CREON (Pancrelipase) Delayed-Release Capsules Significantly Improves Fat Absorption in Children with Cystic Fibrosis, Study in Clinical Therapeutics Reports

Data CONFIRMS safe and effective use of CREON® in pediATRIC PAtients -

MARIETTA, Ga., Feb. 5 /PRNewswire-FirstCall/ -- Solvay Pharmaceuticals, Inc. announced today that Phase IIIb data published in the January issue of Clinical Therapeutics confirm that CREON® (pancrelipase) Delayed-Release Capsules significantly improves a key measure of fat absorption in children aged 7-11 years who have exocrine pancreatic insufficiency (EPI) due to cystic fibrosis (CF), 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.

In this clinical study, children aged 7-11 years with EPI due to CF experienced an improved coefficient of fat absorption (CFA) during treatment with CREON® compared to treatment with placebo. CFA is calculated based on measures of fat ingestion and fat excretion; assessing the CFA of a patient is another way to measure the absorption of fat as a percentage of fat intake in patients being tested for EPI. The mean CFA was greater during treatment with CREON® (82.8%) compared to treatment with placebo (47.4%), which resulted in a significant difference of 35.4% (p < 0.001).

Results were similar for a secondary outcome measure of the study, the coefficient of nitrogen absorption (CNA). CNA was used as a measure to evaluate the absorption of proteins. CNA is calculated based on the amount of nitrogen intake and nitrogen excretion. The mean CNA was greater during treatment with CREON® (80.3%) compared to treatment with placebo (45.0%), which resulted in a significant difference of 35.3% (p < 0.001).

"If not treated properly, EPI can lead to maldigestion and serious malabsorption of key nutrients, which can be life-shortening," said Gavin Graff M.D, Penn State Milton S. Hershey Medical Center, Penn State Medical School. "CREON® was effective in improving CFA and CNA, which should help maintain adequate nutrition and normal growth in young children with EPI due to CF."

Findings from this Phase IIIb study have been submitted to the FDA. CREON® is already FDA-approved and indicated for the treatment of EPI due to CF and other conditions in patients ages zero and above. Solvay Pharmaceuticals is committed to the continued clinical study and development of CREON® as further confirmation of the safety and efficacy of pancreatic enzyme replacement therapy (PERT) for the treatment of children.

The safety and efficacy of PERTs with different formulations of pancrelipase consisting of the same active ingredient as CREON® (lipases, proteases, and amylases) for treatment of children with exocrine pancreatic insufficiency due to cystic fibrosis have been described in the medical literature. There is a history of using different formulations of CREON® to treat pediatric patients with EPI due to CF, which has demonstrated efficacy and safety in those patients through years of clinical experience.

Pediatric Study Details

The short-term, double-blind, randomized, multicenter, placebo-controlled, cross-over study examined the efficacy and safety of CREON® (pancrelipase) Delayed-Release 12,000 lipase unit capsules at a dose of 4,000 lipase units/g of dietary fat intake per day for five days in 16 patients ages 7-11 years with EPI due to CF. EPI was confirmed in all subjects by a CFA of < 70% without pancreatic enzyme supplementation or human fecal elastase < 50 micrograms/gram stool within 12 months prior to start of study.

Upon analysis of the primary efficacy outcome, the mean CFA was greater during treatment with CREON® (82.8%) compared to treatment with placebo (47.4%), which resulted in a significant difference of 35.4% (p < 0.001). Thus, the study met its primary objective and showed a superior efficacy of CREON® over placebo based on the CFA. Secondary outcome measures analyzed included the CNA and clinical symptoms. The mean CNA was greater during treatment with CREON® (80.3%) compared to treatment with placebo (45.0%), which resulted in a significant difference of 35.3% (p < 0.001). Treatment-emergent adverse events (TEAEs), which were predominantly gastrointestinal events, were reported in five patients during treatment with CREON® and nine patients during treatment with placebo. No serious TEAEs were reported.

About Exocrine Pancreatic Insufficiency and Pancreatic Enzyme Replacement Therapies

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

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 CREON® 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 CREON® is not chewed or retained in the mouth to avoid irritation of oral mucosa. Caution should be exercised when prescribing CREON® to patients with gout, renal impairment, or hyperuricemia. There is theoretical risk of viral transmission with all pancreatic enzyme products, including CREON®. 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 CREON®, the incidence of adverse events (regardless of causality) was higher during placebo treatment (71%) than during CREON® treatment (50%). Treatment-emergent adverse events occurring in at least two patients (greater than or equal to 6%) receiving CREON® or placebo were abdominal pain, abdominal pain upper, abnormal feces, cough, dizziness, flatulence, headache, and weight decreased.

CREON® 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 CREON®, 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 CREON®, 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                     Jeannine Pilla
  Solvay Pharmaceuticals, Inc.      Ruder Finn
  (770) 578-5637                    (212) 593-5823
  jessica.riley@solvay.com          pillaj@ruderfinn.com

Source: Solvay Pharmaceuticals, Inc.

CONTACT: Jessica Riley, Solvay Pharmaceuticals, Inc., +1-770-578-5637,
jessica.riley@solvay.com; or Jeannine Pilla, Ruder Finn, +1-212-593-5823,
pillaj@ruderfinn.com

Web Site: http://www.creon.com/

Posted: February 2010

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