RECOTHROM topical hemostat exhibits low rate of anti-product antibody formation

Feb 2 2010

ZymoGenetics, Inc. (NASDAQ:ZGEN), today announced the publication of pooled safety and immunogenicity observations from eight clinical trials of RECOTHROM in the February issue of the Journal of the American College of Surgeons. The authors concluded that RECOTHROM is a well-tolerated topical hemostatic agent in numerous surgical settings and has a low rate of anti-product antibody formation. In the pooled data from all trials, less than one percent of treated patients developed product-specific antibodies. None of the antibodies neutralized native coagulation proteins.

“These pooled safety data are significant, as they provide a robust clinical trial data set for a topical hemostat”

“These pooled safety data are significant, as they provide a robust clinical trial data set for a topical hemostat,” said Fred Weaver, MD, FACS, a study author and Professor of Surgery at USC CardioVascular Thoracic Institute, USC University Hospital, Keck School of Medicine, University of Southern California, Los Angeles, CA. “The adverse events observed were consistent with those expected in the surgical populations studied, and immune response to RECOTHROM was consistently low, with no development of antibodies that neutralized native human thrombin.”

The eight clinical trials (one Phase 1 trial, five Phase 2 trials, one randomized, double-blind Phase 3 trial, and one open-label Phase 3b trial) included 583 patients, ranging in age from 12 through 89 years, with no hypersensitivity to thrombin or other coagulation factors. Surgical procedures included spinal (33%), hepatic resection (14%), peripheral arterial bypass (23%), arteriovenous graft formation for hemodialysis access (18%), and skin graft after burn wound excision (12%).

In each of the studies, RECOTHROM was administered during a single surgical procedure; adverse events as well as clinical hematology and coagulation laboratory parameters were monitored through post-operative (post-op) day 29. Patients were tested for anti-RECOTHROM antibodies at baseline and at the post-op day 29 assessment.

Adverse events reported for ≥ 10% of RECOTHROM-treated patients included incision site pain, procedural pain, nausea, constipation, pyrexia, anemia, insomnia, vomiting, and pruritis. These adverse events are commonly reported in patients undergoing surgery, and variation in the observed incidence of these events across surgery types was consistent with the specific type of procedure and surgical patient population.

After treatment with RECOTHROM, less than one percent of patients for whom complete immunogenicity observations were available developed anti-RECOTHROM antibodies (5 of 552 patients or 0.9%). The antibodies identified did not neutralize the activity of native human thrombin.