Atypical Hemolytic Uremic Syndrome (aHUS) is a rare, lifethreatening, chronic disease of
complement-mediated thrombotic microangiopathy (TMA) characterized by acute onset of renal
impairment, thrombocytopenia, and microangiopathic hemolytic anemia. The estimated incidence
of aHUS is approximately 0.5 per million per year. aHUS affects both adults and children, but
is observed primarily in children and young adults.
Atypical HUS commonly develops due to dysregulation of the alternative complement pathway and
can be sporadic (80%) or familial(20%).
The clinical course of aHUS is often unpredictable and can be dependent upon the specific
genetic abnormality present within the complement system, if any, and/or triggering events
associated with complement activation or inflammation, including autoimmune disease,
transplant, pregnancy, infection, metabolic conditions, and drug use. In patients with
dysregulated complement activity, such as those with complement mutations commonly observed
in aHUS, the kidney vasculature is often the site of thrombosis stemming from endothelial
injury.
Cemdisiran has been designed to reduce the level of C5 mRNA in the liver, thereby reducing
levels of circulating C5 protein, inhibiting terminal complement pathway activity, and
preventing formation and deposition of the MAC (C5-b9) on endothelial cells in the kidney. As
a result, complement-mediated endothelial cell damage in patients with aHUS and subsequent
progression to End Stage Renal Disease (ESRD) may be reduced.
Phase:
Phase 2
Details
Lead Sponsor:
Mario Negri Institute for Pharmacological Research