Results of a clinical trial of ANG003, a non-porcine pancreatic enzyme replacement therapy, in people with cystic fibrosis

作者：Meghana Sathe, Steven D. Freedman, Melissa S. Putman, R. Gallotto, Marcie Clarkin, Danielle Gallotto, Kateryna Pierzynowska, Drucy Borowitz · 发表于：Journal of Cystic Fibrosis · 年份：2025 · DOI：10.1016/j.jcf.2025.07.008 · 被引用次数：3 · 研究领域：Pancreatitis Pathology and Treatment、Enzyme Production and Characterization、Cystic Fibrosis Research Advances

BACKGROUND: Pancreatic enzyme replacement therapy (PERT) prevents malnutrition in people with exocrine pancreatic insufficiency, including those with cystic fibrosis (CF). We developed a lipase that is stable against proteolysis and at the pH of the fed stomach, so it can be taken during a meal to promote mixing of enzyme and substrate. We designed a dose-ranging study of ANG003, a microbial PERT combining this lipase with low pH-stable protease and amylase, also of microbial origin. METHODS: This was a multicenter, randomized evaluation of ANG003 in subjects with CF, studied once without PERT and again after randomization to a single dose level of four possible combinations of lipase, protease, and amylase. We developed blood-based substrate absorption challenge tests employing DHA+EPA, whey and potato starch to determine dose-response to each of these enzymes, respectively. RESULTS: ANG003 improved DHA+EPA absorption with a statistically significant increase with 80 mg and 120 mg lipase doses compared to 20 mg (p = 0.03; p = 0.004). The absorption of total fats followed a similar pattern to DHA+EPA. There was a significant increase in absorbed amino acid equivalents, reflecting proteolysis, over no PERT in the highest (75 mg) dose of protease (p = 0.03). In subjects without diabetes, glucose was slightly lower while c-peptide levels remained unchanged with all amylase doses. Adverse events were mild and transient. No serious adverse events occurred. CONCLUSIONS: ANG003 lipa...