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A New Alternative for Pancreatic Enzyme Replacement Therapy (PERT)

By Ella Balasa

Many in the CF community have experienced weight gain to some degree since starting modulator therapies in the last few years. As one of the many organ systems affected by CF, our digestive systems have been aided by the correction of CFTR proteins, but I know from personal experience as well as having the uncomfortable tummy conversations with other CF friends, we still suffer from gastrointestinal issues and exocrine pancreatic insufficiency (EPI). Not to forget, those that don’t have any modulator options don’t have any possibilities for relief from symptoms other than current pancreatic enzyme replacement therapy (PERT).

Fortunately, there is a company working in fervor to bring a new enzyme therapy option to the CF population for the treatment of EPI. Through a recombinant lipase called MS1819, derived from a yeast called Yarrowia lipolytica, AzurRx is working to improve fat absorption, reduce diarrhea, and minimize the number of pills required to manage symptoms. AzurRx is pursuing two clinical treatment pathways – a monotherapy, with the goal of entirely replacing usage of PERT with MS1819, and a combination therapy, where MS1819 is used in conjunction with PERT – especially for patients with severe EPI who are unable to achieve adequate nutrition despite being on a steady dosage of PERT.

How does this new enzyme differ from current therapy options?

All commercially available enzymes are derived from porcine (pig) pancreas. There is a significant unmet need for patients with severe EPI who are not achieving normal absorption of nutrients on standard PERT therapy. A small daily dose of MS1819 added to daily PERT intake has the potential to safely help patients meet their nutritional needs, alleviate abdominal pain, and achieve a better quality of life. This enzyme is formulated only with lipase to break down fats, not protease and amylase like other available enzyme products. In addition, this new therapy is more stable than current enzymes in acidic GI environments which is present in the CF gut. There is also no risk of transmission of animal pathogens unlike with the use of porcine enzymes where this may be a possibility. Importantly, since this enzyme product is synthetic, there is no dependence on pig herds.

What has MS1819 research and clinical trial results yielded so far and what will be the upcoming trial’s goals?

There are two completed phase 2 clinical trials examining the safety and efficacy of MS1819. In one trial, patients with chronic pancreatitis received MS1819. The highest dose significantly improved the coefficient of fat absorption (CFA) which is a measure of the effectiveness of pancreatic absorption. The second completed trial was conducted in patients with CF. Patients received three weeks of MS1819, 2240 mg/day, and then three more weeks on regular PERT therapy or reversed, with PERT therapy for the first 3 weeks instead. The CFA values were equivalent to those in the pancreatitis study dosage. Additionally, the level of nitrogen absorption in the MS1819 arm was comparable to that of porcine enzymes indicating that the need for protease in MS1819, as is used in porcine enzymes is unnecessary. Safety was excellent.

The two ongoing phase 2 trials called “Option 2” and “Combination” are both dose-escalating studies examining the efficacy of MS1819 in a head-to-head comparison with PERT. Patients enrolled in Option 2 will be dosed with MS1819 for 3 weeks and then 3 weeks of normal PERT therapy or reversed, receiving normal PERT therapy for 3 weeks and then the MS1819 therapy for 3 weeks. There will be two different dosage groups of MS1819, either 2240mg or 4480mg per day. MS1819 will be dosed using an enteric capsule for this trial – the same way as current enzyme treatment delivery. Topline data is expected in the first quarter of 2021 for this trial. The trial has completed enrollment in the US and in Poland. Recently, an extension phase has been added to this trial in which 4480mg per day and possibly 6720 mg per day will be studied using immediate-release capsules.

The Combination trial is for patients with severe EPI which is not controlled on normal PERT therapy. These patients receive their normal daily dose of PERT as well as a set mg amount of MS1819. For 15 days, they will receive a normal PERT dose plus 700 mg of MS1819 per day. For the next 15 days, they receive 1120 mg per day of MS1819 in addition to normal PERT dosage and for the final trial dose, they receive 2240 mg per day in addition to normal PERT therapy. Interim data on the first five patients in this study showed that all patients experienced an increase in the coefficient of fat absorption (CFA) and all had a reduced number of bowel movements a day. In addition, there were no safety issues. Topline Phase 2 Combination (MS1819 + PERT) therapy data is expected in the second quarter of 2021. This trial is currently enrolling in Hungary and Turkey.

Are you interested in participating?

Currently, all patients in the U.S. Option 2 trial have been enrolled. If you are interested in learning more about these trials, visit the site. You can find participating CF centers listed at the bottom of the page.

What can the CF community expect from this drug in the near future?

The search for a non-porcine enzyme replacement therapy for patients with pancreatic enzyme insufficiency has been difficult, but never the less, the goal may be in sight. AzurRx has conducted a careful and step by step Phase 2 process and found: 1. MS1819 has a dose-response; 2. Protease does not seem necessary during MS1819 therapy 3. MS1819 has excellent safety and tolerability at all doses studied; and 4. Adding MS1819 to commercial PERT treatment may offer benefits.

Dr. Jim Pennington, the Chief Medical Officer, stated “We are close to determining the correct dose and delivery capsule for a Phase 3 trial. The CF Foundation has been highly supportive and the FDA is interested in this program and willing to work with us to design a feasible Phase 3 program. The introduction of non-porcine enzyme treatment will offer a totally non-animal sourced enzyme free of potential contaminants and fewer capsules, reducing treatment burden. Personally, this has been quite rewarding work for me.”


About the Author: Ella is a director for USACFA. She is 28 years old and was diagnosed with CF at 18 months old. She has a B.S. in biology and serves on various research committees, authors journal submissions, and shares her health journey to provide a scientific voice and encourage empowerment to the CF community. She also introspectively writes about the hardship yet triumph that comes along with a chronic disease. When she is not taking care of her health, she enjoys cooking, drawing, and spending time with friends. View more of her work and experiences on her website,

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