Collagenase clostridium histolyticum (Xiaflex) and collagenase clostridium histolyticum-aaes (Qwo) each contains two forms of microbial collagenase (collagenase AUX-I and collagenase AUX-II), which are isolated and purified from the fermentation of Clostridium histolyticum bacteria.
Collagenase clostridium histolyticum is marketed under brand names Xiaflex and Qwo, each of which serves distinct populations. Xiaflex’s approved indications include Peyronie's disease and Dupuytren's contracture, and Qwo is approved for the treatment of moderate-severe buttocks cellulite in adult women.
Xiaflex is composed of proteinases that hydrolyze collagen, leading to enzymatic disruption of contracted Dupuytren cord or Peyronie plaque, both of which are composed primarily of collagen, whereas Qwo enzymatically targets the fibrous connective tissue tethering the skin to the underlying fascia; disruption of these fibrous septae diminishes the "dimpling" effect and leads to improved cellulite appearance.
Dupuytren's contracture is a disease that causes a deformity of the palmar and digital fascia of the hand. Abnormal deposition of collagen initially causes nodules in the palm of the hand, which may lead to the formation of cords. With the progression of the disease, the cords gradually contract, leading to deformities of the fingers. Damage to a joint is typically painless but is associated with significant functional impairment. The exact etiology of Dupuytren's contracture is unknown, but some risk factors have been identified, including alcohol, smoking, diabetes, epilepsy, thyroid disorders, and trauma.
Peyronie's disease is an acquired penile condition caused by fibrosis of the tunica albuginea that consists of three connective tissue layers: an outer layer of mesothelium apposed to the basal lamina (tunica vaginalis), a middle layer of dense fibrous tissue, and an inner layer of loose connective tissue (tunica vascularis) with nerve fibers and abundant blood and lymphatic vessels. Peyronie's disease may cause pain, deformity, erectile dysfunction, and/or distress. Usually repeated minor trauma to the penis initiates a cascade involving extravascular protein deposition, fibrin trapping, and overexpression of cytokines, leading to collagen changes characteristic of the condition. Males around 50 years of age are most commonly affected. Most individuals with Peyronie's disease will have pain resolved over time without intervention, but curvature deformities are less likely to resolve without treatment.
Cellulite involves fibrous connective cords that tether the skin to the underlying muscle, with the fat lying between. As fat cells accumulate, they push up against the skin, while the long, tough cords pull down. This creates an uneven surface or dimpling.
On December 6, 2013, the FDA approved Collagenase clostridium histolyticum (Xiaflex) for the treatment of Peyronie's disease in male adult individuals. The efficacy of collagenase clostridium histolyticum (Xiaflex) was evaluated in two randomized, double-blind, placebo-controlled, multi-centered trials in 832 adult males with Peyronie's disease. At study entry, individuals had penile curvature deformity of at least 30 degrees in the stable phase of Peyronie's disease. Individuals were excluded if they had a ventral curvature deformity, an isolated hourglass deformity, or a calcified plaque that could have interfered with the injection technique. At baseline, penile pain was either not present or was mild in most individuals. Individuals were given up to four treatment cycles of Xiaflex or placebo. In each treatment cycle, two injections of collagenase clostridium histolyticum (Xiaflex) or two injections of placebo were administered one to three days apart. The primary endpoints were the percent change from baseline to week 52 in penile curvature deformity and the change from baseline to week 52 in the Bother domain score. The Bother domain score is a composite of the following individual-reported items: concern about erection pain, erection appearance, and the impact of Peyronie's disease on intercourse and on the frequency of intercourse. Collagenase clostridium histolyticum (Xiaflex) treatment significantly improved penile curvature deformity in individuals with Peyronie's disease compared with placebo. Collagenase clostridium histolyticum (Xiaflex) also significantly reduced individual-reported bother associated with Peyronie's disease compared with placebo. Serious adverse events were three cases of corporeal rupture requiring surgical repair and three cases of a penile hematoma.
On February 3, 2010, the FDA approved Collagenase clostridium histolyticum (Xiaflex) for the treatment of Dupuytren's contracture in adult individuals. The safety and efficacy of collagenase clostridium histolyticum (Xiaflex) in Dupuytren's contracture was evaluated in two randomized, double-blind, placebo-controlled, multi-centered trials in 374 adult individuals with Dupuytren's contracture. At study entry, individuals must have had 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 a positive “table top test" defined as the inability to simultaneously place the affected finger(s) and palm flat against a tabletop. The cord affecting the selected primary joint received up to 3 injections of 0.58 mg of collagenase clostridium histolyticum (Xiaflex) or placebo on days 0, 30, and 60. About 24 hours after each injection of study medication, if needed, the investigator manipulated the treated finger in an attempt to facilitate the rupture of the cord. The primary endpoint was the proportion of individuals who achieved a reduction in a contracture of the selected primary joint (MP or PIP) to within 0° to 5° of normal 30 days after the last injection. Both studies showed a statistically significant reduction in contracture in the Xiaflex group compared to the placebo group.
Cosmetic procedures are those provided to improve an individual's physical appearance, from which no significant improvement in physiologic function can be expected. Emotional and/or psychological improvement alone does not constitute an improvement in physiologic function.
Collagenase clostridium histolyticum-aaes (Qwo) is a prescription medication used to treat moderate-severe buttocks cellulite in adult women via subcutaneous injection. Specifically, Qwo enzymatically targets the fibrous connective tissue tethering the skin to the underlying fascia; disruption of these fibrous septae diminishes the "dimpling" effect and leads to improved cellulite appearance. Although Qwo is the same pharmaceutical substance as Xiaflex, it is not indicated for the treatment of Peyronie's disease or Dupuytren's contracture; it is approved solely for cosmetic usage.
OFF-LABEL INDICATIONS There may be additional indications contained in the Policy section of this document due to the evaluation of criteria highlighted in the Company's off-label policy, and/or review of clinical guidelines issues by leading professional organizations and government entities.