Bone Marrow Failure Disorders

At the 63rd Annual Meeting of the American Society of Hematology (ASH), an international team of investigators reported findings of the phase 3 Prince trial of the C3-inhibitor pegcetacoplan vs standard-of-care therapy (excluding complement inhibitors) in adults with paryoxysmal nocturnal hemoglobinuria (PNH). While C5 inhibitors (eculizumab/ravulizumab) are often used to prevent intravascular hemolysis in PNH, these agents cannot prevent extravascular hemolysis (EVH); in contrast, pegcetacoplan, recently approved by the US Food and Drug administration for treatment of PNH, both controls IVH and prevents EVH. The Prince study enrolled 53 complement inhibitor–naive adults with PNH whose hemoglobin (Hb) levels were below the lower limit of normal and lactate dehydrogenase levels at least 1.5 times the upper limit of normal (ULN). Patients were randomized 2:1 to receive pegcetacoplan or standard-of-care (SoC) treatment that excluded complement inhibitors, for a period of 26 weeks. Through week 26, Hb stabilization was achieved by 85.7% of PEG-treated patients and 0 patients in the SoC group (P <.0001). Patients treated with PEG also demonstrated greater reductions in mean LDH levels from baseline to Week 26 (P <.0001) and at week 26 their mean LDH level (204.6 U/L) was below the ULN for LDH (226.0 U/L). The risk-benefit profile of pegcetacoplan was favorable and its safety profile was similar to that observed in previous studies, reported the investigators, who concluded that their results "provide evidence for the safety and efficacy of PEG treatment in complement-inhibitor naive patients with PNH."