Mechanism of Action

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.

Results of in vitro studies suggest that the collagenases (AUX-I and AUX-II) worked synergistically to provide hydrolyzing activity towards collagen. However, there are no clinical data regarding the relative contributions of the individual collagenases (AUX-I or AUX-II) to the efficacy of XIAFLEX in the treatment of Dupuytren's contracture.

Pharmacokinetics

Following administration of a single XIAFLEX dose of 0.58 mg into a Dupuytren's cord in 20 patients, no quantifiable levels of XIAFLEX (AUX-I or AUX-II) were detected in plasma up to 30 days post injection.

Clinical Studies

The efficacy of 0.58 mg of XIAFLEX was evaluated in two randomized, double-blind, placebo-controlled, multi-centered trials in 374 adult patients with Dupuytren's contracture (Studies 1 and 2). At study entry, patients must have had: (1) a finger flexion contracture with a palpable cord of at least one finger (other than the thumb) of 20° to 100° in a metacarpophalangeal (MP) joint or 20° to 80° in a proximal interphalangeal (PIP) joint and (2) a positive "table top test" defined as the inability to simultaneously place the affected finger(s) and palm flat against a table top. Patients could not have received a surgical treatment (e.g., fasciectomy, fasciotomy) on the selected primary joint within 90 days before the first injection of study medication and patients could not have received anticoagulation medication (except for up to 150 mg of aspirin per day) within 7 days before the first injection of study medication.

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.

See Table 3 for the baseline disease characteristics of patients with Dupuytren's contracture in Studies 1 and 2.

Table 3. Baseline Disease Characteristics of Patients with Dupuvtren's Contracture

In Studies 1 and 2, 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 (see Table 4).

Table 4. Percentage of Patients Who Achieved Reduction in Contracture of the Primary Joint to 0° to 5° After Up to 3 Injections in Studies 1 and 2^a

The proportion of patients who achieved a contracture reduction of the primary joint to 0° to 5° after the first injection was 39% and 1% in Study 1 and 27% and 5% in Study 2 in the XIAPLEX and placebo groups respectively.

XIAFLEX-treated patients, compared to placebo-treated patients, showed a greater increase from baseline in the range of motion of MP and PIP joints (see Table 5).

Table 5. Mean Increase in Range of Motion from Baseline in Degrees After Up to 3 Injections in Studies 1 and 2^a

Last reviewed on RxList: 3/13/2012
This monograph has been modified to include the generic and brand name in many instances.