Auxilium Pharmaceuticals, Inc. (NASDAQ: AUXL), a specialty biopharmaceutical company, today announced positive data for collagenase clostridium histolyticum or CCH which is being developed for the potential treatment, if approved by the U.S. Food and Drug Administration ("FDA"), of adult patients with adhesive capsulitis ("AC"), commonly known as Frozen Shoulder syndrome ("FSS"). FSS is a common, prolonged, painful condition of the shoulder in which increased capsular collagen thickening and subsequent capsular contraction in the shoulder joint is thought to cause a loss of range of motion in the shoulder. The condition is believed to affect approximately two to five percent of the general adult population and the full duration of the disease can last from approximately 1 year to up to 3.5 years. The majority of cases are currently managed conservatively with prolonged physical therapy and occasionally with steroid injections. It is estimated that approximately 300,000 cases of FSS are diagnosed annually and approximately 10% are treated with an invasive intervention (surgery or manipulation under anesthesia) on an annual basis.
"Positive top-line data from our phase IIa Frozen Shoulder Syndrome clinical trial represent another very encouraging development milestone for Auxilium as we advance a fourth potential indication of CCH, further diversifying our evolving pipeline," explained Adrian Adams , Chief Executive Officer and President of Auxilium. "We believe Frozen Shoulder syndrome represents a condition with few optimal treatment strategies and no approved therapies. Innovative approaches such as CCH may, if approved by the FDA, allow affected patients quicker relief from limits in range of motion and associated pain."
The phase IIa study was an open-label, controlled dose-ranging study designed to assess the safety and efficacy of CCH for the treatment of Stage 2 unilateral idiopathic FSS in comparison to an exercise-only control group. The study involved 50 adult men and women at 11 sites throughout the U.S. Four cohorts of 10 patients each received up to three ultrasound-guided extraarticular injections of varying doses of CCH (ranging from 0.29 mg to 0.58 mg in three different volumes; 0.5, 1.0, or 2.0 mL), separated by a minimum of 21 days. All patients were instructed to perform home shoulder exercises. The fifth cohort of ten patients received no CCH injections and only performed home shoulder exercises. The study's primary endpoint was the change (in degrees) from baseline to the day 92 follow-up in active forward flexion in the affected shoulder compared to the exercise-only cohort. Safety assessments were made during all study visits and immunogenicity testing was performed at screening and day 92.
Both the 0.58mg(1mL) and 0.58mg(2mL) dosing arms showed positive, statistically significant improvement from baseline in forward flexion vs. the exercise-only group. The 0.58mg(1mL) dosing arm also showed statistically significant improvement from baseline in shoulder abduction vs. the exercise-only group. Positive trends with improvement in degrees were also seen in other active range of motion ("AROM") assessments vs. the exercise-only group. Twenty-nine study patients (72.5%) received three CCH injections with 5 subjects receiving two injections and 6 subjects receiving one injection only.
AROM Assessment Results from Phase IIa FSS Study
Patients were also assessed using the American Shoulder and Elbow Surgeons ("ASES") Scale for function and pain. Both the 0.58 mg(1mL) and 0.58 mg(2mL) cohort demonstrated statistically significant improvement in pain and function over baseline scores vs. the exercise-only group (p<0.05).
"We are very pleased with study results demonstrating a dose response with CCH, significant improvement in multiple range of motion measurements and a well-tolerated safety profile in this phase IIa study," said Dr. James Tursi , Chief Medical Officer of Auxilium. "We look forward to advancing the clinical development of CCH in Frozen Shoulder syndrome and are currently assessing options to determine the safest and optimal path forward in development."
Treatment-related adverse events with CCH were mostly localized bruising, injection site pain and swelling, hematoma, and musculoskeletal pain. All such events resolved without intervention, and are consistent with XIAFLEX/CCH use in other approved and potential indications. No subjects discontinued the study due to an adverse event. A shoulder MRI was performed on all patients at screening and day 92. Screening MRIs were performed to exclude the presence of other clinically significant conditions such as concomitant rotator cuff injury. Day 92 MRI evaluations indicated there were no rotator cuff injuries. There were no drug-related serious adverse events reported.
Auxilium Pharmaceuticals, Inc.