MARIETTA, Ga., Oct. 9 Solvay Pharmaceuticals, Inc. announced today that Phase III data published in the Journal of Cystic Fibrosis showed that CREONŽ (pancrelipase) Delayed-Release Capsules, the most prescribed pancreatic enzyme replacement therapy (PERT) in the United States, significantly improves a key measure of fat absorption in patients with CF who suffer from exocrine pancreatic insufficiency (EPI). EPI is a condition resulting from a deficiency in the production and/or secretion of pancreatic enzymes that are necessary to digest nutrients in food and, if untreated, can lead to poor growth, poor weight gain and failure to thrive in children with CF.
According to the study results, patients with CF and confirmed EPI had an improved coefficient of fat absorption (CFA) during treatment with CREONŽ compared to treatment with placebo. CFA is calculated based on measures of fat ingestion and fat excretion; assessing the CFA of a patient is a way to measure the absorption of fat as a percentage of fat intake in patients being tested for EPI. The trial reached statistical significance on its primary endpoint, which was CFA.
"These study results demonstrate that CREONŽ is effective in decreasing the maldigestion and malabsorption associated with pancreatic insufficiency in patients with cystic fibrosis," said Bruce C. Trapnell, MD, Professor of Medicine and Pediatrics at the University of Cincinnati and Cincinnati Children's Hospital Medical Center. "Patients enrolled in this study had poor fat absorption without treatment, which is commonly associated with uncomfortable gastrointestinal symptoms and severe malnutrition. In addition to the impressive increase in fat absorption demonstrated in these individuals, the secondary outcomes of the study have important implications for those involved in the care of these patients."
CREONŽ was approved by the Food and Drug Administration (FDA) with an indication to treat EPI due to CF or other conditions based on the results of this clinical study. As the first FDA-approved PERT, CREONŽ was also the first product in the class to provide a Medication Guide with important dosing information, including instructions for administration to infants and toddlers, which is consistent with the CF Foundation Consensus Conference Guidelines.
The double-blind, randomized, placebo-controlled two-arm, crossover study examined the efficacy and safety of CREONŽ (Pancrelipase) Delayed-Release 24,000 lipase unit capsules in subjects aged 12 years or older with EPI due to CF. EPI was confirmed in all subjects by a CFA of <70% without pancreatic enzyme supplementation or fecal elastase <50 micrograms/gram stool within 12 months prior to start of study. Upon analysis of the primary efficacy results, the mean CFA was greater during treatment with CREONŽ (88.6%) compared with placebo (49.6%), and the difference was statistically significant (p < 0.001). Thus, the study met its primary objective and showed superior efficacy of CREONŽ over placebo based on CFA. Adverse clinical symptoms including stool frequency, abdominal pain, stool consistency and flatulence, occurred less frequently during treatment with CREONŽ, compared to treatment with placebo. Additionally, abdominal pain and flatulence were less severe and stool consistency was less watery during treatment with CREONŽ.
About Exocrine Pancreatic Insufficiency and Pancreatic Enzyme Replacement Therapy
Exocrine pancreatic insufficiency (EPI) is a condition resulting from a deficiency in the production and/or secretion of pancreatic enzymes that are necessary to digest nutrients in food. The safety and efficacy of prior formulations of pancrelipase in pediatric patients with EPI due to CF have been described in the medical literature. Prior formulations of pancrelipase have also demonstrated clinical efficacy in those patients through years of clinical experience. PERTs work in patients with EPI by delivering pancreatic enzymes to the small intestine to help break down fats, proteins and carbohydrates in food, thereby acting as a replacement for digestive enzymes physiologically secreted by the pancreas. EPI can occur as a complication of a variety of diseases or conditions, including CF, pancreatic cancer, gastrointestinal surgery and chronic pancreatitis. Statistics show that more than 80% of CF patients have EPI, which usually develops during the first year of life.
The original products in the pancreatic enzyme drug class pre-date modern FDA regulatory requirements. Over the past two decades, products in this class have been allowed to be marketed as prescription drugs without formal NDA approval. In 2004, the FDA required manufacturers to submit New Drug Applications (NDAs) for all pancreatic enzyme replacement therapies in order to remain on the market. By April 2010, all pancreatic enzyme replacement therapies are required to have approved NDAs and must be manufactured under the new guidelines.
Important Safety Information about FDA-Approved CREONŽ
Warnings and precautions include fibrosing colonopathy, a rare, serious adverse reaction that has been described in association with high-dose use of pancreatic enzyme replacement therapy in the treatment of cystic fibrosis patients. Caution should be exercised when doses of CREONŽ exceed 2,500 lipase units/kg of body weight per meal (or greater than 10,000 lipase units/kg of body weight per day). Care should be taken to ensure that CREONŽ is not chewed or retained in the mouth to avoid irritation of oral mucosa. Caution should be exercised when prescribing CREONŽ to patients with gout, renal impairment, or hyperuricemia. There is theoretical risk of viral transmission with all pancreatic enzyme products, including CREONŽ. Caution should be exercised when administering pancrelipase to a patient with a known allergy to proteins of porcine origin.
In the clinical study used to demonstrate the efficacy and safety of FDA-approved CREONŽ, the incidence of adverse events (regardless of causality) was higher during placebo treatment (71%) than during CREONŽ treatment (50%). Treatment-emergent adverse events occurring in at least two patients (greater than or equal to 6%) receiving CREONŽ or placebo were abdominal pain, abdominal pain upper, abnormal feces, cough, dizziness, flatulence, headache, and weight decreased.
CREONŽ has been approved with a Risk Evaluation and Mitigation Strategy (REMS) to ensure that the benefits of the drug outweigh its risks. As part of the REMS, a Medication Guide with important dosing and safety information applicable to this class of products, including CREONŽ, is provided for patients and caregivers, with an emphasis on understanding the risk of fibrosing colonopathy as well as the importance of not over- or under-dosing. The FDA requires that the Medication Guide be handed out with every prescription for the drug dispensed.
For full safety and Prescribing Information about the FDA-approved formulation of CREONŽ, visit www.CREON.com.
Solvay Pharmaceuticals, Inc., of Marietta, Georgia, is the U.S. subsidiary of Solvay Pharmaceuticals. For more information, visit www.solvaypharmaceuticals-us.com.
Solvay Pharmaceuticals is a research driven group of companies that constitutes the global pharmaceutical business of the Solvay Group. These companies seek to fulfill carefully selected, unmet medical needs in the therapeutic areas of neuroscience, cardiometabolic, influenza vaccines, gastroenterology and men's and women's health. Its 2008 sales were EUR 2.7 billion and it employs more than 9,000 people worldwide. For more information, visit www.solvaypharmaceuticals.com.
Solvay is an international Chemicals and Pharmaceuticals Group with headquarters in Brussels. It employs some 28,300 people in 50 countries. In 2008, its sales amounted to EUR 9.5 billion generated by its three activity sectors: Chemicals, Plastics and Pharmaceuticals. Solvay (NYSE-Euronext: SOLB.BE - Bloomberg: SOLB.BB - Reuters: SOLBt.BR) is listed on NYSE-Euronext at Brussels. Details are available at www.solvay.com.
CONTACT: Jessica Riley Aaron Estrada Solvay Pharmaceuticals, Inc. Ruder Finn (770) 578-5637 (212) 715-1568 [email protected] [email protected]
SOURCE Solvay Pharmaceuticals, Inc.