Worldwide, there is an unmet medical need for a highly innovative therapy for patients at high risk of developing DGF, as there are no approved treatments to prevent DGF after kidney transplantation.6 In most cases DGF results from ischemia/reperfusion injury (IRI). IRI is due to multiple processes that occur following the restoration of blood flow to an area that had previously experienced deficient blood flow.7 Uncontrolled complement activation following IRI is believed to play a major role in the development of DGF.8-11
"Delayed graft function is a serious and significant complication to successful kidney transplantation, which can be life-threatening due to the risk of losing the transplanted organ," said
Soliris is currently approved in nearly 50 countries for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) and in nearly 40 countries for the treatment of atypical hemolytic uremic syndrome (aHUS), two debilitating, ultra-rare and life-threatening disorders caused by chronic uncontrolled complement activation. Soliris is not approved in any country for the prevention of DGF after kidney transplantation.
About the DGF Study
The trial is a multinational, double-blind, placebo-controlled study with the primary objective of assessing the efficacy and safety of a two-dose regimen of eculizumab to prevent DGF in adult recipients of deceased-donor kidney transplants who are at increased risk of DGF. The primary endpoint is the incidence of DGF, defined as the requirement for dialysis for any reason in the first seven days post-treatment. Secondary endpoints include safety and tolerability as well as additional efficacy outcome measures. Patient enrollment and dosing have commenced in this trial. Recruitment is open to adults with dialysis-dependent renal failure who are to receive a first kidney transplant from a deceased donor at high-risk of developing DGF.2 More information about the trial is available at www.clinicaltrials.gov under the identifier NCT02145182.
In
About Delayed Graft Function (DGF)
DGF is an early and serious complication of organ transplantation that is characterized by the failure of a transplanted organ to function immediately following transplantation. When DGF occurs in the setting of kidney transplantation, the patient requires dialysis after the transplantation procedure.3-5 Most often, DGF results from organ injury caused by severe inflammation and complement activation associated with the normal processes of removal and transplantation of the donor organ.3-5,12 DGF has a substantial negative impact on graft function, both in the short and long term, which can result in premature graft loss, prolonged hospitalization or patient death.13,14 In addition, as donor organs are in short supply, reducing the risk of DGF for organs that are at higher risk of developing DGF may allow more donor organs to be transplanted. With specific regard to kidney transplantation, 15-20 percent of donor kidneys are reportedly never used and thus discarded each year in the U.S. and
Currently, there are no approved therapies to prevent DGF after kidney transplantation.
About Soliris® (eculizumab)
Soliris is a first-in-class terminal complement inhibitor developed from the laboratory through regulatory approval and commercialization by Alexion. Soliris is approved in the U.S. (2007),
More information including the full U.S. prescribing information on Soliris is available at: http://soliris.net/sites/default/files/assets/soliris_pi.pdf.
Important Safety Information
The U.S. 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 [see Warnings and Precautions (5.1)]. 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 headache, diarrhea, hypertension, upper respiratory infection, abdominal pain, vomiting, nasopharyngitis, anemia, cough, peripheral edema, nausea, urinary tract infections, pyrexia. Soliris is not indicated for the treatment of patients with Shiga-toxin E. coli-related hemolytic uremic syndrome (STEC-HUS). Please see full prescribing information for Soliris, including BOXED WARNING regarding risk of serious meningococcal infection.
About Alexion
Alexion is a biopharmaceutical company focused on serving patients with severe and rare disorders through the innovation, development and commercialization of life-transforming therapeutic products. Alexion is the global leader in complement inhibition and has developed and markets Soliris® (eculizumab) as a treatment for patients with PNH and aHUS, two debilitating, ultra-rare and life-threatening disorders caused by chronic uncontrolled complement activation. Soliris is currently approved in nearly 50 countries for the treatment of PNH and in nearly 40 countries for the treatment of aHUS. Alexion is evaluating other potential indications for Soliris in additional severe and ultra-rare disorders beyond PNH and aHUS, and is developing other highly innovative biotechnology product candidates, including asfotase alfa, across multiple therapeutic areas. This press release and further information about Alexion can be found at: www.alexionpharma.com.
[ALXN-G]
Safe Harbor Statement
This news release contains forward-looking statements, including statements related to potential medical benefits of Soliris® (eculizumab) for the prevention of delayed graft function (DGF) after kidney transplantation. 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 prevention of DGF after kidney transplantation, delays in arranging satisfactory manufacturing capabilities, the possibility that results of clinical trials are not predictive of safety and efficacy results of Soliris for prevention of DGF in broader or different patient populations, decisions of regulatory authorities to require additional testing, the risk that estimates regarding the number of patients at risk of DGF and observations regarding the natural history of patients with DGF are inaccurate, and a variety of other risks set forth from time to time in Alexion's filings with the
References
1 Irish WD, Ilsley JN, Schnitzler MA, Feng S, Brennan DC. A risk prediction model for delayed graft function in the current era of deceased donor renal transplantation. Am J Transplant. 2010;10(10):2279-86.
2 Yarlagadda SG, Coca SG, Garg AX, et al. Marked variation in the definition and diagnosis of delayed graft function: a systematic review. Nephrol Dial Transplant. 2008;23:2995-3003.
3 Jayaram D, Kommareddi M, Sung RS, Luan FL. Delayed graft function requiring more than one-time dialysis treatment is associated with inferior clinical outcomes. Clin Transplant. 2012;26(5):E536-43.
4 Siedlecki A, Irish W, Brennan DC. Delayed graft function in the kidney transplant. Am J Transplant. 2011;11:2279-96.
5 Perico N, Cattaneo D, Sayegh MH, Remuzzi G. Delayed graft function in kidney transplantation. Lancet. 2004;364:1814-27.
6 Cavaille-Coll M, Bala S, Velidedeoglu E, Hernandez A, Archdeacon P, Gonzalez G, et al. Summary of
7 Mosby's Dictionary of Complementary and Alternative Medicine.
8 Bonventre JV. Pathophysiology of acute kidney injury: roles of potential inhibitors of inflammation. Contrib Nephrol. 2007;156:39-46.
9 Damman J, Hoeger S, Boneschansker L, Theruvath A, Waldherr R, Leuvenink HG, et al. Targeting complement activation in brain-dead donors improves renal function after transplantation. Transpl Immunol. 2011;24(4):233-7.
10 Zhou W, Medof ME, Heeger PS, Sacks S. Graft-derived complement as a mediator of transplant injury. Curr Opin Immunol. 2007;19(5):569-76.
11 Thurman JM, Lenderink AM, Royer PA, Coleman KE, Zhou J, Lambris JD, et al. C3a is required for the production of CXC chemokines by tubular epithelial cells after renalishemia/reperfusion. J Immunol. 2007;178(3):1819-28.
12 Yarlagadda SG, Klein CL,
13 Butala NM, Reese PP, Doshi MD, Parikh CR. Is delayed graft function causally associated with long-term outcomes after kidney transplantation? Instrumental variable analysis. Transplantation. 2013;95:1008-14.
14 Yarlagadda SG, Coca SG, Formica RN Jr, Poggio ED, Parikh CR. Association between delayed graft function and allograft and patient survival: a systematic review and meta-analysis.
15 US Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipients. OPTN/SRTR Annual Report, 2009. Chapter II: Organ donation and utilization in
16 Eurotransplant.
Alexion:
Media:
Executive Director, Corporate Communications
or
Senior Director, Corporate Communications
or
Investors:
Executive Director, Investor Relations
Source:
News Provided by Acquire Media