SILVER SPRING, Md. – A federal advisory panel on Jan. 12 voted 7 to 4, with 1 abstention, that the potential risks of liprotamase, a genetically engineered pancreatic enzyme formulation, outweighed its benefits as a treatment for exocrine pancreatic insufficiency.
Liprotamase – which contains lipase, protease, and amylase and is available in capsule form and in one strength only – is being reviewed by the Food and Drug Administration for the treatment for patients with exocrine pancreatic insufficiency (EPI) caused by cystic fibrosis (CF), chronic pancreatitis (CP), pancreatectomy, or other conditions that limit or impair function of the pancreas; this indication was proposed by the manufacturer, Alnara Pharmaceuticals. If approved, liprotamase would be the first nonporcine-derived pancreatic enzyme therapy available in the United States. Porcine-derived pancreatic enzyme products have been available for years; currently, three such products are approved.
At the meeting of FDA’s Gastrointestinal Drugs Advisory Committee, the majority of the panelists agreed that the data from the pivotal trial, which compared liprotamase (32,000 U) per meal to placebo in 138 patients with CF-related EPI over 6 weeks did not provide enough evidence for efficacy. The primary end point was changes from baseline in the coefficient of fat absorption (CFA), a measure of the amount of dietary fat absorbed that has been accepted as a surrogate end point for the porcine-derived products, because an increase in fat absorption has been associated with improvements in clinical outcomes.
In the study, the CFA increased by 11% among those on treatment, compared with 0.2% among those on placebo. The panel voted 10 to 1, with 1 abstention, that the magnitude of the change in CFA among those on liprotamase was not sufficient to be clinically meaningful. Panelists also observed that the magnitude of the effect on CFA with liprotamase did not appear to be as good as with porcine products, although they acknowledged that there was an unmet need for an alternative to those products, particularly for children and adolescents.
All but one of the panel members recommended that more studies on the efficacy of the liprotamase should be conducted before approval, including studies that directly compared it with porcine products and measured effects of treatment on height, weight, and body mass index over time, as well as the effect on symptoms such as flatulence, steatorrhea, and stool frequency, and on quality of life measures.
The panel was not asked specifically vote on whether to recommend approval.
The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest by the FDA prior to the meeting. Occasionally, the FDA grants a waiver to a panelist with a conflict, but not at this meeting.