Enzyme Product Approved for Rare Hand Disorder

Kate Traynor

BETHESDA, MD 03 February 2010—FDA and Auxilium Pharmaceuticals announced the licensing of collagenase clostridium histolyticum, or Xiaflex for injection, for the treatment of Dupuytren's contracture in adults.

According to FDA, Xiaflex is the first product cleared by the agency with labeling for the treatment of the rare disease, which affects the hands and can prevent the normal use of the fingers.

The FDA-approved labeling (PDF) for collagenase clostridium histolyticum states that it is indicated for patients who have a palpable tissue cord in the hand.

According to the labeling, Xiaflex consists of two purified microbial collagenases. When injected into a Dupuytren's cord, which is made mostly of collagen, enzymatic disruption may occur and result in improved hand movement.

The labeling warns that tendon rupture can occur if the product comes into contact with collagen-containing structures other than the Dupuytren's cord. In clinical studies, 0.3% of 1082 patients treated with Xiaflex had a flexor tendon rupture of the treated finger within 7 days of the injection.

In some cases, the labeling warns, patients may need surgery to repair tendon or ligament damage resulting from the use of the enzyme product.

Injection-site reactions, including swelling, bruising, bleeding, and pain are "likely" to occur during treatment, the labeling states.

Xiaflex is intended for administration by clinicians with experience performing injections in the hands. A risk evaluation and mitigation strategy (REMS) for the product requires physicians to attest that they have completed a training program before obtaining Xiaflex, according to Auxilium. The REMS also includes a medication guide for patients.

Xiaflex will be available in single-use, glass vials containing 0.9 mg of collagenase clostridium histolyticum as a sterile, lyophilized powder. Included in each package is a single-use, glass vial of diluent consisting of 3 mL of 0.3 mg/mL calcium chloride dihydrate in 0.9% sodium chloride.

The unreconstituted product should be refrigerated at 4–8 degrees C. After reconstitution, the solution can be stored up to one hour at room temperature or refrigerated for four hours before use.

The recommended dosage of Xiaflex is 0.58 mg injected into a palpable Dupuytren’s cord with a contracture of a metacarpophalangeal joint or a proximal interphalangeal joint. If contracture persists after 24 hours, a finger extension procedure should be performed.

The injection-and-extension procedure can be repeated up to three times per cord approximately once every four weeks, the labeling states. Only one cord should be treated at a time.

Auxilium plans to begin shipping Xiaflex to distributors in early March and officially launch the product late in the month.