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FDA Report: Eculizumab (Soliris®) for the Treatment of Patients with Paroxysmal Nocturnal Hemoglobinuria

Office of Oncology Drug Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA

Key Words. Eculizumab • Paroxysmal nocturnal hemoglobinuria • PNH • Drug approval

Correspondence: Andrew Dmytrijuk, M.D., Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland 20993, USA. Telephone: 301-796-2050; Fax: 301-796-9848; e-mail: andrew.dmytrijuk{at}fda.hhs.gov

Received April 8, 2008; accepted for publication July 21, 2008.

ABSTRACT

On March 16, 2007, eculizumab (Soliris®; Alexion Pharmaceuticals, Inc. Cheshire, CT), a humanized monoclonal antibody that binds to the human C5 complement protein, received accelerated approval by the U.S. Food and Drug Administration for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis. Eculizumab was studied in a randomized, double-blind, placebo-controlled clinical trial in 87 RBC transfusion–dependent adult PNH patients and in a supportive single-arm study in 96 patients. The eculizumab dose was 600 mg as a 35-minute i.v. infusion administered weekly for the first 4 weeks followed by 900 mg (week 5) then 900 mg every 14 days thereafter. Hemoglobin stabilized in 21 of 43 (48.8%) eculizumab-treated patients, compared with none of 44 placebo-treated patients. Eculizumab-treated patients required significantly fewer RBC transfusions than placebo-treated patients (median, 0 versus 10 units). There was also a significant reduction in the serum lactate dehydrogenase area under the curve with eculizumab compared with placebo treatment. Results of the phase II supportive study were similar to those of the phase III study. The safety database included 196 adult patients with PNH. Significant findings included the development of human anti-human antibody responses in three patients and serious meningococcal infections in three patients. Patients should undergo meningococcal vaccination at least 2 weeks prior to receiving the first eculizumab treatment and have revaccination according to current medical guidelines. Patients must be monitored and evaluated immediately for early signs of meningococcal infections and treated with antibiotics as indicated.

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