Trial of MS1819, Yeast-based EPI Treatment, Opens 2 Sites in Poland

Two new sites for the extension of a Phase 2b trial testing an immediate release capsule form of MS1819 in treating exocrine pancreatic insufficiency in cystic fibrosis (CF) have opened in Poland and are enrolling patients by invitation.

Part of the OPTION 2 study (NCT04375878), these European sites join those already open in the U.S. in assessing the optimal dose of a yeast-based pancreatic enzyme replacement therapy (PERT) in eligible CF patients.

Their addition is intended to minimize delays in enrollment due to the COVID-19 pandemic, AzurRx BioPharma, the treatment’s developer, announced.

“Overall, the OPTION 2 trial of MS1819 is proceeding ahead of schedule, and we look forward to reporting topline data in the first quarter of 2021,” James Sapirstein, president and CEO of AzurRx, said in a press release.

Thick and sticky mucus forms in various organs in CF patients, including the lungs, where it raises the risk of infections, and the digestive system, where it hinders the release of the digestive enzymes from the pancreas needed to break down food, particularly fats. This loss or deficiency in pancreatic enzymes affects the absorption of essential nutrients.

The current standard treatment for the exocrine pancreatic insufficiency (EPI) that results is porcine-derived pancreatic enzyme replacement therapy (PERT). Pancreatic enzymes derived from pigs are used to effectively replace the missing pancreatic enzymes in a patient’s digestive tract.

But as a porcine-derived treatment, this PERT carries a risk of transmitting animal pathogens and raises concerns over the use of animal products.

The active ingredient of MS1819 is a synthetic, fat-cleaving enzyme — called lipase — derived from yeast cells. Given as an oral capsule, it is coated with a polymer resistant to degradation in the stomach, allowing the therapy to reach the intestines. There, the enzyme helps to break down fat molecules so that they can be absorbed.

“MS1819 has the potential to redefine the treatment of exocrine pancreatic insufficiency, a debilitating gastrointestinal condition common to patients with cystic fibrosis that can lead to a chronic nutritional deficiency,” Sapirstein said.

AzurRx believes MS1819 could improve patients’ quality of life, as well as their adherence to this therapy. It aims to lower the number of pills needed for effective treatment, and to come as an easier to swallow, smaller capsule.

“The goal of the MS1819 program is to provide cystic fibrosis patients with a safe and effective therapy that enables them to control EPI and achieve the nutrition necessary for healthy growth, weight maintenance, and good lung function,” Sapirstein said.

“The recently initiated extension [trial] arm … provides the opportunity to investigate an immediate-release capsule formulation of MS1819, which we believe could offer important advantages to cystic fibrosis patients in their daily management of EPI,” he added.

OPTION 2 is an open-label, crossover clinical trial assessing the safety, tolerability, and efficacy of MS1819, against porcine-derived PERT, in 30 adults with CF.

Enrolled patients are divided into two, three-week treatment groups: one starts on standard PERT pills and the other on MS1819 enteric (delayed release) capsules at doses of 2.2 grams or 4.4 grams daily. Stool samples are then collected and analyzed to determine treatment efficacy. Each group at this point switches, or crosses over, to the other treatment (PERT or MS1819) for another three weeks.

Dosing for OPTION 2 was determined based on earlier OPTION 1 trial (NCT03746483) data.

In its extension phase, OPTION 2 is testing an immediate release version of MS1819 capsules in adult patients with EPI who completed this trial’s enteric phase. Its main goal is to identify an optimal dose and delivery method.

Dosing of patients in this extension phase began in January.