The recombinant humanised monoclonal IgG2/4k antibody is given in a dosing regimen that consists of a 4-week initial phase followed by a maintenance phase.
Rare genetic disease
aHUS is a rare chronic genetic disease defined by the presence of microangiopathic haemolytic anaemia, thrombocytopenia and acute renal failure. It is characterised by the formation of blood clots in small vessels throughout the body (thrombotic microangiopathy), which can cause life-threatening damage to the kidney, brain and other vital organs. Patients receiving eculizumab should be monitored for thrombotic microangiopathy by measurement of platelet counts, serum LDH and serum creatinine, and may require dose adjustment during the maintenance phase.
Eculizumab displayed efficacy in 3 trials: 2 prospective studies in a total of 37 patients (C08-002A/B and C08-003A/B) and 1 retrospective study in 30 patients (C09-001r). All participants received eculizumab.
The first prospective study included patients in the early stage of aHUS with evidence of clinical thrombotic microangiopathy (TMA) despite plasma exchange (PE) or plasma infusion (PI). Patients had a significant improvement in platelet count from baseline to week 26 (mean increase 73 x 109/L, p=0.0001) and 88% were TMA event-free (defined as having no decrease in platelet count, no PE or PI and no new dialysis). Renal function also improved and haematologic normalisation was achieved in 76% of patients.
The second prospective study included patients with long term aHUS, without evidence of TMA, and undergoing chronic PE or PI. Similar results were observed, with 80% of patients achieving TMA event-free status and 90% achieving haematologic normalisation.
The retrospective study enrolled 15 children aged 2 months to 12 years, who received eculizumab; efficacy results appeared consistent with those observed for patients enrolled in the pivotal adult studies.