Endo International’s attempt to use ultrasound-guided injection of collagenase clostridium histolyticum (CCH) to treat frozen shoulder has come unstuck. The drug, the active ingredient in the approved Xiaflex, failed to beat placebo in a phase 2 clinical trial, driving Endo to reevaluate its plans in the indication.
Xiaflex is already used to treat Dupuytren's contracture, a thickening of tissue in the hand, and Peyronie's disease, a condition that causes the penis to bend when erect. In both indications, the active ingredient is injected directly into the affected tissue, where it helps break down the cord or plaque at the root of the problem.
Like Dupuytren's and Peyronie's, frozen shoulder, known medically as adhesive capsulitis, is caused by the thickening of tissue. The challenge is how to deliver CCH to the targeted tissue enclosing the joint.
Endo identified ultrasound-guided injection, an approach explored in Dupuytren's, as a way to get the active ingredient to the affected tissue. A phase 2 clinical trial put the idea to the test, randomizing 198 participants to receive up to three ultrasound-guided injections of CCH or placebo.
At Day 95, participants in the treatment group performed no better statistically than their peers on placebo on a scale that measures the functional limitations and pain of the shoulder. Endo saw “some improvement” in the scores of patients receiving CCH, but the improvement over placebo was too small for the study to hit its primary endpoint.
"We are disappointed in the study outcome, and based on these data, we will be reevaluating our path forward for CCH for the treatment of adhesive capsulitis of the shoulder. We will continue focusing on our pipeline, including with respect to other potential CCH indications," James Tursi, executive vice president of global R&D at Endo, said in a statement.