Pancreatic Enzyme Product Research Articles

Comparison of two pancreatic enzyme products for exocrine insufficiency in patients with cystic fibrosis

BackgroundZenpep (APT-1008) is a pancreatic enzyme product for the treatment of exocrine pancreatic insufficiency (EPI) associated with cystic fibrosis (CF). MethodsZenpep and Kreon, both containing 25,000 lipase units, were compared in a randomised, double-blind, crossover, non-inferiority study for CF-associated EPI in patients aged ≥12years. Patients on a standardised diet and stabilised treatment were randomised to two treatment sequences: Zenpep/Kreon or Kreon/Zenpep. The primary efficacy endpoint was the coefficient of fat absorption over 72h (CFA-72h). Results96 patients (mean age 19.2years, 60.4% males) were randomised with 83 completers of both sequences comprising the efficacy population. Zenpep demonstrated non-inferiority and equivalence to Kreon in fat absorption (LS mean CFA-72h: Zenpep, 84.1% [SE 1.1] vs. Kreon, 85.3% [SE 1.1]; p=0.297). Safety and tolerability were similar. ConclusionsZenpep is comparable with Kreon in efficacy and safety for the treatment of adolescents and adults with CF-associated EPI.NCT01641393

240 A randomized, double-blind, multicentre, multinational crossover comparison of the pancreatic enzyme product (PEP) APT-1008 (ZENPEP®) to KREON® in the treatment of exocrine pancreatic insufficiency (EPI) associated with cystic fibrosis (CF) in patients ≥12 years of age

Objectives An investigational PEP (APT-1008, to be marketed in Europe as ENZEPI®) was compared to KREON® in the treatment of EPI associated with CF. Methods This was a randomized, double-blind, active-controlled, 2-arm crossover, multinational, multicentre study comparing APT-1008 (APT) to KREON in the treatment of EPI in patients ≥12 years of age with CF. Patients were stabilized on their current PEP treatment during screening followed by randomization to APT or KREON for 28 days; then switched without washout to the opposite treatment with the same treatment schedule. The primary efficacy endpoint was the coefficient of fat absorption over 72 hours (CFA-72h) at the end of each period. Secondary endpoints included the coefficient of nitrogen absorption over 72 hours, clinical signs and symptoms of EPI, and quality of life. Safety assessments included adverse events (AE), laboratory tests and vital signs. Results 96 patients were randomized into 2 treatment sequences (APT/KREON or KREON/APT) with 83 completers comprising the efficacy population. APT demonstrated both non-inferiority and equivalence to KREON in fat absorption (LS mean CFA-72h: APT 84.08% [SE 1.109] vs. KREON 85.33% [SE 1.109]). Efficacy results of APT and KREON were generally similar for the secondary endpoints. The most frequent AEs were gastrointestinal, in 8.7% and 11.1% of patients on APT and KREON, respectively; no treatment-related serious AEs occurred. APT demonstrated safety and tolerability similar to KREON. Conclusions This study demonstrated that APT has comparable efficacy and safety to KREON in the treatment of adolescents and adult patients with EPI associated with CF.

The FDA and prescription pancreatic enzyme product cost.

The FDA and prescription pancreatic enzyme product cost.

Efficacy of a Novel Pancreatic Enzyme Product, EUR-1008 (Zenpep), in Patients With Exocrine Pancreatic Insufficiency Due to Chronic Pancreatitis

EUR-1008 (ZENPEP® [pancrelipase] Delayed-Release Capsules) delayed-release capsules is a novel, enteric-coated, porcine-derived pancreatic enzyme product. This study evaluated the efficacy and safety of 2 doses of ZENPEP in patients with chronic pancreatitis (CP) and exocrine pancreatic insufficiency (EPI). The effect of ZENPEP on the coefficient of fat absorption (CFA) was investigated in a randomized, double-blind, dose-response, crossover study with placebo run-in (7-9 days) and 2 treatment periods (9-11 days) composed of a high dose (7 × 20,000 lipase units per day) and a low dose (7 × 5000 lipase units per day). Mean CFA was significantly higher with low- (88.9%) and high-dose (89.9%) ZENPEP versus placebo run-in (82%; P < 0.001; n = 72) with no difference between doses (P = 0.228, primary end point). In patients with baseline CFA less than 90% (n = 33), the high dose was significantly more effective (CFA: 84.1%) than the low dose (CFA: 81.1%; P < 0.001). Post hoc analysis revealed an increase in treatment effect with more severe EPI. Coefficient of nitrogen absorption (P < 0.001), body weight (P ≤ 0.021), and body mass index (P ≤ 0.020) also increased significantly with both doses compared with baseline. Percentage of days with EPI symptoms decreased with both doses. Our findings suggest that CP patients with EPI benefit from a low dose of ZENPEP, whereas the high dose might be needed for patients with more severe EPI.

