Currently Enrolling Trials
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 specifically indicated for the treatment of adult men with Peyronie’s disease with a palpable plaque and curvature deformity of at least 30 degrees at the start of therapy.
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.
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
Adverse effects associated with the use of Xiaflex for Peyronie's disease may include, but are not limited to, the following:
- Penile hematoma
- Penile swelling
- Penile pain
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 three times per cord at approximately four-week intervals.
For the treatment of adult men with Peyronie’s disease with a palpable plaque and curvature deformity of at least 30 degrees at the start of therapy, Xiaflex is supplied as a powder for reconstitution into a solution for intralesional injection. The recommended treatment is a follows: Inject 0.58 mg Xiaflex into the target plaque once on each of two days, one to three days apart, according to the injection procedure. For each plaque causing the curvature deformity, up to four treatment cycles may be administered. Each treatment cycle may be repeated at approximately six-week intervals.
Clinical Trial Results
The FDA approval of Xiaflex was based on two randomized, double-blind, placebo-controlled, multicentered trials in 374 adults with Dupuytren’s contracture (Studies 1 and 2). The cord affecting the selected primary joint received up to three 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 four months and instructed to perform a series of finger flexion and extension exercises each day. The primary end point 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 three injections). A greater proportion of Xiaflex-treated patients compared to placebo-treated patients achieved the primary end point. Following the first injection, the proportion of patients who achieved a contracture reduction of the primary joint to 0° to 5° was 39 percent and 1 percent in Study 1 and 27 percent and 5 percent 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 percent and 7 percent in Study I and 44 percent and 5 percent in Study 2 in the Xiaflex and placebo groups, respectively.
The FDA approval of Xiaflex for Peyronie's disease was based on two randomized, placebo-controlled trials in 832 adult males with Peyronie's disease (Studies 1 and 2). All subjects had a penile curvature deformity of at least 30 degrees in the stable phase of Peyronie's disease. The subjects received up to four treatment cycles of Xiaflex or placebo (weeks 0, 6, 12 18) and were followed for weeks 24 through 52. In each treatment cycle, two injections of Xiaflex or placebo were administered one to three days apart. Treatment cycles were repeated at approximately six-week intervals for up to three additional times, for a maximum of eight injection procedures. A penile modeling procedure was performed at the study site one to three days after the second injection of the cycle. Up to four total modeling procedures were performed. The coprimary end points were the percentage change from baseline to Week 52 in penile curvature deformity and the change from baseline to Week 52 in the Bother domain score of the PDQ. Study 1: baseline mean curvaturein the Xiaflex arm was 48.8 degrees and 49.0 degrees in the placebo arm. After treatment the Xiaflex arm had a -35.0 percent change, while the placebo arm had a -17.8 percent change (p< 0.01). Study 2: baseline mean curvature in the Xiaflex arm was 51.3 percent and 49.6 percent in the placebo arm. After treatment the Xiaflex arm had a -33.2 percent change while the placebo arm had a -21.8 percent change (p< 0.01). Xiaflex significantly reduced patient-reported bother associated with Peyronie’s disease compared with placebo (p<0.05).