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 nonporcine, highly purified biotechnology-derived PERT, has demonstrated significant efficacy in fat and protein malabsorption in patients with EPI 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 of the patients were required to discontinue their long-term use of porcine PERTs at the time of enrollment. Dosing started at 1 capsule of liprotamase (32,500 US Pharmacopoeia (USP) units crystallized cross-linked lipase, 25,000 USP units crystallized protease, and 3,750 USP units amorphous amylase) per meal or snack; dose could be increased based on protocol-defined parameters.
Results: A total of 215 subjects were enrolled and 214 received at least 1 dose of liprotamase (mean 5.5 capsules per day). During the study period, height, weight, and body mass index z scores and lung function as measured by forced expiratory volume in 1 second 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, well tolerated, and associated with age-appropriate growth and weight gain or weight maintenance in subjects with CF-related EPI.
*Division of Pediatric Pulmonology, Women and Children's Hospital of Buffalo, State University of New York at Buffalo
†Alnara Pharmaceuticals, Cambridge, MA
‡Hadassah University Hospital, Jerusalem, Israel
§St Luke's Children's Gastroenterology, Boise, ID.
Address correspondence and reprint requests to Drucy Borowitz, MD, Division of Pediatric Pulmonology, Women and Children's Hospital of Buffalo, State University of New York at Buffalo, 219 Bryant St, Buffalo, NY 14222 (e-mail: email@example.com).
Received 1 June, 2011
Accepted 11 August, 2011
See the Appendix for a complete list of Liprotamase 767 Study Group investigators.
www.clinicaltrials.gov registration no. 449904.
This study was supported by a grant from the Cystic Fibrosis Foundation Therapeutics, Inc, and Alnara Pharmaceuticals, Inc (a wholly owned subsidiary of Eli Lilly and Company). The study sponsor was actively involved in study design, assurance of accuracy of data collection and analysis, and interpretation of data. The manuscript authors are responsible for important intellectual content and for critical revisions of the manuscript. Editorial and administrative support for the manuscript was provided by representatives of Galen Press, Inc, and paid for by the study sponsor.
Previously presented at the North American Cystic Fibrosis Conference, Minneapolis, MN, October 15–17, 2009.
D.B. was on the CFF-Alnara Scientific Advisory Committee. Her employer, University at Buffalo Pediatric Associates (UPA), was paid for her work as the international principal investigator and consultant to Alnara Pharmaceuticals, Inc, now a wholly owned subsidiary of Eli Lilly and Company. UPA is being paid for her work as a consultant to Eli Lilly and Company and as a consultant to Abbott Laboratories. C.S. and M.C. were consultants to and L.B. was an employee of Alnara Pharmaceuticals.