Ravulizumab in paroxysmal nocturnal hemoglobinuria: a profile of its use

Ravulizumab (Ultomiris™) is a humanized monoclonal antibody that inhibits terminal complement C5, thereby reducing hemolysis, inflammation, and thrombosis in patients with paroxysmal nocturnal hemoglobinuria (PNH). Ravulizumab was developed by re-engineering eculizumab to create a longer-acting antibody, which allows an 8-weekly administration schedule instead of the 2-weekly schedule required with eculizumab. A single intravenous infusion of ravulizumab provides immediate and complete inhibition of serum free C5. With continued ravulizumab treatment, breakthrough hemolysis rates decrease as a result of eliminating free C5-associated breakthrough hemolysis. The efficacy of ravulizumab is noninferior to that of eculizumab, as determined in complement-inhibitor naive patients and those previously treated with eculizumab. Ravulizumab was generally well tolerated, with a generally comparable tolerability profile to that of eculizumab.