Adrulipase found safe but may miss main efficacy goal in CF trial
CF treatment is failing to aid patient digestion in Phase 2 study: Data
A new adrulipase formulation for people with cystic fibrosis (CF), designed as a treatment for exocrine pancreatic insufficiency or EPI — when the small intestine is unable to fully digest food due to problems with digestive enzymes from the pancreas — was deemed safe and well tolerated in a Phase 2 clinical trial, according to top-line data.
But while the new therapy from First Wave BioPharma showed an improvement over prior formulations of adrulipase, the preliminary data suggest that the trial’s primary efficacy goal was not met. That goal is a change in the coefficient of fat absorption or CFA, a measure of how well the body is absorbing fats from food.
In the optimized formulation, adrulipase — a fat-digesting enzyme derived from yeast — is packed in microgranules, or tiny particles, to allow it to resist the acid environment of the stomach and reach the small intestine.
First Wave says it will continue to analyze the data from its SPAN trial regarding its primary and secondary goals in the coming weeks. Those goals involve stool weight, signs and symptoms of poor nutrient absorption, called malabsorption, and coefficient of nitrogen absorption, a parameter that assesses how well the body is absorbing proteins. Additional results are expected in about two months.
“We are in the process of analyzing the dataset and anticipate having a topline review of the primary and secondary endpoints in the September timeframe,” James Sapirstein, president and CEO of First Wave BioPharma, said in company press release.
Phase 2 SPAN trial tested safety, efficacy of new CF treatment formulation
With the trial’s completion, and following the analysis, the company plans to meet with the U.S. Food and Drug Administration later this year. The aim there, according to First Wave, is to review the data with regulators and discuss the design of a registrational Phase 3 study — one that aims to obtain sufficient data to support regulatory approval of the CF treatment.
The open-label SPAN trial (NCT05719311), launched earlier this year, enrolled 13 adults with CF at three sites in the U.S. In an open-label study, both participants and researchers know who is receiving a medication, and its dose.
Here, each patient received a low dose of oral adrulipase for three weeks. Patients who failed to respond well to the treatment received a medium dose of adrulipase, and then a high dose if needed.
Besides the lung function impairment that’s the hallmark of CF, the thick, sticky mucus that builds up in patients also can affect the pancreas. As a result, the release of pancreatic enzymes required for breaking down food in the intestines, especially fats, is blocked, leading to EPI.
Patients often require pancreatic enzyme replacement therapy, known as PERT, that supplies the needed enzymes. Available PERTs typically are derived from pigs.
Sapirstein noted that the trial found that the company’s “enhanced microgranule delivery formulation of adrulipase was safe and well tolerated.”
“We would like to thank the patients who volunteered to participate in the study and the investigators and their staff at our three participating clinical trial sites for ensuring that the trial was fully enrolled and completed on time,” Sapirstein said.