Review of Selected NMEs 2014

Jack DeRuiter, PhD; Pamela L. Holston, RPh, BS, BA; Taylor Joseph DeRuiter, PharmD Candidate

Disclosures

US Pharmacist. 2014;39:HS-2-HS-15. 

In This Article

Collagenase Clostridium Histolyticum (Xiaflex, Auxilium Pharmaceuticals)

Indication and Clinical Profile7

Xiaflex is the first FDA-approved nonsurgical treatment for curvature of the penis (Peyronie disease; PD). In PD, scar tissue develops under the skin of the penis, causing an abnormal bend during erection and resulting in bothersome symptoms, especially during intercourse. Xiaflex was approved in 2010 for the treatment of Dupuytren contracture, a progressive hand disease that can affect a person's ability to straighten and properly use his or her fingers. Xiaflex is specifically indicated for the treatment of adults with PD with a palpable plaque and curvature deformity ≥30 degrees at therapy initiation.

FDA approval of Xiaflex for PD was based on two controlled trials in 832 adults (studies 1 and 2) with penile curvature deformity of ≥30 degrees in the stable phase of disease. Subjects received up to four treatment cycles of Xiaflex or placebo (weeks 0, 6, 12, 18) and were followed for weeks 24 to 52. In each treatment cycle, two injections of Xiaflex or placebo were administered 1 to 3 days apart, and treatment cycles were repeated at approximately 6-week intervals up to three additional times, for a maximum of eight injection procedures. A penile modeling procedure was performed 1 to 3 days after the second injection of the cycle. The coprimary endpoints were the percentage change from baseline to week 52 in penile curvature deformity and the change from baseline to week 52. Upon completion of study 1, the Xiaflex arm had a –35.0% change, whereas the placebo arm had a –17.8% change. In study 2, the Xiaflex arm had a –33.2% change, whereas the placebo arm had a –21.8% change. Xiaflex also significantly reduced patient-reported bothersome symptoms associated with PD, compared with placebo.

Pharmacology and Pharmacokinetics7

Xiaflex is an injectable formulation of purified collagenase, an enzyme that causes collagen to degrade within the connective tissue. Injection of Xiaflex into a Peyronie collagen plaque appears to result in enzymatic disruption of the plaque. Following disruption of the plaque, penile curvature deformity and bothersome symptoms caused by PD are reduced.

Intralesional administration of Xiaflex results in minimal systemic absorption and distribution. In clinical trials, patients receiving two injections 24 hours apart had only minimal plasma levels, and this effect was short-lived.

Adverse Reactions and Drug Interactions7

The most common adverse reactions associated with the use of Xiaflex for PD were injection-site reactions, including penile hematoma, swelling, and pain. Other less common adverse reactions included lymphadenopathy, itching, edema, and local bruising and bleeding. Allergic reactions were observed in <1% of patients. The drug carries a boxed warning for corporeal rupture (penile fracture) and other serious penile injury, since these events were reported in a small percentage of Xiaflex-treated patients in clinical studies. As a result, for PD treatment, Xiaflex is available only through a restricted Risk Evaluation and Mitigation Strategy (REMS) program. The REMS program requires that participating healthcare professionals and facilities be certified by enrolling and completing training in the administration of Xiaflex for PD. Xiaflex is contraindicated in patients with Peyronie plaques that involve the penile urethra and in those with a history of severe allergic reaction to collagenase used in other therapeutic applications.

No drug-interaction studies have been conducted because the drug does not appear to reach systemic circulation. It is proposed that drugs that interfere with matrix metalloproteinases, such as tetracyclines, anthracyclines, quinolones, and anthraquinone derivatives, could reduce the efficacy of collagenases, but no clinical evidence of such interactions has been reported.

Dosage and Administration7

Xiaflex is supplied in single-use vials containing 0.9 mg of active drug as a sterile powder for reconstitution in a solution for intralesional injection. The recommended treatment involves injection of 0.58 mg Xiaflex into the target plaque once on each of two days, 1 to 3 days apart, according to the injection procedure. For each plaque causing the curvature deformity, up to four treatment cycles may be administered. Treatment cycles may be repeated at approximately 6-week intervals.

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