ZENTASE, A NOVEL PANCREATIC ENZYME PRODUCT (PEP), IS SAFE AND EFFECTIVE IN MILD, MODERATE, AND AGGRESSIVE EXOCRINE PANCREATIC INSUFFICIENCY (EPI)

Abstract

Background: PEP therapy helps prevent maldigestion and malabsorption in patients with EPI. This phase III, randomized, double-blind, placebo-controlled, multicenter trial evaluated the efficacy and safety of Zentase (EUR-1008), a novel, zero-overfill, highly-stable formulation of porcine-derived pancreatic enzymes, in cystic fibrosis (CF) patients with EPI. Methods: Patients had confirmed CF and EPI, age ≥7 years, fecal elastase < 100 ng/g good nutritional status and weight ≤ 70 kg. Patients with a coefficient of fat absorption (CFA) > 80% were included. No drugs affecting gastric pH or motility were allowed. After open-label dose titration, patients were randomized to one week of Zentase or placebo. Following another open-label normalization, patients were crossed over to the alternative treatment arm. The primary endpoint was change in CFA following oral administration of Zentase vs. placebo. Secondary endpoints included change in coefficient of nitrogen absorption (CNA), cholesterol, fat soluble vitamins, and malabsorption signs and symptoms. Safety was also evaluated. Results: Thirty-four patients were enrolled (mean age 15.4 years); 32 were evaluated. Zentase treatment was associated with significant increases in both CFA and CNA vs. placebo (P < 0.001), improved vitamin K status and improvement in malabsorption signs and symptoms, including a statistically significant reduction in stool frequency and fewer soft/watery stools. Zentase treatment improved signs and symptoms of malabsorption regardless of EPI severity, including in patients with CFA values > 80% on placebo treatment. A positive correlation was observed between Zentase dose and response, particularly in patients with abnormal stool at baseline. Zentase was safe and well-tolerated, with no unexpected or significant differences in the frequency or type of AEs between Zentase and placebo. Two serious AEs were considered unrelated to the study drug and both resolved. Conclusion: In this Phase III study, Zentase, a novel PEP, was safe, well tolerated and effective in the treatment of EPI, with clinically and statistically significant improvements in CFA, CNA, and malabsorption signs and symptoms in the absence of any concomitant treatment affecting gastrointestinal motility and pH. The therapeutic benefit of Zentase was seen in patients with mild EPI (CFA values >80% on placebo), as well as in patients with moderate and aggressive disease.