic fibrosis patients, RPL554 could emerge as a new medicine for this debilitating disease.”


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