Collagenase: Preclinical Evaluation and Clinical Trials in the USA and Australia
Prior to US Food and Drug Administration approval of injectable collagenase, the standard of care was surgical fasciectomy, which in many cases can result in suboptimal treatment outcomes and a high recurrence rate. Injectable collagenase Clostridium histolyticum represents a novel, nonsurgical approach to the treatment of Dupuytren contracture. Early, proof-of-principle, basic science studies, using a rat tail tendon model and surgically removed Dupuytren cords, yielded favorable results. Clinical studies in humans were then conducted, where the primary end point was reduction in contracture to within 0–5° of normal extension (0°) after the last injection. Phase 2 studies which confirmed the optimal dose of collagenase as 10,000 units (0.58 mg) showed injectable collagenase reduced contractures in metacarpophalangeal (MP) and proximal interphalangeal (PIP) joints to within 0–5° of normal after the last injection in a substantial number of joints and was well tolerated. Clinical results from phase 3 studies confirmed the efficacy and safety of injectable collagenase as a viable nonsurgical intervention for the treatment of patients with Dupuytren contracture, translating the observations made in the laboratory into the clinical setting.