Results of a Phase 2 trial showed that treatment with Spyryx’s investigative drug SPX-101 can improve lung function in patients with cystic fibrosis, regardless of their background genetic mutation causing the disease.
The most recent trial data will be discussed at the 41st European Cystic Fibrosis Society (ECFS) Conference, being held through June 9 in Belgrade, Serbia.
The oral presentation is titled, “A Double-Blind, Placebo-Controlled, Randomized Study of SPX-101, a Novel Peptide Modulator of ENaC Cell Surface Density in Adults With Cystic Fibrosis.”
SPX-101 is a small protein fragment that was developed to target epithelial sodium channels (ENaC) in the lungs and prevent them from taking up sodium. The drug reduces sodium absorption, allowing fluids to be retained on the airway surface, making mucus clearance an easier task.
To date, the Phase 2 trial has enrolled 46 cystic fibrosis patients who were randomized to receive 60 mg or 120 mg of SPX-101, or a placebo, twice daily via a portable nebulizer for a total of 28 days.
All participants had baseline percent predicted forced expiratory volume in 1 second (ppFEV1; a measure of lung function) of 40-80%.
The most recent data collected from 40 patients who completed the treatment revealed that SPX-101 could induce a meaningful benefit in lung function, especially with the higher dose tested.
By day 28, patients treated with 60 mg SPX-101 showed a mean difference in ppFEV1 of 3.08% compared to placebo, whereas 120 mg SPX-101 induced a mean ppFEV1 increase of 5.19%. The beneficial effects of the highest dose were detected early in the treatment course (day 7) and persisted through the treatment period.
Subgroup analysis also revealed that patients with baseline lung function above median (ppFEV1 above 55%) showed the best response to the treatment, with a significant improvement of 8.3% in mean ppFEV1 upon treatment with 120 mg SPX-101.
“This encouraging data for the first study of SPX-101 in patients gives hope to those of us who have grappled with CF as patients or providers for decades. These results make us optimistic that we have turned another corner in care for patients with cystic fibrosis,” Tim Shannon, MD, a pulmonologist and chairman of the Spyryx Board of Directors, said in a press release.
During the trial, SPX-101 was found to be safe and well-tolerated. The most common adverse events reported were increased sputum production and cough. No major impact on blood potassium was reported, with only one patient (in the SPX-101 60 mg group) experiencing a slight increase in blood potassium levels by the end of the 28 days.
“These data show that with this novel mechanism — internalization of ENaC — it is possible to inhibit ENaC in the airways without impacting potassium concentrations in the blood, and this has been a goal in research for the past 30 years,” said Isabelle Fajac, an MD and PhD, the principal investigator of the study in France, a professor at Université Paris Descartes, and vice president and president-elect of the European Cystic Fibrosis Society.
“These data are also very promising in terms of respiratory benefit gained from ENaC inhibition. I look forward to continuing the study,” Fajac added.
The team plans to further explore the potential of SPX-101 to better define the dose and target patients who may benefit the most with this treatment.
The clinical trial is still enrolling participants. It’s expected to include up to 90 adult CF patients at 21 clinical sites across Canada, the U.K., Portugal, and France.
Those interested in participating in the trial should visit the official clinical trial web page here.
“We’re looking forward to completing Phase 2 and beginning preparations for Phase 3 development activities in 2019,” Shannon said.