Purpose: The pharmacology, pharmacokinetics, indications, clinical efficacy, adverse effects, drug interactions, and dosage and administration of eculizumab are reviewed.
Summary: Eculizumab, a recombinant, humanized, monoclonal, immunoglobulin G antibody produced from murine myeloma cells, is the first agent to be approved for labeling by the Food and Drug Administration for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). Eculizumab works by inhibiting the complement cascade. It binds specifically to complement protein C5 and inhibits cleavage to C5a and C5b, resulting in the prevention of terminal complex formation and therefore cell lysis. In clinical studies, the effect of eculizumab on hemolysis was measured by a reduction in serum lactase dehydrogenase levels. The effect on hemolysis was evident after one week of treatment. The safety and efficacy of eculizumab were evaluated in a series of three trials. Results from the trials indicated that eculizumab reduces hemolysis and improves symptoms such as the number of paroxysms, dysphagia, and abdominal pain. The most frequent adverse reactions reported in the clinical trials included headache, nasopharyngitis, back pain, and nausea. The recommended i.v. dosing regimen is 600 mg weekly for four weeks, followed by a 900-mg dose at week 5, and 900 mg every 14 days as a maintenance dose. The manufacturer recommends that patients who have not received meningococcal vaccine be vaccinated at least two weeks before starting therapy because eculizumab is associated with a high risk of meningococcal infection.
Conclusion: Eculizumab represents a major advancement in the treatment of PNH. While clinical experience is limited, long-term studies in patients with PNH have supported the safe and effective use of eculizumab with few serious adverse effects.