Promising Phase 1Trial on POL6014 for Cystic Fibrosis Finished

Swiss Pharmaceutical company Polyphor has successfully completed its Phase I clinical trial in healthy volunteers for the investigational inhaled POL6014.

POL6014 is a selective and reversible inhibitor of human neutrophil elastase (hNE), a key target for the treatment of respiratory diseases like cystic fibrosis (CF).

Cystic fibrosis is a genetic disease in which the lungs and digestive system can become clogged with thick, sticky mucus, resulting in breathing and digestion problem starting at a very young age. Over the course of many years, the lungs become increasingly damaged and may eventually stop working properly.

CF is characterized by abnormal transport of Cl- and Na+ across the epithelium, leading to the production of sticky mucus and neutrophil-dominated lung inflammation that becomes sustained by bacterial infections.

According to the Polyphor website, “Activated or necrotic neutrophils liberate proteases that cause damage to structural, cellular and soluble components of the pulmonary microenvironment. Neutrophil elastase is the major protease released in the lung of CF patients and plays a major role in the disease process.”

The randomized, double-blind, placebo-controlled dose-escalation Phase I clinical trial of POL6014 for CF evaluated the safety, tolerability and pharmacokinetics of inhaled single doses of the inhaled agent in healthy volunteers.

The results showed that POL6014 is well tolerated in all treatment groups, with no serious adverse events observed. The measured pharmacokinetic parameters improved uniformly with the dose administered using a customized Pari eFlow aerosol inhaler, a rapid nebulizer system appliance for the treatment of respiratory diseases such as CF.

While Phase I clinical trials are only the first step in a long process of  achieving FDA approval for a therapy, establishing  its safety, tolerability and pharmacokinetics in actual patients is a critical first step.

“We are very pleased with the outcome of the Phase I clinical study with our macrocycle drug candidate POL6014. The data confirms that the drug can be safely delivered to the human lung by inhalation,” said Dr. Leon Hooftman, CMO of Polyphor according to a press release. “Following the successful completion of this study, we have now initiated two clinical Phase Ib trials investigating the safety, pharmacokinetics, and pharmacodynamics of POL6014 in individuals with cystic fibrosis and non-cystic fibrosis bronchiectasis.”

Polyphor also announced that it has reached the first two milestones in a recent partnership with Cystic Fibrosis Foundation Therapeutics (CFFT). Under the collaboration agreement, Polyphor can accelerate the clinical development of the POL6014 inhaled elastase inhibitor in patients with cystic fibrosis.