OPTION 2 Trial Testing MS1819 for EPI Posts ‘Mixed’ Topline Results

Treatment with MS1819 for exocrine pancreatic insufficiency (EPI) — when the pancreas does not release enough digestive enzymes and the body doesn’t receive proper nutrition — was found to be safe and well-tolerated among cystic fibrosis (CF) patients in the OPTION 2 trial, top-line results show.

However, MS1819 was not as effective at improving fat absorption as pancreatic enzyme replacement therapy (PERT) for most OPTION 2 participants.

This means that the trial’s main efficacy goal was not achieved.

“To summarize, the best word to describe the OPTION 2 topline results is mixed,” James Sapirstein, president, CEO, and chairman of AzurRx BioPharma, the therapy’s developer, said in a press release.

“MS1819 demonstrated itself to be safe and well-tolerated and data from OPTION 2, and other Phase 2 clinical trials, clearly demonstrate drug activity. However, OPTION 2 did not consistently meet the primary efficacy endpoint [goal],” Sapirstein said.

Mucus accumulation in CF impairs the function of organs, raises the risk of lung infections, and causes EPI by blocking the release of key enzymes from the pancreas. This results in an inability to properly digest food, such as fats.

MS1819 is AzurRx BioPharma’s synthetic fat-cleaving enzyme — called a lipase — designed to aid fat digestion in CF patients with EPI.

The ongoing Phase 2b OPTION 2 trial (NCT04375878) is comparing the safety, efficacy, and tolerability of MS1819 enteric (delayed-release) capsules with PERT, the current approach for treating EPI. Standard PERT provides digestive enzymes derived from pigs.

OPTION 2 enrolled 30 adults with CF at 15 sites in the U.S. and Poland. The trial’s primary efficacy goal of improved fat absorption was measured by the coefficient of fat absorption (CFA) at three and six weeks.

Participants were randomly assigned to receive either MS1819 — at doses of 2.24 or 4.48 grams — for three weeks followed by their standard PERT dose for another three weeks or to the reverse order of therapies. Such crossover design is intended to enable direct treatment comparisons within the same patient.

Stool samples were collected after each three-week treatment period to assess fat absorption, and patients were observed for two weeks after the end of treatment.

“Some patients were able to achieve CFA at levels beyond what is required to demonstrate non-inferiority with PERT therapies, but the majority did not,” Sapirstein said.

The trial also included an extension phase to test an immediate release MS1819 capsule so that it could be compared with the delayed-release formulation.

“The underlying cause of the drug’s uneven efficacy performance in OPTION 2, we believe, lies with the enteric capsule formulation,” Sapirstein said.

“While the enteric coating protects the capsule from breaking down in the stomach acid, it also appears to dissolve too slowly in the small intestine to release the lipase enzyme in time to aid with proper digestion and nutrient absorption,” he said.

To potentially overcome the limitations of the delayed-release capsule, AzurRx plans to develop a new MS1819 formulation similar to what is already used in existing PERT therapies.

“We are planning to pursue a new formulation for MS1819, this one a capsule filled with acid-resistant granules, or microbeads … Such a capsule would dissolve in the stomach, disperse the beads, and then pass through to the small intestine where the beads would break down and release the lipase enzyme so that it thoroughly mixes with food as it is being digested,” Sapiristein said.

Sapirstein said the company already has raised enough funding to advance MS1819 development and start a Phase 2 trial of efficacy “within the next year or so.”

“The drug’s mechanism of action is known and proven, it offers numerous therapeutic, safety and compliance advantages over today’s standard of care, and remains less cumbersome to manufacture,” he said. “Based on these factors, we believe that should this optimized formulation prove successful in the clinic — and we have every reason to believe it will — MS1819 could eventually become the gold standard treatment for EPI in patients with cystic fibrosis and chronic pancreatitis [inflammation in the pancreas].”

AzurRx also is conducting a Phase 2 trial (NCT04302662) to assess the safety and efficacy of MS1819 in combination with PERT. As of last month, the trial is fully enrolled with top-line results expected later this year.