“This study suggests that eculizumab, by inhibiting the activation of terminal complement, could be effective in preventing acute AMR, which is a severe and life-threatening complication in sensitized patients undergoing kidney transplantation,” said Martin Mackay, Ph.D., Executive Vice President and Global Head of R&D at Alexion. “We are encouraged by the data presented today from this deceased-donor study, and also continue to enroll patients in our multi-national living-donor transplant trial in patients at elevated risk of AMR.”
Eculizumab is approved in over 40 countries as a treatment for patients with paroxysmal nocturnal hemoglobinuria (PNH) and in the United States, European Union and other countries for patients with atypical hemolytic uremic syndrome (aHUS). PNH and aHUS are both debilitating and life-threatening ultra-rare disorders caused by chronic, uncontrolled complement activation. Eculizumab is not approved for the prevention of AMR in any country and was used in the reported study on an investigational basis.
About the Study
Nine-week preliminary results were presented from an open-label, single-arm, multicenter Phase 2 trial in which 47 sensitized recipients of kidneys from deceased donors were treated with eculizumab. The mean age of the study participants was 50 years (range: 29-70). 1The study’s primary efficacy composite endpoint was post-transplantation treatment failure rate at Week 9, defined by biopsy-proven AMR, graft loss, patient death, and/or loss to follow-up. Preliminary results presented today are for the primary endpoint modified with utilization of local laboratory data (the pre-specified primary endpoint uses central lab data). At Week 9, 5 patients (10.6%; 95% confidence interval [CI]: 3.5%, 23.1%) were considered treatment failures, of which 3 (6.4%) had acute AMR. The three most common serious adverse events from Weeks 1 to 11 were complications of the transplanted kidney (12.8%), transplant rejection (8.5%), and acute renal failure (8.5%). One patient (2%) in the study died due to a post-operative myocardial infarction deemed not related to eculizumab. 1 About Acute Antibody-Mediated Rejection (AMR) Acute antibody-mediated rejection (AMR) is a severe and potentially life-threatening condition that can lead to severe kidney allograft damage resulting in rapid loss of function and possible loss of the transplanted kidney. Patients who are sensitized (have high levels of donor-specific-antibodies or DSAs) are at high risk for developing acute AMR, may have difficulty finding a viable donor organ, and therefore may never become eligible for transplantation. The development of acute AMR is believed to be primarily a result of uncontrolled complement activation caused by DSAs, which in turn frequently results in allograft damage and dysfunction, potential graft loss, and/or shortened graft survival.