Trial Enrolling Patients With Severe Digestive Enzyme Deficiency in Europe

A Phase 2 clinical trial investigating MS1819 in combination with stable pancreatic enzyme replacement therapy (PERT) to treat exocrine pancreatic insufficiency (EPI) in people with cystic fibrosis (CF) is actively recruiting participants in Europe, AzurRx BioPharma, the treatment’s developer, announced.

The open-label study (NCT04302662) expects to enroll 24 CF patients, ages 12 and older, with severe EPI who failed to respond fully to PERT alone.

According to AzurRx, enrollment is open at eight of the trial’s 12 expected clinical sites. Hungary has six sites active and has begun dosing, and two sites recently opened it Turkey, where patient screening is underway. Contact information for the study, expected to end by June 2021, is available here.

“We are truly pleased and encouraged by the interest in our expanding global Phase 2 Combination Trial,” James Pennington, MD, chief medical officer of AzurRx, said in a press release.

EPI, a deficiency in exocrine pancreatic enzymes necessary to digest the fats, proteins, and carbohydrates in food, is common in CF. It makes digestion difficult and often leads to gastrointestinal (GI) discomfort.

CF patients with EPI are prescribed PERTs to replace the missing digestive system enzymes.

While a daily stable PERT dose eases digestion, adequate absorption of fat, because it is the most difficult nutrient to digest, can be lacking despite the treatment.

MS1819 is a lab-made form of lipase, an enzyme normally produced in the pancreas to help the body digest fats. This enzyme is derived from the yeast Yarrowia lipolytica, and contains no animal products. PERTS are typically derived from pigs.

MS1819 is taken orally as an enteric capsule, or one coated in a polymer that prevents its breakdown in the stomach. This coating helps to ensure the therapy is released only when the capsule reaches the intestines.

A combination of MS1819 and PERT may boost nutrient absorption in CF patients with severe EPI who inadequately respond to PERT alone.

Those enrolled in the Phase 2 trial will be given increasing doses of MS1819 on top of a stable dose of PERT. Dosing of  MS1819 will start at 700 mg, before increasing every 15 days to 1,200 mg, followed by 2,240 mg. Treatment will be maintained from 39 to 51 days (between one and two months), and patients will be followed for up to nearly 3 months (81 days).

The trial’s main goals are to evaluate the combination’s safety and, for efficacy, to assess how much fat is absorbed and how much expelled— measured by the coefficient of fat absorption (CFA) — over three days as patients are given high-fat meals.

Recent interim data covering five patients showed that the combination therapy increased CFA above 80%, the minimum threshold of adequate nutrition established by the U.S. Food and Drug Administration. Before enrolling in the trial, patients’ average CFA was 78.4%, indicative of fat malabsorption.

The rise in CFA was seen across all MS1819 dose levels analyzed.

The combo therapy also improved patients’ body weight and stool consistency, and reduced the frequency of bowel movements and incidence of steatorrhea (excess fat in feces). No adverse events were reported.

“The recently reported interim data suggests promising results, and the full data readout is expected in the second quarter of next year,” Pennington said.

“Our investigators in Turkey have been extremely diligent in driving the start-up of this trial in a very efficient and effective manner, and we look forward to our continued work with them,” he added.