MS1819-PERT Combo Shows Benefits for CF Patients With EPI in Phase 2 Trial

MS1819, AzurRx BioPharma’s investigational treatment for exocrine pancreatic insufficiency (EPI) associated with cystic fibrosis (CF), safely increased fat absorption in the first five patients receiving the therapy alongside pancreatic enzyme replacement therapy (PERT) in a Phase 2 clinical trial.

The interim analysis also showed the combination therapy led to clinically meaningful improvements in patients’ body weight and stool consistency,  lowered the number of bowel movements and the incidence of steatorrhea  (excessive amounts of fat in the feces).

“We are thrilled to see such consistently positive responses from these initial patients in our ongoing Phase 2 combination therapy trial with MS1819,” James Sapirstein, CEO of AzurRx, said in a press release.  “We look forward to completing treatment of all patients and announcing top line data in 2021.”

MS1819 is an artificial form of lipase, an enzyme normally produced in the pancreas to help the body digest fats. The therapy, derived from the yeast Yarrowia lipolytica, is being investigated as a form of treatment for EPI and chronic pancreatitis, two conditions in which the pancreas is unable to function normally.

Taking place at several sites in Hungary, the open-label Phase 2 trial (NCT04302662) is assessing the safety, tolerability, and effectiveness of increasing doses of MS1819, in combination with a stable dose of PERT, in CF patients 12 and older with severe EPI.

The study, which is expected to enroll about 24 participants, seeks to determine if a combination therapy of MS1819 and PERT can increase fat absorption — measured by the coefficient of fat absorption (CFA) calculation — and alleviate abdominal symptoms in these patients.

Participants receive a daily dose of MS1819, starting at 700 mg, which is then increased every 15 days, first to 1,200 mg and then to 2,240 mg. This daily dose is given in combination with standard PERT.

The main goal of the study is to assess the effects of the combination therapy on CFA. Secondary goals include assessing the impact of treatment on patients’ body weight, stool consistency and weight, number of bowel movements, and presence of steatorrhea.

New data from the first five patients treated in the study showed the combination therapy increased CFA to values higher than 80%, the minimum threshold of adequate nutrition established by the U.S. Food and Drug Administration. This was seen across all MS1819 dose levels in all study visits. Before enrolling in the trial, all patients had CFA values of less than 80% (mean of 78.4%), which were indicative of fat malabsorption.

Increases in CFA also were accompanied by improvements in patients’ body weight and stool consistency, as well as reductions in the frequency of bowel movements and incidence of steatorrhea. No adverse events (side effects) have been reported in the study so far.

“To see these results in the first five patients is quite compelling. With its safety and efficacy profile, MS1819 has the potential to meaningfully improve the quality of life for many patients with severe EPI,” said James Pennington, MD, chief medical officer of AzurRx,.

“We believe that a small daily dose of MS1819, when added to their daily dose of PERT, has the potential to safely help CF patients meet their nutritional needs, decrease abdominal pain and alleviate multiple morbidities caused by severe EPI. We are excited to continue developing this exciting therapy and are committed to bringing this therapy to market,” he said.

In addition to this study, another Phase 2 trial called OPTION 2 (NCT04375878) is investigating the therapeutic potential of MS1819 in CF patients with EPI. Top-line data from both studies is expected in early 2021.