Axcan Pharma Inc. has submitted the complete New Drug Application (NDA) for Ultrase in the treatment of Exocrine Pancreatic Insufficiency (EPI), with the US Food and Drug Administration (FDA). The FDA had already granted Ultrase a Fast Track designation, which allows promising new drugs and biological products that treat serious, life-threatening or severely debilitating diseases to proceed more rapidly through the regulatory process.
"We are excited that the results of our clinical studies and CMC work have led to the submission of the Ultrase NDA. This submission exemplifies our commitment to providing valuable therapeutic options for significant unmet needs in the pancreatic insufficiency segment of the gastrointestinal market, as we have been doing for over 15 years," said Frank Verwiel, M.D., president and chief executive officer of Axcan. "As previously mentioned, we expect to be amongst the first companies to have approved pancreatic enzyme products on the US market, which should allow us to remain a leader within this market," he added.
In April 2004, the FDA formally notified manufacturers of pancreatic insufficiency products that these drugs must receive approval before April 2008 in order to remain on the market. Ultrase is a pancreatic enzyme replacement therapy that does not require overfill, and will therefore be filled at 100 per cent of label claim. The formulation of Ultrase for which the NDA was submitted has been designed to meet FDA guidelines for pancreatic enzyme replacement products.
The NDA is based on a clinical study program that included Phase III, multi-centre, double-blinded, placebo-controlled crossover trials. In the two initial Phase III studies previously disclosed (Aliment Pharmacol. Ther. 2004; 20: 1365-1371), patients with pancreatic insufficiency associated with cystic fibrosis received either Ultrase MT12, or Ultrase MT20, or a placebo. Results of this study demonstrated excellent effects on fat absorption with minimal adverse events. Baseline fat absorption levels without enzyme supplementation (placebo) were 46.7% and 58.7% respectively in the Ultrase MT12 and Ultrase MT20 study groups. Mean fat absorption increased to 79.4% and 87.3% respectively for the Ultrase MT12 and Ultrase MT20 study groups.
The company also recently completed an additional phase III clinical study, also included in the NDA, with the currently marketed Ultrase MT20 formulation. This multi-centre, randomized, double-blind, crossover study was designed to compare the efficacy and safety of Ultrase MT20 to placebo in the correction of steatorrhea in patients with cystic fibrosis.
Results of this study also demonstrated excellent effects on the primary efficacy parameter, i.e. fat absorption, with minimal adverse events. "A highly significant clinical and statistical difference in mean fat absorption between Ultrase MT20 and placebo was observed, in line with the results previously observed in the published studies on Ultrase and clearly above the absorption level thought to be required for enzyme supplementation for cystic fibrosis patients," commented Dr. Michael Konstan, Lead Investigator for the study (Rainbow Babies and Children's Hospital, Cleveland, OH), which was conducted with the assistance of the Cystic Fibrosis Therapeutics Development Network. The Company plans to have Dr. Konstan disclose detailed results of the study in the coming months, in the appropriate scientific forum.
In addition, the Ultrase NDA includes an intestinal perfusion study aimed at measuring the bioactivity of lipase at the site of action, as requested by the FDA. Results of this analysis confirmed that ultrase MT20 effectively delivers lipase to the site of action. It is expected that the Principal Investigator, Dr. Philip Toskes (University of Florida, Gainesville, FL), will publish and present this component of the NDA in the coming months, in the appropriate scientific forum.
Axcan is a leading multinational specialty pharmaceutical company focused on gastroenterology. The company develops and markets a broad line of prescription products to treat a range of gastrointestinal diseases and disorders such as inflammatory bowel disease, irritable bowel syndrome, cholestatic liver diseases and complications related to pancreatic insufficiency.