ParagonRx® | Minimize Risk and Optimize Use

The U.S. Food and Drug Administration (FDA) granted accelerated approval for eculizumab (Soliris, Alexion Inc.) for the treatment of pediatric and adult patients with atypical hemolytic uremic syndrome (aHUS).

Eculizumab is a monoclonal antibody that inhibits the production of the terminal complement components C5a and the membrane attack complex C5b-9 by binding to complement protein C5. Prevention of C5a formation and the terminal complement complex inhibits complement-mediated thrombotic microangiopathy in patients with aHUS.

Administered as an intravenous infusion, the recommended dosing for adult patients with aHUS is 900 mg weekly for the first 4 weeks, followed by 1200 mg weekly one week later, and 1,200 mg every 2 weeks thereafter. The dosage regimen for pediatric patients is based upon body weight.

Two prospective single arm trials enrolling 37 adult and adolescent patients with aHUS and one retrospective trial of 19 pediatric patients and 11 adult patients with aHUS were reviewed. In a prospective trial of adult and adolescent patients with aHUS that was resistant to plasma therapy, eculizumab resulted in elimination of the requirement for dialysis, sustained improvement in the estimated glomerular filtration rate (eGFR), and sustained improvement in hematologic parameters that correlate with aHUS disease activity. Four of the five patients who required dialysis at entry were able to discontinue dialysis for the duration of eculizumab treatment. A median improvement in eGFR of at least 15 ml/min/1.73 m2 was observed in 53% of patients enrolled for a median duration of 251 days.

Hematologic normalization (achievement or maintenance of normal platelet counts and LDH levels for at least four weeks) was achieved in 76% of patients for a median duration of 37 weeks. These findings were supported by elimination of the requirement for plasma therapy in the majority of patients and improvement in other laboratory markers of hemolysis and evidence for suppression of terminal complement activity.

In the second prospective trial of adult and adolescent patients who required chronic plasma therapy, eculizumab treatment allowed cessation of plasma therapy and maintained renal function, as indicated by stable dialysis requirements and eGFR parameters. A total of 90% of patients maintained hematologic normalization after discontinuing chronic plasma therapy. The median duration of hematologic normalization was 38 weeks.

The outcomes of 19 pediatric patients in a retrospective trial were consistent with the outcomes observed in the prospective studies. Four of eight (50%) pediatric patients who previously required dialysis were able to discontinue dialysis after eculizumab therapy. Additionally, 37% of pediatric patients exhibited an improvement in eGFR of at least 15 mg/min/1.73 m2, and 42% of pediatric patients achieved or maintained normal hematologic parameters for at least four weeks. These findings are supported by an elimination of the requirement for plasma therapy in the majority of patients.

Eculizumab previously received approval for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) in March 2007.