HUS Foundation

Alexion To Begin Clinical Trials of Soliris® in aHUS Patients

New England Journal of Medicine Publishes Case Reports on the Investigational Use of Soliris (eculizumab) in Patients with Atypical Hemolytic Uremic Syndrome (aHUS)

Alexion To Begin Clinical Trials of Soliris® in aHUS Patients
CHESHIRE, Conn.--(BUSINESS WIRE)--Jan 29, 2009 - Two separate case reports published today in the New England Journal of Medicine (NEJM) examine the investigational use of Soliris ® (eculizumab), a terminal complement inhibitor developed by Alexion Pharmaceuticals, Inc. (Nasdaq: ALXN), in patients with a rare and severe inflammatory disease called atypical Hemolytic Uremic Syndrome (aHUS). In both cases, physicians observed a significant reduction in the destruction of red blood cells, reduced platelet consumption and improved kidney function following Soliris therapy.

Separately, Alexion announced today that it is currently initiating clinical trials of eculizumab in patients with aHUS. Soliris is approved in the United States, European Union, and Canada for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH).

Atypical Hemolytic Uremic Syndrome is characterized by hemolysis, thrombocytopenia and clotting of blood vessels (microangiopathy), particularly in the kidney and brain, often progressing to end-stage kidney disease. Like PNH, aHUS is caused by a deficiency in normally occurring complement inhibitors. Typically, patients with aHUS have genetic mutations in one of several complement inhibitor proteins that lead to uncontrolled complement activation. Excessive complement activation may contribute to severe inflammation of the blood vessels and blood clotting through the activation of white blood cells, platelets, and the endothelial cell lining of blood vessels. (1) The prognosis for patients with aHUS is poor. Approximately 70% of patients with the most common mutation experience chronic renal insufficiency, chronic dialysis, or death by one year after the first clinical episode. (2) Following kidney transplantation, recurrent aHUS causes kidney transplant failure in approximately 62 - 88% of patients. (3)

Case Reports
In a case report submitted to the NEJM by Ralph A. Gruppo, M.D., Director of the Comprehensive Hemophilia and Thrombosis Center at the Cincinnati Children's Hospital Medical Center, an 18-month-old infant was admitted to the hospital following a fourth clinically severe relapse of congenital aHUS. During this episode, the patient did not respond to daily plasmapheresis, a procedure whereby proteins are removed from the blood by circulating the patient's blood through a machine. When the patient's condition deteriorated further, the physician administered Soliris. Complete blockade of terminal complement was observed in this patient, and hematologic and renal improvement began within 48 hours after initiation of treatment. Plasmapheresis was discontinued within the first week of eculizumab treatment and clinical remission was sustained throughout the 60 day observation period. The report further notes that eculizumab therapy is ongoing for over four months, to date, with sustained disease remission and no further plasma therapy intervention.

“It is well known that aHUS is a devastating disease without effective treatment options,” explained Dr. Gruppo, lead author of the report. “Further, after clinical worsening, there may be virtually nothing a physician can do to prevent further kidney damage and eventual kidney failure. Based on this initial and very limited experience, further studies of terminal complement inhibition with eculizumab are warranted.” In a second case reported in the same issue of the NEJM by Dr. Jens Nuernberger of the Department of Nephrology at University Duisburg-Essen in Essen, Germany, a 37-year-old woman with a history of kidney failure due to aHUS and loss of her first kidney transplant due to recurrent aHUS, was admitted to the hospital with progressive and severe aHUS shortly after her second kidney transplant. The patient's aHUS condition continued to clinically worsen despite extensive plasma treatments, indicating a high probability that the second kidney transplant would fail. After the administration of eculizumab, hemolysis quickly resolved, platelet count rebounded and kidney transplant function recovered. The patient's renal graft function has remained stable. Eculizumab appeared to be well tolerated in these two patients, with safety observations that have been consistent with those reported from controlled trials with eculizumab in patients with PNH. "There is a profound need to improve the management of aHUS. We are encouraged by the initial clinical experience with eculizumab in a very limited number of aHUS patients, and we are undertaking prospective clinical trials to investigate the role of complement inhibition in this condition," said Leonard Bell, M.D., Chief Executive Officer of Alexion.

Upcoming Clinical Studies Alexion is currently initiating four prospective, open-label clinical studies of eculizumab as a treatment for patients with aHUS in North America and multiple European countries: two studies of patients who are plasma therapy sensitive (one in adults and one in adolescents) and two studies of patients who are plasma therapy resistant (one in adults and one in adolescents). Information on the trials can be requested by e-mail using the address clinicaltrials@alxn.com, or by visiting the Alexion website at www.alexionpharma.com and clicking on the clinical trials link. The trials also will be posted to the www.clinicaltrials.gov website maintained by the U.S. National Institutes of Health.