Dupuytren’s disease (cord, pit, or nodule) is estimated to be present in 3% to 6% of the adult Caucasian population.1 A Dupuytren’s cord is characterized by excessive collagen deposition in the palmar fascia of the hand resulting in a ropelike cord, which limits finger movement and causes a permanent flexion deformity. The current standard of care is surgical removal of the cord. However, as surgery can be associated with major complications, alternative therapeutics should be considered.2
XIAFLEX (Auxilium Pharmaceuticals Inc., Malvern, Pa.), is a non-surgical injectable therapy that is the only FDA-approved treatment of Dupuytren’s contracture. Pharmacologic activity of XIAFLEX involves the enzymatic disruption of the pathologic Dupuytren’s cord. XIAFLEX is comprised of two collagenases and results of in vitro studies suggest that they work synergistically to provide hydrolyzing activity towards collagen.
XIAFLEX 0.58 mg should be injected into the palpable Dupuytren’s cord affecting the metacarpophalangeal or proximal interphalangeal joint. Approximately 24 hours after injection, a finger extension procedure is performed to facilitate cord disruption, if the contracture persists. Subsequent injections and finger extension procedures may be administered up to three times per cord at approximately four-week intervals.
Thirteen clinical studies have been conducted in subjects with Dupuytren’s contracture in the US, Europe, and Australia (1,082 subjects, 2,630 XIAFLEX injections). Results from two Phase 3 double-blind, placebo-controlled studies demonstrated that XIAFLEX (0.58 mg) was superior to placebo with respect to the percentage of subjects who achieved reduction in contracture of their primary joint to ?5° after the last injection (p < 0.001).2,3
Subjects treated with XIAFLEX had a greater reduction in baseline contracture, a greater increase in range of motion (a surrogate of functionality), and a shorter time to achieve clinical success of primary joint compared to placebo. Most treatment-related adverse events—AEs occurring in ?25% include edema peripheral, contusion, injection site hemorrhage/reaction and pain in extremity—were mild or moderate in intensity and resolved without intervention. Injection of XIAFLEX into collagen-containing structures, such as tendons or ligaments of the hand, may result in damage to those structures and possible permanent injury, such as tendon rupture or ligament damage.
Auxilium Pharmaceuticals acquired certain global development rights from BioSpecifics Technologies Corp. in June 2004. In late 2008, Auxilium formed a development partnership with Pfizer for Dupuytren’s contracture and Peyronie’s disease in 46 EU and Eurasian countries. Overall, the evidence suggests that XIAFLEX provides a safe and effective treatment for patients with Dupuytren’s contracture and an alternative to surgical correction.
References
1. Hurst LC, et al. Injectable Collagenase Clostridium Histolyticum for Dupuytren’s Contracture. NJEM. 2009;361:968-979.
2. Rayan GM. Dupuytren disease: Anatomy, pathology, presentation, and treatment. J Bone Joint Surg Am. 2007 Jan;89(1):189-98.
3. Data on file, Auxilium Pharmaceuticals, Inc.
A shortened form of this article was published in Drug Discovery & Development magazine: Vol. 13, No. 3, April 2010, p. 11.
Filed Under: Drug Discovery
