Liprotamase therapy for Cystic Fibrosis patients

http://www.ncbi.nlm.nih.gov/pubmed/21876454

J Pediatr Gastroenterol Nutr. 2011 Aug 26. [Epub ahead of print]
International Open-Label Trial of Liprotamase Long-Term Safety And Support of Nutritional Status In Pancreatic-Insufficient Cystic Fibrosis Patients*
Borowitz D, Stevens C, Brettma LR, Campion M, Wilschanski M, Thompson H; for the Liprotamase 767 Study Group.
Source
*Women and Children's Hospital of Buffalo, Division of Pediatric Pulmonology, State University of New York at Buffalo, 219 Bryant Street, Buffalo, NY 14222, USA †Consultant, Alnara Pharmaceuticals, Inc ‡Alnara Pharmaceuticals, Inc, 840 Memorial Drive, Cambridge, MA 02139, USA §Hadassah University Hospital, Mount Scopus POB 24035, Jerusalem, Israel ||Idaho Pediatric Gastroenterology, 100 E. Idaho Street, Boise, ID 83712, USA. 1See appendix for complete list of Liprotamase 767 Study Group investigators.

Abstract
OBJECTIVES:
Patients with cystic fibrosis (CF) who have exocrine pancreatic insufficiency (EPI) require treatment with pancreatic enzyme replacement therapy (PERT) to maintain adequate nutrition and age-appropriate growth and weight gain. Liprotamase, a non-porcine, highly purified biotechnology-derived PERT has demonstrated significant efficacy in fat and protein malabsorption in EPI patients compared to placebo. This study of liprotamase is the first ever long-term trial of a PERT to evaluate safety and nutritional parameters.

METHODS:
This phase III 12-month open-label trial assessed the safety, tolerability and long-term nutritional effects of liprotamase treatment in -patients with CF and EPI 7 years and older. All patients were required to discontinue their long-term use of porcine PERTs at the time of enrollment. Dosing started at one capsule of liprotamase (32,500 USP U crystallized cross-linked lipase, 25,000 USP U crystallized protease, and 3,750 USP U amorphous amylase) per meal or snack;); dose could be increased based upon protocol-defined parameters.

RESULTS:
A total of 215 subjects were enrolled and 214 received at least one dose of liprotamase (mean 5.5 capsules per day). Over the study period, height, weight, and body mass index Z-scores and lung function as measured by FEV1 were stable. There were no clinically meaningful changes in laboratory tests, including levels of fat-soluble vitamins. Liprotamase was well tolerated without any significant safety concerns. Adverse events, primarily gastrointestinal, led to treatment discontinuation for 36 subjects (16.8%), most within the first 3 months.

CONCLUSIONS:
Treatment with a mean of 5.5 capsules of liprotamase per day, during meals and snacks, for up to 12 months was safe and well tolerated and was associated with age-appropriate growth and weight gain or weight maintenance in subjects with CF-related EPI.