New Medical Therapies™

Dupuytren's Disease

August 6, 2012

Auxilium Pharmaceuticals released top-line results from a phase IIIb trial of Xiaflex for the treatment of Dupuytren’s contracture. This open-label study enrolled 60 adult patients with at least two Dupuytren’s contractures caused by palpable cords. Subjects received two concurrent injections of 0.58mg of Xiaflex per affected hand. At Day 30, 60% of all joints, 76% of metacarpophalangeal and 33% proximal interphalangeal joints achieved clinical success (defined as joint correction to 0 to 5 degrees) following this single injection. The response rates are numerically higher than the response rates seen after the first single injection in the double-blind placebo controlled phase III studies. The drug was well tolerated. The most frequent adverse events were bruising, pain and swelling at the treatment site, and were comparable to the previous trials. Based on these data, Auxilium expects to begin a larger study with Xiaflex in the third quarter 2012.

June 9, 2008

Auxilium released positive results from two phase III trials of Xiaflex for the treatment of Dupuytren's contracture. These double-blind, randomized, placebo-controlled studies were dubbed CORD (Collagenase Option for Reducing Dupuytren's) I and II. The primary endpoint for both studies was to determine if Xiaflex can reduce the contracture angle in metacarpophalangeal (MP) or proximal interphalangeal (PIP) joints to greater than or equal to 5 degrees of normal. CORD I enrolled 306 subjects in the US. The primary endpoint was met, with 64% of the primary joints treated with Xiaflex achieving this goal compared to 6.8% of the primary joints treated with placebo (p < 0.001). On average, the subjects who achieved the primary endpoint received 1.5 Xiaflex injections. All secondary endpoints were reached as well, including the difference between the pre- and post-treatment contracture angles and whether there was at least a 50% reduction in contracture compared to baseline. The average percent improvement in contracture from baseline was 79.3% for primary joints treated with Xiaflex, compared to placebo, where the average percent improvement 8.6% (p < 0.001). Of the subjects in the Xiaflex arm, 84.7% achieved at least a 50% reduction in their primary joint contracture from baseline, compared with 11.7% of subjects treated with placebo (p < 0.001). CORD II enrolled 66 subjects in Australia. The primary endpoint was met, with 44.4% of the primary joints treated with Xiaflex achieving greater than or equal to 5 degrees of normal contracture, compared to only 4.8% of the primary joints treated with placebo (p < 0.001). On average, the subjects who achieved the primary endpoint received 1.5 Xiaflex injections. All secondary endpoints were reached as well. The average percent improvement in contracture from baseline was 70.5% for primary joints treated with Xiaflex compared to a 13.6% average percent improvement for primary joints treated with placebo (p < 0.001). A less than or equal to 50% reduction from baseline in the affected joint's contracture was achieved in 77.8% of subjects of all primary joints treated with Xiaflex compared to 14.3% of subjects for joints treated with placebo (p < 0.001). Two additional phase III trials are currently underway and Auxilium plans to file a BLA with the FDA in early 2009.

March 11, 2002

Phase II trial results indicate that treatment with BioSpecifics Technologies Cordase (collagenase) improves extension in subjects with Dupuytrens disease. The controlled, double-blind, dose-response trial included 80 subjects (64 male, 16 female) with a mean baseline fixed flexion deformity of 49 degrees. Subjects received either 2,500, 5,000 or 10,000 units of collagenase or placebo. Of the 16 subjects treated in the MP joint who received 10,000 units of collagenase, 13 returned to normal extension (0-5 degrees) at one-month post treatment. Five of seven subjects treated in the PIP joint who received 10,000 units of collagenase also returned to normal extension after one month.