Dosing Begins in Extension Study of Yeast-derived Treatment for EPI

The first two patients have been dosed in the Phase 2b OPTION 2 extension study evaluating MS1819 in treating exocrine pancreatic insufficiency (EPI) in people with cystic fibrosis (CF), its developer, AzurRx BioPharma, announced in a press release.

The thick mucus that accumulates in the organs of people with CF, including the pancreas, can prevent the pancreas from releasing enzymes that are necessary for proper food digestion, resulting in EPI.

EPI is generally treated with pancreatic enzyme replacement therapy (PERT), wherein digestive enzymes — usually collected from animals such as pigs — are administered to replace the missing enzymes.

MS1819 contains a synthetic, fat-cleaving enzyme (lipase) derived from yeast cells; as such, it avoids potential concerns and sensitivities related to the use of animal products. According to AzurRx, MS1819 also has the potential to improve patient compliance and quality of life, given that pill burden and pill size may be reduced relative to conventional PERT.

The ongoing OPTION 2 trial (NCT04375878), which aims to enroll 30 CF patients ages 18 and older, is comparing MS1819 to traditional porcine (pig-derived) PERT at two doses, 2.2 grams or 4.4 grams. Trial participants are being treated with either MS1819 (at their assigned dose) or porcine PERT for three weeks before switching to the other therapy, with safety and efficacy measures taken after each treatment. This crossover design allows for direct treatment comparisons within the same patient.

OPTION 2 may still be recruiting eligible adults at sites in the U.S. and Poland; information is available here. The trial was initially using enteric (delayed release) capsules of MS1819, but a new trial arm has been added to test immediate release capsules of the investigational therapy.

Its extension study is evaluating MS1819 in people who have already completed the OPTION 2 crossover trial. The two people now being dosed were given immediate release capsules of MS1819 at higher doses than were used in the earlier OPTION 1 study (AzurRx did not specify exact dosages).

Results from the OPTION2 crossover trial are expected by the close of March, and those of its extension study by the close of June.

“Due to enrollment in the initial crossover trial being ahead of schedule, we are given an opportunity to thoroughly explore optimal doses and capsule types that will help guide our future development plans for MS1819 in a Phase 3 program,” James Pennington, MD, chief medical officer of AzurRx, said. “In the meantime, we will continue our preparation for a successful FDA meeting later this year.”

No safety concerns regarding the study’s updated design and protocol were found by its data monitoring committee, Pennington added.

AzurRx is also sponsoring a separate Phase 2 clinical trial (NCT04302662) that is testing escalating doses of MS1819 in combination with traditional PERT.

According to the Cystic Fibrosis Foundation, more than 30,000 patients in the U.S. have EPI due to CF.