Press Release: Eurand Announces Positive Phase III Clinical Study Results

Eurand Announces Positive Phase III Clinical Study Results MILAN, Italy and DAYTON, Ohio, April 4 -- Eurand, a global specialty pharmaceutical company, today unveiled data from two phase III clinical trials on its lead product candidate, Zentase(TM), formerly EUR-1008, for the treatment of Exocrine Pancreatic Insufficiency (EPI). The US Food and Drug Administration (FDA) granted fast track status for Zentase for the treatment of EPI. The company intends to file for FDA approval during the second quarter of 2007 for this potentially first-in-class pancreatic enzyme replacement therapy. Zentase is a zero-overfill, highly-stable, porcine-derived pancreatic enzyme replacement therapy used to treat EPI and was designed to meet FDA guidelines for pancreatic enzyme replacement products(1). According to the FDA, no currently marketed pancreatic enzyme product (PEP) has been shown to demonstrate consistent enzyme bioactivity that results in predictable safety and effectiveness(2). Many of the current enzyme products contain overfill to compensate for product instability during shelf life, which can lead to variability in dosing. As a highly-stable product, Zentase does not require overfill. Currently, there are no FDA approved PEPs for the treatment of EPI on the market in the US. "We are excited to present the results of our phase III studies supporting Zentase for the full spectrum of cystic fibrosis patients suffering from EPI, including those needing limited supplementation to those with very aggressive enzyme deficiency," said Gearoid Faherty, Eurand Chairman and CEO. Zentase met all primary and secondary endpoints in two phase III clinical trials. The studies were designed to determine whether the product candidate could alleviate serious malabsorption associated with EPI in both a pediatric (younger than 7 years) and an older patient population. Study results showed a clinically and statistically significant increase in the coefficient of fat absorption (CFA) in patients treated with Zentase. The mean percentage of CFA in patients receiving Zentase was 88.3 percent versus 62.8 percent in patients receiving placebo (p<0.001). Treatment guidelines suggest that the CFA should be at least 85 percent in cystic fibrosis (CF) patients(3). "The protocols for these trials were reviewed by the FDA and developed in collaboration with the Cystic Fibrosis Foundation (CFF). We want to thank the CFF for their support," added Faherty. Phase III Pivotal Study Results This randomized, double-blind, placebo-controlled, cross-over study evaluated CF patients with EPI aged seven years and older. Patients treated with Zentase showed a statistically significant increase in the coefficient of fat absorption and coefficient of nitrogen absorption (CNA) as compared to those receiving a placebo. They also had fewer symptoms associated with impaired absorption such as bloating, flatulence, pain and evidence of fat in stools. Moreover, in all study patients, regardless of starting levels while taking placebo, Zentase returned CFA and CNA absorption levels to ranges considered normal in healthy patients. We believe this suggests Zentase can provide the level of enzyme supplementation required by cystic fibrosis patients with different levels of EPI. "I believe the results of this successful trial demonstrated the efficacy and safety of Zentase," said James E. Heubi, MD, Professor and Associate Chair for Clinical Research of Pediatrics at Children's Hospital Medical Center in Cincinnati, OH. "During the study, the level of fat absorption achieved with Zentase was very high and close to levels seen in healthy patients, even without the use of proton pump inhibitors (PPIs). This high fat absorption, without relying on PPIs could significantly reduce the number of pills patients take each day." Phase III Pediatric Supportive Study Results This open label study in CF patients under the age of seven involved a seven-day dose stabilization period followed by a seven-day treatment period. The study evaluated the percentage of "responders," or those patients without excess fat in stools and without signs and symptoms of malabsorption after one and two weeks of treatment. Secondary endpoints included weight change, nutritional status, stool frequency and consistency, incidences of bloating, pain and flatulence as well as physician and parent or guardian judgment of clinical symptoms improvement. In the study, malabsorption symptoms were significantly lower at the end of treatment than at screening, consistent with control of malabsorption symptoms with Zentase in the pivotal phase III trial. EPI and Cystic Fibrosis EPI is a deficiency of digestive enzymes normally produced by the pancreas. The deficiency leads to malnutrition, impaired growth in children and shortened life expectancy. EPI is commonly associated with cystic fibrosis and chronic pancreatitis. Cystic Fibrosis affects about 30,000 individuals in the US and 100,000 worldwide. Approximately 90 percent of these individuals suffer from EPI. Treatment with PEPs helps replace enzymes lost through this disease. Other than enzyme replacement, Eurand is not aware of any other alternative therapy for EPI. Zentase Zentase is a zero-overfill, highly-stable, porcine-derived pancreatic enzyme replacement therapy designed to treat EPI, a deficiency of digestive enzymes normally produced by the pancreas. Zentase closely mimics the enzyme profile of normal human pancreatic secretions. Formulated with eight key enzymes and other co-enzymes and cofactors required for proper digestion, Zentase is highly stable and requires no product overfill. The product is being developed in multiple strengths as well as a pediatric formulation, which can be sprinkled on food for easier administration to young children. The full results of the two phase III trials will be published in peer reviewed journals and presented at upcoming medical meetings in the United States and Europe. About Eurand Eurand is a specialty pharmaceutical company that develops enhanced pharmaceutical and biopharmaceutical products based on its proprietary drug formulation technologies. Eurand has had four products approved by the FDA since 2000 and has a pipeline of product candidates in development for itself and its partners. Eurand's technology platforms include bioavailability enhancement of poorly soluble drugs, customized release, taste-making/fast- dissolving formulations and drug conjugation. Eurand is a global company with research, development and manufacturing facilities in Milan, Italy, Dayton, Ohio, USA, Trieste, Italy and Paris, France. For more information, visit Eurand's website at This release, and oral statements made with respect to information contained in this release, constitutes forward-looking statements. Such forward-looking statements include those which express plan, anticipation, intent, contingency, goals, targets or future development and/or otherwise are not statements of historical fact. These statements are based upon management's current expectations and are subject to risks and uncertainties, known and unknown, which could cause actual results and developments to differ materially from those expressed or implied in such statements. (1) Guidance for Industry Exocrine Pancreatic Insufficiency Drug Products -Submitting NDAs U.S. Department of Health and Human Services, Food and Drug Administration (FDA), Center for Drug Evaluation and Research (CDER), April 2006 (2) Federal Register/ Vol. 69 No. 82. April 28, 2004 (3) Littlewood, James M., and Susan P. Wolfe. "Control of Malabsorption in Cystic Fibrosis." Paediatric Drugs (2000; 2 : 205-22)