Eurand's Zentase Effective In Treating Exocrine Pancreatic Insufficiency

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Results from two phase III studies of Zentase showing a statistically and clinically significant improvement in the absorption of fat, protein and nutrients in patients suffering from Exocrine Pancreatic Insufficiency.

Absorption levels were measured by coefficient of fat (CFA) and coefficient of nitrogen (CNA) absorption, common measurements for malabsorption in EPI patients. In the pivotal study, the mean CFA after Zentase was 88.3 percent and the mean CNA after Zentase was 87.2 percent. Levels under placebo were 62.8 and 65.7 percent respectively (p=0.001). Scientific evidence suggests that to normalize EPI, treatment needs to raise CFA levels to at least 85 percent.

The data were the basis for the recent rolling submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for Zentase as a treatment for EPI. EPI is a potentially lethal disease marked by the deficiency of digestive enzymes normally produced by the pancreas. This deficiency results in poor digestion and reduced absorption of nutrients, which, if left untreated, can lead to malnutrition, impaired growth, weakened immune response, and shortened life expectancy. Treatment with pancreatic enzyme products (PEPs) replaces enzymes lost through the disease. Currently, there are no known alternative therapies to PEPs for EPI.

EPI can occur as a complication of a variety of diseases, including cystic fibrosis, pancreatic cancer, surgery and chronic pancreatitis. There are no reliable statistics on the worldwide incidence of EPI, but in the U.S., it is estimated that more than 200,000 people suffer from EPI.

"Nutritional status, lung function and life expectancy are tightly connected in cystic fibrosis patients. In general, enhancing CFA and CNA levels improves nutrition. Good nutrition improves lung function. And, better lung function improves life expectancy," said James E. Heubi, MD, Director, General Clinical Research Center, Professor of Pediatrics, Cincinnati Children's Hospital Medical Center. "These data suggest that Zentase could provide EPI patients with an effective treatment option that would normalize CFA which could protect lung function and increase life expectancy."

Zentase is a zero-overfill, highly-stable, porcine-derived PEP. If approved by the FDA, it is expected to be available in four dose strengths, including a low-dose formulation for children that can be sprinkled on food.

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"As a company, our goal is to develop products that optimize efficacy and tolerability while meeting patient needs for convenience, which is why we developed Zentase specifically with patients in mind," said Gearoid Faherty, Chief Executive Officer, Eurand. "The data presented in Turkey are an indication that with Zentase, we are well on the way toward meeting that goal."

About the Studies

The two phase III studies were designed to test Zentase in EPI patients presenting with the full range of disease severity. The studies included patients from 1-24 years of age with disease severity including mild, moderate and severe malabsorption. Half of the patients enrolled in the pivotal study had a baseline CFA greater than 65 percent and half had a baseline CFA lower than 65 percent (median CFA levels were 65.8 percent). Patients enrolled in the pivotal study had a wide range of baseline CFA levels with one patient as low as 28.7 percent (very severe disease) and five patients with CFA levels above 80 percent.

The majority of EPI patients in the pivotal study, regardless of disease severity, experienced a clinically significant response to Zentase treatment. Half of these patients had a CFA greater than 90 percent following Zentase treatment and 90 percent of patients had a CFA greater than 79 percent following Zentase treatment. Based on these study findings, Zentase may able to treat all patient types, from those requiring low levels of supplementation to those with severe disease needing high levels of enzyme supplementation.

Pivotal Study Highlights

This randomized, double-blind, placebo-controlled, cross-over study was conducted in 14 CF centers in the US and involved data from 31 patients with EPI. The average age was 15.4 years and the study was evenly split between male and female patients. After open-label dose titration, patients were randomized to receive Zentase or placebo over a week-long period. Following open-label normalization, all patients were crossed over to the alternative treatment arm. A determination of CFA and CNA on a 72-hour sample and under controlled diet in a hospital environment was performed at the end of each randomized treatment arm. No drugs affecting GI motility or pH (eg, PPIs or H2 blockers) were allowed under Zentase treatment.

-- Direct Dose Response on Improving EPI Symptoms. Increasing the Zentase dose displayed a direct correlation on improving EPI symptoms including stool consistency and symptom scores including measures of pain, bloating, gas and oil visibility.

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