Benzinga | Sep 30, 2021 11:10AM EDT

Endo Presents New Investigational Collagenase Clostridium Histolyticum (Cch) Survey Data At American Society For Surgery Of The Hand (Assh) Annual Meeting

Survey data indicated a high level of consensus among expert hand surgeons for using CCH for the treatment of metacarpophalangeal (MP) and/or joint contractures of varying severity and MP and/or interphalangeal thumb contractures; data also achieved consensus for using CCH for treating proximal interphalangeal (PIP) joint contractures of varying severities

* Consensus-based findings among expert hand surgeons point to wide-ranging application of CCH for the treatment of DD for patients with varying degrees of disease severity and functional impairment

Endo International plc (NASDAQ:ENDP) today announced results from the first two rounds of Delphi research exploring the expert positions of hand surgeons on the appropriate treatment of Dupuytren's disease (DD) with collagenase clostridium histolyticum (CCH) in patients with varying degrees of disease severity and functional impairment. The data are being presented on an e-poster at the American Society for Surgery of the Hand (ASSH) Annual Meeting in San Francisco, September 30--October 2. The poster is viewable here.

Dupuytren's disease is a heterogenous fibroproliferative condition of the palmar fascia characterized by the development of fascial nodules and cords that may result in digital contracture affecting hand function.1,2 XIAFLEX(r) (collagenase clostridium histolyticum) is a nonsurgical treatment option composed of two purified collagenases that work to break down collagen when injected into fibrous tissue.3

"There are multiple nonsurgical and surgical options available to hand surgeons to effectively treat Dupuytren's disease, but right now, we don't have guidelines to support shared decision-making," said Gary M. Pess, MD, presenting author and a hand and upper extremity surgeon practicing in New Jersey. "These results demonstrate agreement among participating experienced hand surgeons that CCH may be an appropriate choice for patients with varying degrees of Dupuytren's contracture."

About the Report

Researchers used a modified Delphi method employing three successive online survey rounds to capture the clinical expertise of panelists and determine if consensus could be reached regarding the use of CCH for the treatment of DD.

In Round 1, 22 real-world case scenarios were used to determine the panelists' recommendations for using CCH to treat metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joint contractures involving a single finger or 2 fingers, with varying degrees of contracture and clinical severity. Each scenario presented a distinct contracture(s) with a series of statements to evaluate the impact of patient- or disease-related features (ie, age, recurrence, risk of anesthesia, diathesis, poor-quality skin, post-fasciectomy scarring) on the clinical decision to use CCH. Appropriate use of CCH for the treatment of thumb contractures and in patients who are on blood thinners other than aspirin also were explored.

Researchers captured responses using a 5-point Likert scale ("strongly agree," "agree," "deficient information," "disagree," and "strongly disagree"). Level of agreement for each statement was determined, with a consensus threshold of ?66.7% for agreement ("strongly agree" and "agree") or disagreement ("strongly disagree" and "disagree").

Of the 33 hand surgeons who were invited based on their expertise in DD, 22 agreed to participate in the survey, 20 of whom completed Round 1 of the survey; 19 completed Round 2. Overall, 80% had practiced medicine for at least 15 years and all had completed a fellowship in hand surgery. Ninety percent were added qualification [CAQ]-certified hand surgeons.

Consensus data from Rounds 1 and 2 indicated a high level of consensus for using CCH for the treatment of MP joint contractures of varying severity and in patients with MP and/or interphalangeal thumb contractures. Additional contextual data in Round 2 helped achieve consensus for using CCH for treating PIP joint contractures of varying severities. Statements not achieving consensus are being explored in Round 3. Consensus-based findings among expert hand surgeons point to wide-ranging application of CCH for the treatment of DD for patients with varying degrees of disease severity and functional impairment.

IMPORTANT SAFETY INFORMATION FOR XIAFLEX(r)

* XIAFLEX is contraindicated in patients with a history of hypersensitivity to XIAFLEX or to collagenase used in any other therapeutic application or application method

* In the controlled and uncontrolled portions of clinical trials in Dupuytren's contracture, flexor tendon ruptures occurred after XIAFLEX injection. Injection of XIAFLEX into collagen-containing structures such as tendons or ligaments of the hand may result in damage to those structures and possible permanent injury such as tendon rupture or ligament damage. Therefore, XIAFLEX should be injected only into the collagen cord with a metacarpophalangeal (MP) or proximal interphalangeal (PIP) joint contracture, and care should be taken to avoid injecting into tendons, nerves, blood vessels, or other collagen-containing structures of the hand. When injecting a cord affecting a PIP joint of the fifth finger, the needle insertion should not be more than 2 to 3 mm in depth and avoid injecting more than 4 mm distal to the palmar digital crease

* Other XIAFLEX-associated serious local adverse reactions in the controlled and uncontrolled portions of the clinical studies included pulley rupture, ligament injury, complex regional pain syndrome (CRPS), sensory abnormality of the hand, and skin laceration (tear). In a historically controlled post-marketing trial, the incidence of skin laceration (22%) was higher for subjects treated with two concurrent injections of XIAFLEX compared with subjects treated with up to three single injections in the placebo-controlled premarketing trials (9%). Postmarketing cases of skin laceration requiring skin graft after finger extension procedures and local skin and soft-tissue necrosis, some requiring skin grafting, or other surgical interventions including finger amputation have been reported. Signs or symptoms that may reflect serious injury to the injected finger/hand should be promptly evaluated because surgical intervention may be required

* In the controlled portions of the clinical trials in Dupuytren's contracture, a greater proportion of XIAFLEX-treated patients (15%) compared to placebo-treated patients (1%) had mild allergic reactions (pruritus) after up to 3 injections. The incidence of XIAFLEX-associated pruritus increased after more XIAFLEX injections in patients with Dupuytren's contracture

* Because XIAFLEX contains foreign proteins, severe allergic reactions to XIAFLEX can occur. Anaphylaxis was reported in a post-marketing clinical trial in one patient who had previous exposure to XIAFLEX for the treatment of Dupuytren's contracture. Healthcare providers should be prepared to address severe allergic reactions following XIAFLEX injections

* In the XIAFLEX trials in Dupuytren's contracture, 70% and 38% ofXIAFLEX-treated patients developed an ecchymosis/contusion or an injection site hemorrhage, respectively. Patients with abnormal coagulation (except for patients taking low-dose aspirin, eg, up to 150 mg per day) were excluded from participating in these studies. Therefore, the efficacy and safety of XIAFLEX in patients receiving anticoagulant medications (other than low-dose aspirin, eg, up to 150 mg per day) within 7 days prior to XIAFLEX administration is not known. In addition, it is recommended to avoid use of XIAFLEX in patients with coagulation disorders, including patients receiving concomitant anticoagulants (except for low-dose aspirin)

* In the XIAFLEX clinical trials for Dupuytren's contracture, the most common adverse reactions reported in ?25% of patients treated with XIAFLEX and at an incidence greater than placebo were edema peripheral (eg, swelling of the injected hand), contusion, injection site hemorrhage, injection site reaction, and pain in the injected extremity