Results of a clinical trial of ANG003, a non-porcine pancreatic enzyme replacement therapy, in people with cystic fibrosis
Sathe, Meghana ; Freedman, Steven D. ; Putman, Melissa S. ; Gallotto, Robert ; Clarkin, Marcie ; Gallotto, Danielle ; Pierzynowska, Kateryna LU
and Borowitz, Drucy
(2025)
In Journal of Cystic Fibrosis
24(6).
p.1043-1050
- Abstract
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... (More)
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 lipase significantly improves DHA+EPA and total fat absorption in a dose dependent manner. Results for ANG003 protease and amylase activity suggest that doses lower than those in current porcine-derived PERTs may be efficacious.
(Less)
- author
- Sathe, Meghana
; Freedman, Steven D.
; Putman, Melissa S.
; Gallotto, Robert
; Clarkin, Marcie
; Gallotto, Danielle
; Pierzynowska, Kateryna
LU
and Borowitz, Drucy
- organization
- publishing date
- 2025-11
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Amylase, Cystic fibrosis, Enzyme replacement therapy, Exocrine pancreatic insufficiency, Lipase, Malabsorption, Protease
- in
- Journal of Cystic Fibrosis
- volume
- 24
- issue
- 6
- pages
- 8 pages
- publisher
- Elsevier
- external identifiers
-
- scopus:105012185966
- pmid:40750484
- ISSN
- 1569-1993
- DOI
- 10.1016/j.jcf.2025.07.008
- language
- English
- LU publication?
- yes
- id
- 6f7850b5-1052-42a9-a02c-febae1a76b2d
- date added to LUP
- 2026-01-27 09:55:14
- date last changed
- 2026-01-27 09:55:30
@article{6f7850b5-1052-42a9-a02c-febae1a76b2d,
abstract = {{<p>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 lipase significantly improves DHA+EPA and total fat absorption in a dose dependent manner. Results for ANG003 protease and amylase activity suggest that doses lower than those in current porcine-derived PERTs may be efficacious.</p>}},
author = {{Sathe, Meghana and Freedman, Steven D. and Putman, Melissa S. and Gallotto, Robert and Clarkin, Marcie and Gallotto, Danielle and Pierzynowska, Kateryna and Borowitz, Drucy}},
issn = {{1569-1993}},
keywords = {{Amylase; Cystic fibrosis; Enzyme replacement therapy; Exocrine pancreatic insufficiency; Lipase; Malabsorption; Protease}},
language = {{eng}},
number = {{6}},
pages = {{1043--1050}},
publisher = {{Elsevier}},
series = {{Journal of Cystic Fibrosis}},
title = {{Results of a clinical trial of ANG003, a non-porcine pancreatic enzyme replacement therapy, in people with cystic fibrosis}},
url = {{http://dx.doi.org/10.1016/j.jcf.2025.07.008}},
doi = {{10.1016/j.jcf.2025.07.008}},
volume = {{24}},
year = {{2025}},
}