"The U.S. Food and Drug Administration today announced the approval of Lumizyme (alglucosidase alfa) for treatment of patients with infantile-onset Pompe disease, including patients who are less than 8 years of age. In addition, the Risk Evaluatio"...
Mechanism Of Action
The pancreatic enzymes in ULTRESA catalyze the hydrolysis of fats to monoglycerides, glycerol and free fatty acids, proteins into peptides and amino acids, and starches into dextrins and short chain sugars such as maltose and maltotriose in the duodenum and proximal small intestine, thereby acting like digestive enzymes physiologically secreted by the pancreas.
The pancreatic enzymes in ULTRESA are enteric-coated to minimize destruction or inactivation in gastric acid. ULTRESA is designed to release most of the enzymes in vivo at pH greater than 5.5. Pancreatic enzymes are not absorbed from the gastrointestinal tract in appreciable amounts.
Study 1 was a randomized, double-blind, placebo-controlled, crossover study of 31 patients, ages 8 to 37 years, with exocrine pancreatic insufficiency due to cystic fibrosis. The final analysis population was limited to 24 patients, who completed both treatment periods and had stool results available for each treatment period. Patients were randomized to receive ULTRESA (at a dose not to exceed 2,500 lipase units per kilogram per meal or snack) or matching placebo for 6 to 7 days of treatment followed by crossover to the alternate treatment for an additional 6 to 7 days. The mean dose during the controlled treatment periods was 6,270 lipase units per kilogram per day. All patients consumed a high-fat diet (2 grams of fat per kilogram of body weight per day) during the treatment periods.
The coefficient of fat absorption (CFA) was determined by a 72-hour stool collection during both treatments, when both fat excretion and fat ingestion were measured. Each patient's CFA during placebo treatment was used as their no-treatment CFA value.
Mean CFA was 89% with ULTRESA treatment compared to 56% with placebo treatment. The mean difference in CFA was 35 percentage points in favor of ULTRESA treatment with 95% CI: (25, 45) and p < 0.0001.
Subgroup analyses of the CFA results showed that mean change in CFA was greater in patients with lower no-treatment (placebo) CFA values than in patients with higher no-treatment (placebo) CFA values. There were similar responses to ULTRESA by age and gender.
The coefficient of nitrogen absorption (CNA) was determined by a 72 hour stool collection during both treatments, when nitrogen excretion was measured and nitrogen ingestion from a controlled diet was estimated (based on the assumption that proteins contain 16% nitrogen). Each patient's CNA during placebo treatment was used as their no treatment CNA value.
In Study 1, mean CNA was 84% with ULTRESA treatment compared to 59% with placebo treatment. The mean difference in CNA was 26 percentage points in favor of ULTRESA treatment with 95% CI: (18, 33) and p < 0.0001.
Study 2 was an open-label study of 9 patients, ages 7 years to 11 years (mean 10 years), with exocrine pancreatic insufficiency due to cystic fibrosis. The final analysis population was limited to 7 patients who completed both the washout and treatment phases of the study. After a 15 day screening period on individually-titrated doses of ULTRESA not to exceed 2,500 lipase units per kilogram per meal, patients in Study 2 entered a 7-day washout phase (no treatment) before returning to a 12-day treatment phase on the same individually-titrated dose of ULTRESA. The mean daily dose of ULTRESA during the treatment phase was 6,846 lipase units per kilogram body weight per day. All patients consumed a high-fat diet (2 grams of fat per kilogram of body weight per day) during both the washout phase and the treatment phase.
The mean coefficient of fat absorption (CFA) was determined during the washout phase (no treatment) and during the ULTRESA treatment phase. Mean CFA was 35% during the washout phase and was 83% during the ULTRESA treatment phase.
Last reviewed on RxList: 10/14/2014
This monograph has been modified to include the generic and brand name in many instances.
Additional Ultresa Information
Report Problems to the Food and Drug Administration
Find out what women really need.