Home » Drug Information » FDA Approved Drugs » 2010
Medical Areas: Musculoskeletal
View By:YearCompanyConditionsTherapeutic AreasDrug Names
Xiaflex (collagenase clostridium histolyticum)
The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Company: Auxilium Pharmaceuticals
Approval Status: Approved February 2010
Treatment Area: Dupuytren’s contracture
Xiaflex contains purified collagenase clostridium histolyticum. When injected directly into a Dupuytren’s cord, it enzymatically disrupts collagen. As a result of collagen disruption, contracture may be reduced and range of motion may be improved.
Xiaflex is specifically indicated for the treatment of adult patients with Dupuytren’s contracture with a palpable cord.
Xiaflex is supplied as a lyophilized powder for reconstitution with the provided diluent. It is injected directly into the Dupuytren’s cord. The recommended initial dose is 0.58 mg per injection into a palpable cord with a contracture of a metacarpophalangeal (MP) joint or a proximal interphalangeal (PIP) joint. Approximately 24 hours after injection, a finger extension procedure should be performed if a contracture persists to facilitate cord disruption. Four weeks after the Xiaflex injection and finger extension procedure, if a MP or PIP contracture remains, the cord may be re-injected with a single dose of 0.58 mg of Xiaflex and the finger extension procedure may be repeated (approximately 24 hours after injection). Injections and finger extension procedures may be administered up to 3 times per cord at approximately 4-week intervals.
The FDA approval of Xiaflex was based on two randomized, double-blind, placebo-controlled, multi-centered trials in 374 adults with Dupuytren’s contracture (Studies 1 and 2). The cord affecting the selected primary joint received up to 3 injections of 0.58 mg of Xiaflex or placebo on Days 0, 30, and 60. About 24 hours after each injection of study medication, if needed, the investigator manipulated (extended) the treated finger in an attempt to facilitate rupture of the cord (finger extension procedure). Following manipulation, patients were fitted with a splint, instructed to wear the splint at bedtime for up to 4 months, and instructed to perform a series of finger flexion and extension exercises each day. The primary endpoint was to evaluate the proportion of patients who achieved a reduction in contracture of the selected primary joint (MP or PIP) to within 0° to 5° of normal, 30 days after the last injection of that joint on Days 30, 60, or 90 (after up to 3 injections). A greater proportion of Xiaflex-treated patients compared to placebo-treated patients achieved the primary endpoint. Following the first injection, the proportion of patients who achieved a contracture reduction of the primary joint to 0° to 5° was 39% and 1% in Study 1 and 27% and 5% in Study 2 in the Xiaflex and placebo groups respectively. Following up to three injections, the percentage of patients who achieved reduction in contracture of all joints (MP and PIP) to 0° to 5° was 64% and 7% in Study I and 44% and 5% in Study 2 in the Xiaflex and placebo groups respectively.
Adverse events associated with Xiaflex may include, but are not limited to, the following:
- Edema (peripheral, mostly swelling of the injected hand)
- Injection site reaction
- Injection site hemorrhage
- Pain in the treated extremity
Mechanism of Action
Xiaflex contains purified collagenase clostridium histolyticum, consisting of two microbial collagenases in a defined mass ratio, Collagenase AUX-I and Collagenase AUX-II, which are isolated and purified from the fermentation of Clostridium histolyticum bacteria. Collagenases are proteinases that hydrolyze collagen in its native triple helical conformation under physiological conditions, resulting in lysis of collagen deposits. Injection of Xiaflex into a Dupuytren’s cord, which is comprised mostly of collagen, may result in enzymatic disruption of the cord.
Hurst LC, Badalamente MA, Hentz VR, Hotchkiss RN, Kaplan FT, Meals RA, Smith TM, Rodzvilla J; CORD I Study Group Injectable collagenase clostridium histolyticum for Dupuytren's contracture. The New England Journal of Medicine 2009 Sep 3;361(10):968-79
For additional information regarding Xiaflex or Dupuytren’s contracture, please visit the Xiaflex web page.