Kidney Disorders
Alexion is initiating clinical trials to evaluate Soliris for the treatment for
patients with atypical Hemolytic Uremic Syndrome (aHUS). Independent investigators
have started a study to evaluate Soliris in patients at high risk for transplant rejection and in patients with Dense Deposit Disease (DDD).
Atypical Hemolytic Uremic Syndrome (aHUS)
aHUS is a rare and severe inflammatory disease characterized by the hemolytic destruction
of red blood cells, decreased platelets and clotting in blood vessels, particularly
in the kidney and brain, often progressing to kidney failure.
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, leading to uncontrolled complement activation. This excessive
complement activation may in turn contribute to severe inflammation of blood vessels
and blood clotting through the activation of white blood cells, platelets, and the
cell lining of blood vessels.34 The prognosis for patients with aHUS
is poor. Approximately 70% of patients with the most common mutation experience
poor kidney function, kidney dialysis, or death within a year of the first clinical
episode.35 Following kidney transplantation, recurrent aHUS causes kidney
transplant failure in approximately 62% - 88% of patients.36
In January 2009, the New England Journal of Medicine published two separate
case reports examining the investigational use of Soliris in patients with aHUS.37,38
In both cases, physicians observed a significant reduction in the destruction of
red blood cells, reduced platelet destruction and improved kidney function following
Soliris therapy.
Alexion is initiating four prospective, open-label clinical studies of eculizumab as a treatment for
patients with aHUS in North America and multiple European countries. These comprise
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).
High Risk Kidney Transplantation
Patients undergoing kidney transplantation may experience severe antibody-mediated
rejection (AMR) in the early post-transplant period, characterized by the acute
onset of kidney failure and rapid progression to destruction of the transplanted
kidney.
AMR results when antibodies in the transplant recipient vigorously attack the blood
vessels of the donated kidney. During severe AMR, these donor specific antibodies
(DSA) bind to the blood vessel lining of the donor organ and initiate activation
of the complement cascade, resulting in severe blood vessel inflammation and clotting.
Administration of a C5 Inhibitor in animal models of AMR inhibits complement activation,
tissue damage and transplant rejection.9
In May of 2008, an investigator-initiated clinical trial commenced to evaluate Soliris in presensitized
renal transplant patients. This trial is currently enrolling patients.
Interim results of this trial were presented at the American Transplant Congress
in June 2009.
Dense Deposit Disease (DDD)
DDD, also called Type II membrano-proliferative glomerulonephritis, is a rare and
severe kidney disease characterized by genetic mutations in complement inhibitor
genes that can lead to sustained complement activation and inflammation. In most
cases, the disease evolves into chronic renal failure, requiring dialysis and renal
transplantation. Independent physicians are evaluating the use of Soliris in patients
with DDD.