— Preliminary Data Show Potential for Effective Prophylaxis Against Early Acute AMR in Deceased-Donor Kidney Transplant Recipients Highly Sensitized to Their Donors —
Acute AMR can lead to severe kidney allograft damage resulting in rapid loss of function and possible loss of the transplanted kidney, which makes AMR a significant clinical barrier to transplantation in sensitized patients.3 Research suggests that uncontrolled activation of complement, triggered by the binding of donor-specific antibodies (DSAs) to their target proteins (antigens) of the donor kidney, may be the primary reason for acute AMR in kidney transplant recipients who are sensitized, or have DSAs, to their donors.3,4 Prophylaxis with a terminal complement inhibitor, such as eculizumab, is thus considered a potential strategy to prevent acute AMR. There are no approved treatments for the prevention of acute AMR.
"Approximately 30% of kidney transplant candidates on waiting lists are sensitized, or have antibodies, to potential donors. Because conventional immunosuppressive therapies are ineffective for the prevention of AMR, sensitized patients often have to wait years for a kidney suitable for transplantation. Thus, AMR has emerged as a significant, long-standing clinical problem in transplantation," said
"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
Eculizumab is approved in over 40 countries as a treatment for patients with paroxysmal nocturnal hemoglobinuria (PNH) and in
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).1
The 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.
While solid organ transplantation is the most effective form of therapy for the treatment of patients with end-stage renal disease (ESRD),5 concern about the consequences of AMR remains a significant obstacle to transplantation, as it results in significant delays for affected patients to access a suitable transplant. Overall, ESRD patients on dialysis have a very high mortality rate since approximately 65% of these patients die within 5 years of commencing dialysis.6 Additionally, approximately one-third of patients on the kidney transplant waiting list are sensitized to their potential donors7 and historically, approximately 30% of this highly sensitized population has developed AMR.2 A therapy that prevents acute AMR is critically important for sensitized patients with ESRD. Currently, there are no approved therapies for the prevention of acute AMR.
About Soliris
Soliris is a first-in-class terminal complement inhibitor developed from the laboratory through regulatory approval and commercialization by Alexion. Soliris is approved in
Soliris also is approved in the US, EU,
Alexion's breakthrough approach in terminal complement inhibition has received the pharmaceutical industry's highest honors: the 2008
More information, including the full prescribing information on Soliris, is available at www.soliris.net.
Important Safety Information
The US product label for Soliris includes a boxed warning: "Life-threatening and fatal meningococcal infections have occurred in patients treated with Soliris. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early. Comply with the most current
In patients with PNH, the most frequently reported adverse events observed with Soliris treatment in clinical studies were headache, nasopharyngitis (runny nose), back pain and nausea. Soliris treatment of patients with PNH should not alter anticoagulant management because the effect of withdrawal of anticoagulant therapy during Soliris treatment has not been established. In patients with aHUS, the most frequently reported adverse events observed with Soliris treatment in clinical studies were hypertension, upper respiratory tract infection, diarrhea, headache, anemia, vomiting, nausea, urinary tract infection, and leukopenia. Please see full prescribing information for Soliris, including boxed WARNING regarding risk of serious meningococcal infection.
About Alexion
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Safe Harbor Statement
This news release contains forward-looking statements, including statements related to anticipated clinical development, regulatory and commercial milestones and potential health and medical benefits of Soliris® (eculizumab) for the prevention of antibody mediated rejection (AMR) in kidney transplant recipients. Forward-looking statements are subject to factors that may cause Alexion's results and plans to differ from those expected, including for example, decisions of regulatory authorities regarding marketing approval or material limitations on the marketing of Soliris for its current or potential new indications, and a variety of other risks set forth from time to time in Alexion's filings with the
1 Glotz D, Legendre C, Manook M, et al. Eculizumab decreases early antibody-mediated rejection in sensitized deceased donor kidney transplant patients. Presented at the 2013
2 LeFaucher C, Loupy A, Hill GS, et al. Preexisting donor-specific HLA antibodies predict outcome in kidney transplantation. J Am Soc Nephrol. 2010;21:1398-1406.
3 Takemoto SK, Zeevi A, Feng S, et al. National conference to assess antibody-mediated rejection in solid organ transplantation. Am J Transplant. 2004;4(7):1033-41.
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5 Russell JD, Beecroft ML, Ludwin D, Churchill DN. The quality of life in renal transplantation—a prospective study. Transplantation 1992;54(4):656-60.
6 Kidney disease statistics for
7 About CPRA for Professionals.
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