Dosing begins in trial of adrulipase, yeast-derived enzyme for EPI

The first two patients have been dosed in the SPAN clinical trial testing a new formulation of adrulipase, a yeast-derived enzyme, to treat exocrine pancreatic insufficiency (EPI) in adults with cystic fibrosis (CF).

The open-label Phase 2 study (NCT05719311) is enrolling adult patients at three sites, one each in Florida, Illinois, and Nevada. Those eligible are currently using pancreatic enzyme replacement therapy (PERT) and have a coefficient of fat absorption — CFA, a measure of the percentage of fat absorbed from the diet — of at least 80%. A CFA above 80% is considered the minimum for a therapeutic effect in CF patients with EPI.

“With dosing initiated, we now look forward to a top-line data readout from the Phase 2 SPAN trial by mid-2023, which we hope will confirm the favorable results” of previous testing, James Sapirstein, president and CEO of First Wave BioPharma, said in a company press release.

In people with CF, thick mucus accumulates in multiple organs, including the pancreas. The mucus also prevents the pancreas from releasing enzymes required for digestion, particularly of fats.

PERT is the standard treatment for EPI, where enzymes are used to aid digestion and nutrient absorption. These enzymes are typically derived from pigs.

Adrulipase is a fat-digesting enzyme, also known as lipase, extracted from yeast instead of animals. Given orally, the enzyme is packed in microgranules that prevent its degradation in the acidic environment of the stomach, allowing it to reach the small intestine where fats are broken down.

This packaging also may allow for lower daily doses than those used in current treatments, the company has stated.

“EPI is a debilitating gastrointestinal condition common to patients with CF that can result in numerous, life-altering complications, including malnutrition,” said Steven Boas, MD, founder of the Cystic Fibrosis Research Institute and Cystic Fibrosis Center of Chicago.

“A safe and effective therapy that allows individuals with cystic fibrosis to gain control over EPI, while diminishing the daily pill burden required with PERT, is an important medical need that would have a profound impact on the lives of patients,” he added.

The trial aims to assess the safety, tolerability, and efficacy of this adrulipase formulation in 12 CF patients.

Patients will switch from a commercial PERT to adrulipase, starting on a low dose. If EPI symptoms persist for three days or more, they will be moved to a medium dose and, if necessary, to the investigative treatment’s high dose. Safety will be evaluated one week after the three-week treatment period.

The trial’s main efficacy goal is to measure changes in CFA. Additional goals include assessing stool weight, malabsorption, and the coefficient of nitrogen absorption, a marker of protein absorption.

“We are encouraged by the current pace of enrollment … which we hope will be a first step towards providing patients with a safe and effective therapy that allows individuals with CF to gain control over EPI, while diminishing the daily pill burden required with porcine-derived pancreatic enzyme replacement therapy (PERT),” Sapirstein said in a separate company release.

In addition to EPI in CF patients, adrulipase is being developed as a possible treatment of chronic pancreatitis, a condition marked by damage to the pancreas due to inflammation.