抽象的

A comparison of liprotamase, a non-porcine pancreatic enzyme replacement therapy, to porcine extracted pancrelipase in a noninferiority randomized clinical trial in patients with cystic fibrosis

Michael W Konstan, Jeffrey S Wagener, Michael Wilschanski, István Laki, Steven R Boas, Dorota Sands, Monica Gangal, Renee S Martin, William Shanahan, James Pennington

Objective: Porcine derived enzymes are used for pancreatic enzyme replacement therapy in patients with cystic fibrosis (CF). Liprotamase is a biotechnology-derived, non-porcine, enzyme replacement without enteric coating. This study compared the effects of liprotamase and porcinederived pancrelipase on Coefficient of Fat Absorption (CFA) in patients with Exocrine Pancreatic Insufficiency (EPI) due to CF.

Methods: We conducted a randomized, open-label, assessor blind, parallel group, multicenter, international trial to evaluate the noninferiority of liprotamase to porcine pancrelipase in 128 CF patients’ age ≥7 years with pancreatic insufficiency (Study NCT02279498). Subjects were randomized to liprotamase or pancrelipase, dose-matched to pre-study lipase doses. The primary endpoint was the between group difference in least square (LS) mean change from baseline in CFA, with a non-inferiority margin of -15% for the lower bound of the 95% confidence interval (CI). Key secondary endpoints compared treatment effects on CFA in the absence or presence of concomitant gastric acid suppression (GAS), and coefficient of nitrogen absorption (CNA).

Results: Liprotamase missed the noninferiority criterion for CFA (95% CI -16.0, -7.7%), but met that criterion for CNA (95% CI -1.9, -0.7%). Concomitant GAS was associated with higher CFA with liprotamase but not pancrelipase.

Conclusion: In this study, liprotamase was inferior to pancrelipase with regards to CFA, but not CNA. Higher doses and GAS may improve the efficacy of liprotamase.