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Medical Areas: Hematology | Nephrology | Family Medicine
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The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Approval Status: Approved September 2011
Treatment Area: atypical hemolytic uremic syndrome
Soliris (eculizumab) is a recombinant humanized monoclonal IgG2/4delta antibody. It specifically binds to the complement protein C5 with high affinity.
Soliris is specifically indicated for atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy.
Soliris is supplied as a solution for intravenous administration. The recommended dose of Soliris for adults 18 years of age and older is 900 mg weekly for the first four weeks, followed by 1200 mg for the fifth dose one week later, then 1200 mg every two weeks thereafter. The recommended dose of Soliris for pediatrics under the age of 18 years is based on body weight.
The FDA approval of Soliris for atypical hemolytic uremic syndrome was based on three single-arm studies: two prospective (aHUS Studies 1 and 2) and one retrospective study (aHUS Study 3). In all studies, the dose of Soliris in adult and adolescent patients was 900 mg every 7 days for four weeks, followed by 1200 mg 7 days later, then 1200 mg every 14 days thereafter. The dosage regimen for pediatrics weighing less than 40 kg enrolled in aHUS Study 3 was based on body weight. Efficacy evaluations were based on thrombotic microangiopathy (TMA) endpoints. These endpoints included platelet count change from baseline, hematologic normalization, complete TMA response, TMA-event free status and daily TMA intervention rate.
aHUS Resistant to PE/PI (aHUS Study 1)
This trial enrolled 17 subjects who displayed signs of TMA despite receiving at least four PE/PI treatments the week prior to screening. The subjects received Soliris for a minimum of 26 weeks. Soliris reduced signs of complement-mediated
TMA activity, as shown by an increase in mean platelet counts from baseline to 26 weeks. The mean platelet count increased from 109 x10(9)/L at baseline to 169 x10(9)/L
by one week; this effect was maintained through 26 weeks (mean platelet count at week 26: 210 x10(9)/L). Renal function, as measured by median eGFR, was improved during Soliris therapy. Four of the five subjects who required dialysis at study entry were able to discontinue dialysis for the duration of Soliris treatment.
aHUS Sensitive to PE/PI (aHUS Study 2)
This trial enrolled 20 subjects undergoing chronic PE/PI who generally did not display hematologic signs of ongoing thrombotic microangiopathy. The subjects received Soliris for a minimum of 26 weeks. Soliris
reduced signs of complement-mediated TMA activity, as shown by an increase in mean
platelet counts from baseline to 26 weeks. Platelet counts were maintained at normal levels despite the elimination of PE/PI. The mean platelet count was 229 x 10(9)/L at baseline, and 233 x10(9)/L at week 26. Renal function, as measured by median eGFR, was maintained during Soliris therapy.
Retrospective Study in Patients with aHUS (aHUS Study 3)
This trial enrolled 19 pediatrics (ages 2 months to 17 years) who received Soliris for a median duration of 16 weeks. Soliris reduced signs of complement-mediated TMA activity, as shown by an increase in mean platelet counts from baseline. Mean platelet count increased from 171 x10(9)/L at baseline to 233 x10(9)/L after one week of therapy; this effect was maintained through 26 weeks (mean platelet count at week 26: 254 x10(9)/L). Nine subjects experienced an eGFR improvement of at least 15 mL/min/1.73 m2.
Adverse events associated with the use of Soliris for atypical hemolytic uremic syndrome may include, but are not limited to, the following:
- upper respiratory tract infection
- urinary tract infection
Mechanism of Action
Soliris is a monoclonal antibody that specifically binds to the complement protein C5 with high affinity, thereby inhibiting its cleavage to C5a and C5b and preventing the generation of the terminal complement complex C5b-9. Soliris inhibits complement mediated thrombotic microangiopathy (TMA) in patients with aHUS.
Tschumi S, Gugger M, Bucher BS, Riedl M, Simonetti GD Eculizumab in atypical hemolytic uremic syndrome: long-term clinical course and histological findings. Pediatric Nephrology 2011 Nov;26(11):2085-8. Epub 2011 Aug 30
Köse O, Zimmerhackl LB, Jungraithmayr T, Mache C, Nürnberger J New treatment options for atypical hemolytic uremic syndrome with the complement inhibitor eculizumab. Seminars in thrombosis and hemostasis 2010 Sep;36(6):669-72
Mache CJ, Acham-Roschitz B, Frémeaux-Bacchi V, Kirschfink M, Zipfel PF, Roedl S, Vester U, Ring E Complement inhibitor eculizumab in atypical hemolytic uremic syndrome. Clinical Journal of the American Society of Nephrology 2009 Aug;4(8):1312-6
For additional information regarding Soliris or atypical hemolytic uremic syndrome, please visit the Soliris web page.