Eculizumab (Soliris)

Background

Eculizumab (Soliris) is FDA-approved for the treatment of atypical hemolytic uremic syndrome (aHUS) in adult and pediatric patients to inhibit complement-mediated thrombotic microangiopathy (TMA) and also for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis. Eculizumab is not indicated for the treatment of patients with Shiga toxin E coli—related hemolytic uremic syndrome (STEC-HUS).^1,2

Pharmacology/Pharmacokinetics

Eculizumab is a monoclonal antibody that binds with high affinity to complement protein C5 and prevents the generation of the terminal complement complex C5b-9. In patients with PNH, eculizumab inhibits terminal complement—mediated intravascular hemolysis and in patients with aHUS, eculizumab inhibits complement-mediated TMA.^1,2 Minimal eculizumab is excreted in urine with small quantities of immunoglobulin found in bile. The elimination half-life for PNH patients is 8 to 15 days and for aHUS patients, the elimination half-life is approximately 12 days.^1,2

Dosing and Administration

Eculizumab dosing for adults with PNH is 600 mg IV every 7 days for the first 4 weeks, then 900 mg IV for the fifth dose 7 days later, then 900 mg every 14 days thereafter. Eculizumab dosing for adults with aHUS is 900 mg IV every 7 days for the first 4 weeks, then 1200 mg IV for the fifth dose 7 days later, then 1200 mg IV every 14 days thereafter. Pediatric dosing is based on body weight, with doses ranging from 300 mg to 900 mg.^1,2 Eculizumab should be administered by IV infusion over 35 minutes via an infusion pump; it should not be administered as an IV push or bolus injection. Eculizumab should be diluted to a final concentration of 5 mg/mL by adding appropriate amounts of 0.9% sodium chloride (NaCl), 0.45% NaCl, 5% dextrose in water (D5W), or Ringer’s injection. The final infusion volume is 60 mL for 300-mg doses, 120 mL for 600-mg doses, 180 mL for 900-mg doses, and 240 mL for 1200-mg doses.^1,2

Clinical Efficacy

In clinical trials of eculizumab in PNH patients, significant reductions in lactate dehydrogenase (LDH) levels were achieved within the first week of treatment, with near-normal levels achieved at week 2 and maintained up to 36 months in certain patients. Eculizumab achieved rapid and sustained efficacy, regardless of baseline LDH levels or platelet counts.¹ In adults with PNH, eculizumab treatment for 26 weeks achieved stabilization of hemoglobin levels in significantly more patients than placebo treatment, and reduced the need for packed red cell transfusions to a significantly greater extent than placebo. Eculizumab was also associated with significant improvements in fatigue and health-related quality-of-life scores in several trials.³

There are limited published studies available on eculizumab in aHUS patients; however, reduction in terminal complement activity has been observed in patients receiving eculizumab. Additionally, eculizumab reduced signs of complement-mediated TMA activity, as shown by an increase in mean platelet counts from baseline to 26 weeks.^1,2

Medication Safety

Eculizumab therapy increases the risk of serious meningococcal infections, which can be fatal if not treated early. Patients must have received a meningococcal vaccine at least 2 weeks before the first dose of eculizumab unless already immunized; however, a booster dose may be required. Common adverse effects occurring in ≥30% of adult patients include hypertension, upper respiratory tract infection, headache, and diarrhea.^1,2

Product Availability and Cost Considerations

Eculizumab is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) and is supplied as 300-mg single-use vials containing 30 mL of 10 mg/ mL sterile, preservative-free solution per vial. Vials must be stored in the original carton until time of use under refrigerated conditions at 2° to 8° C (36o to 46° F) and protected from light. The vials should not be frozen, shaken or used beyond the expiration date stamped on the carton. The acquisition cost of Soliris is $6830 per 300-mg vial; the cost per dose would range between $6830 and $27,320, depending on dose and indication. Complete prescribing information is available at www.soliris.com.^1,2

Ashley N. Lewis, PharmD, BCPS, is a drug information specialist at University of North Carolina Hospitals (UNCH). She is currently the pharmacy and therapeutics secretary at UNCH and manages the day-to-day operations of the Drug Information Center and serves as a clinical assistant professor at the UNC Eshelman School of Pharmacy.

References

• Soliris [package insert]. Cheshire, CT: Alexion Pharmaceuticals, Inc; December 2012.
• Eculizumab. In: DRUGDEX System [Internet database]. Greenwood Village, CO: Thomson Reuters (Healthcare) Inc. Updated periodically.
• McKeage K. Eculizumab: a review of its use in paroxysmal nocturnal haemoglobinuria. Drugs. 2011;71(17):2327-2345.