Use of a Mutilumen Catheter to Assess the Bioavailability of an Enteric- Coated High-Buffered Pancrelipase Formulation in Patients with Exocrine Pancreatic Insufficiency

Treatment of exocrine pancreatic insufficiency (EPI) secondary to conditions including cystic fibrosis or chronic pancreatitis requires exogenous supplementation with a specially formulated pancreatic enzyme product (PEP). The FDA has mandated that the intestinal bioavailability of these preparations be evaluated in vivo in patients. This pilot clinical study examined the feasibility of using a multi-lumen catheter with an occluding balloon to measure changes in intraduodenal enzyme concentrations following oral administration of a PEP. In this two arm cross-over study, patients with mild-severe EPI were administered enteric coated (EC) highbuffered pancrelipase or placebo capsules with a liquid Lundh meal. Gastric and duodenal samples were aspirated at 15-minute intervals over 3 hours in each treatment arm. The concentrations of three pancreatic enzymes (lipase, amylase, and protease) were measured in the collected fluids. The maximum concentration (Cmax), and area under the duodenal enzyme concentration vs. time profile (AUC) were determined. Comparison of enzyme concentrations between placebo and treatment phases demonstrated appreciable increases in all three enzymes in the subject with cystic fibrosis (CF+), but only a modest increase in the subject with mild-to-moderate EPI (CF-). During the EC-high-buffered pancrelipase+meal phase, the fold increase in the Cmax of lipase, amylase, and protease concentrations compared to the placebo+meal phase in subject CF- were 0.96, 1.65, and 1.64, respectively. In subject CF+, who had severe pancreatic enzyme insufficiency, the fold increase in the AUC of lipase, amylase and protease concentrations compared to the placebo+ meal phase was 66.1, 15.9, and 651, respectively. Time to peak concentration occurred earlier during the active treatment phase. In both subjects and both treatments a peak duodenal pH of 8 was measured. The catheter employed in this study can be used to determine bioavailability of PEPs in severe EPI in a single day pretreatment vs. post treatment setting (NCT00744250).

Axcan Offers to Acquire Eurand to Accelerate its Speciality Pharma Business

The Independent Directors of the speciality pharmaceutical company Eurand, acting on behalf of the company’s Board, have approved an acquisition agreement under which Axcan Holdings will buy Eurand for US$12.00 per share in cash in a deal worth US$583 M. Axcan will gain complete control of Eurand’s approved pancreatic enzyme product (PEP) Zenpep® (pancrelipase), thereby strengthening its PEP portfolio.

Evaluation of an Enteric-Coated Buffered Pancreatic Enzyme Product in Cystic Fibrosis Patients with Gastrostomy Tubes

Evaluation of an Enteric-Coated Buffered Pancreatic Enzyme Product in Cystic Fibrosis Patients with Gastrostomy Tubes

EUR-1008 pancreatic enzyme replacement is safe and effective in patients with cystic fibrosis and pancreatic insufficiency

Background EUR-1008 (Zenpep™ [pancrelipase]) is a new, enteric-coated, porcine-derived pancreatic enzyme product (PEP) developed for the treatment of cystic fibrosis (CF) patients with malabsorption associated with exocrine pancreatic insufficiency (EPI). Unlike currently marketed PEPs, EUR-1008 contains the label-claimed lipase content. Safety and efficacy were assessed in younger (< 7 years) and older (≥ 7 years) CF patients with EPI. Methods Two multicenter studies were conducted: a randomized, double-blind, placebo-controlled, crossover trial in patients ≥ 7 years of age ( N = 34) and a supplemental, open-label study in children < 7 years of age ( N = 19). Use of any medications altering gastric pH/motility was prohibited during the studies. Outcome measures in the randomized trial included changes in the coefficient of fat absorption (CFA), coefficient of nitrogen absorption (CNA), and signs/symptoms of malabsorption for EUR-1008 vs. placebo. Outcome measures in the supplemental study included safety and response (defined as no steatorrhea and no overt signs/symptoms of malabsorption) to EUR-1008 vs. previous enzyme treatment. Results In the randomized trial, EUR-1008 treatment compared to placebo resulted in a significantly higher mean CFA (88.3% vs. 62.8%, respectively) and CNA (87.2% vs. 65.7%, respectively) (both p < 0.001) and reduced the incidence of malabsorption signs and symptoms in 32 evaluable patients. In the supplemental study, 11 of 19 patients met the criteria for responder with EUR-1008 at the end of the study vs. 10 of 19 patients at screening (previous PEP), and improvements in clinical symptoms were reported with EUR-1008 treatment. EUR-1008 was safe and well tolerated, and no serious drug-related AEs were reported in either study. Conclusions EUR-1008 was safe, well tolerated, and effective in CF patients of all ages with EPI-associated malabsorption in two clinical trials. Treatment led to clinically and statistically significant improvements in CFA and CNA in the randomized study, and control of malabsorption and clinical symptoms in both studies.

First FDA-approved pancrelipase product may mark new era for providers, patients

FDA’s recent approval of a reformulated version of Solvay Pharmaceutical Inc.’s delayed-release pancrelipase product, Creon, gives pharmacists who are active in the cystic fibrosis community something new—a pancreatic enzyme product that has passed regulatory muster. Solvay expects the new Creon formulation to be available later this year. The product is indicated for the treatment of children and adults with exocrine pancreatic insufficiency caused by cystic fibrosis or other conditions. The delayed-release oral formulation is designed to release lipase, protease, and amylase in the small intestine instead of the acidic environment of the stomach, which degrades pancreatic enzymes, according to FDA. Only one other pancrelipase product has ever gained FDA approval—Organon’s Cotazym, an immediate-release pancrelipase product that was approved by FDA in 1996 but is not currently marketed, according to the agency. Pancreatic enzyme products have been available in the United States since before the 1938 passage of the Food, Drug, and Cosmetic Act. FDA in 2004 declared pancreatic enzyme products new drugs that required formal agency approval. The agency has given manufacturers until April 2010 to obtain marketing approval of their pancrelipase products.

M1283 Enzyme Delivery Into the Duodenum from a Novel Pancreatic Enzyme Product (Eur-1008) in Chronic Pancreatitis Patients with Exocrine Pancreatic Insufficiency

M1283 Enzyme Delivery Into the Duodenum from a Novel Pancreatic Enzyme Product (Eur-1008) in Chronic Pancreatitis Patients with Exocrine Pancreatic Insufficiency

T1886 Zentase, a Novel Pancreatic Enzyme Product (Pep), Is Effective in Mild, Moderate, and Severe Exocrine Pancreatic Insufficiency (Epi)

T1886 Zentase, a Novel Pancreatic Enzyme Product (Pep), Is Effective in Mild, Moderate, and Severe Exocrine Pancreatic Insufficiency (Epi)

Study of a novel pancreatic enzyme replacement therapy in pancreatic insufficient subjects with cystic fibrosis

We studied a novel pancreatic enzyme product, ALTU-135, a proprietary formulation of microbially derived lipase, protease, and amylase, to determine its efficacy and safety in treatment of pancreatic insufficiency (PI) in patients with cystic fibrosis (CF). Ambulatory subjects with CF-PI (n = 117) had baseline coefficient of fat and nitrogen absorption (CFA and CNA, respectively) determined in an inpatient setting while not receiving pancreatic enzyme replacement therapy. Subjects were then randomized to treatment with ALTU-135 containing 5000 (low), 25,000 (mid), or 100,000 (highest) units of lipase (1:1:0.15 of lipase:protease:amylase) for 28 days. After 14 days, CFA and CNA were re-measured. The primary outcomes were change from baseline in CFA and CNA between treatments. Treatment CFA was significantly greater in the mid and highest dose groups compared with that in the low dose group (P = .0229 and P =.0041, respectively); findings were similar for CNA. Subjects with baseline CFA < or = 40% and > 40% in the 2 higher dose groups had a mean increase of 31 and 8 percentage points in CFA, respectively (P < .0001). ALTU-135 was efficacious during the 1-month study period at the dose of 25,000 units of lipase, 25,000 units of protease, and 3750 units of amylase.

Safety and Preliminary Clinical Activity of a Novel Pancreatic Enzyme Preparation in Pancreatic Insufficient Cystic Fibrosis Patients

Currently available pancreatic enzyme products are crude porcine products with few data available regarding their efficacy, safety, and manufacture. We conducted a phase 1 study of a novel pancreatic enzyme product, TheraCLEC-Total (TCT), a proprietary formulation of microbial-derived lipase, protease, and amylase, to determine its safety and preliminary efficacy in cystic fibrosis. We conducted an open-label, dose-ranging study in 23 subjects diagnosed with pancreatic insufficiency with cystic fibrosis. The subjects received TCT containing lipase dose of 100, 500, 1000, 2500, or 5000 USP U/kg per meal with each meal or snack for 3 days. The clinical and laboratory parameters and adverse events (AEs) were monitored. There were no serious AEs. Most AEs were mild, although gastrointestinal complaints were common. TCT increased the coefficient of fat and nitrogen absorption in all groups except in the low-dose group. At the other dosing levels, the mean coefficient of fat and nitrogen absorption increases were 19.1% +/- 24.9% and 17.8% +/- 13.6%, respectively, whereas the mean stool weight decreased by 517 +/- 362 g. TCT was well tolerated in this short-term exposure study. The preliminary efficacy data demonstrate lipase and protease activity with little difference seen with lipase doses greater than 500 USP U/kg per meal. These data support a larger randomized phase 2 trial.

Regulatory Status of Pancreatic Enzyme Preparations

Hendeles and colleagues¹report on three patients, each of whom took the same defective pancreatic enzyme product and each of whom obtained an unsatisfactory result. The product consisted of capsules of pancrelipase, US Pharmacopeia (USP) formulated into enteric-coated spheres. The product was sold under various names, but all brands were manufactured by and were labeled as having been manufactured by Anabolic, Inc of Irvine, Calif. Information regarding the defective product, including reports of testing conducted by the independent laboratory (Pharmichem Testing Services) and by a competitor, had been received at the Food and Drug Administration (FDA) by May 1989. The FDA's inspection of the firm revealed that there was no validation for the enteric coating process. Testing conducted by the firm confirmed that the enteric coating was ineffective. All lots were either subpotent or superpotent for one or more active ingredients. On June 14,1989, the manufacturer voluntarily instituted a