Pegcetacoplan Maintains Clinical Benefit in Paroxysmal Nocturnal Hemoglobinuria

An analysis of the PEGASUS and PRINCE clinical trials reported long-term efficacy of pegcetacoplan for patients with paroxysmal nocturnal hemoglobinuria (PNH) with or without prior treatment with a complement component 5 inhibitor (C5i). These findings were presented at the Society of Hematologic Oncology 2024 Annual Meeting in Houston, Texas.

The study included data from PEGASUS and PRINCE, which were both phase III clinical trials, along with a subsequent open-label extension. Patients received 1,080 mg of pegcetacoplan subcutaneously twice weekly, with possible dose escalations allowed. Efficacy was evaluated at 2.5 years (PRINCE) and three years (PEGASUS). Of the 133 patients originally enrolled in PEGASUS and PRINCE, 114 were enrolled in the extension.

Before initiation of pegcetacoplan, mean hemoglobin (Hb) levels were 8.95 g/dL in PEGASUS and 9.27 g/dL in PRINCE, and median baseline lactate dehydrogenase (LDH) levels were 217.0 U/L and 1,964 U/L, respectively. Treatment with pegcetacoplan led to significant improvements in Hb and LDH levels, which remained stable through 2.5 (PRINCE) and three years (PEGASUS). Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scores improved rapidly with treatment and were maintained in both trials, from 31.6 in PEGASUS and 36.6 in PRINCE at baseline to around the general population norm (43.6). Absolute reticulocyte count and indirect bilirubin values maintained improvement as well. Annual rates of transfusion avoidance ranged from 71% to 79% (PEGASUS) and 80% to 86% (PRINCE).

Adverse events (AEs) were common. Half of patients experienced a serious AE, and 4.5% of those were deemed treatment-related. Seventeen patients discontinued pegcetacoplan due to an AE; nine patients discontinued due to a hemolytic disorder, of which seven were in the first year of treatment. Four deaths (3.0%) occurred, although none were deemed pegcetacoplan-related. Three patients (2.3%) experienced a thrombotic event, and breakthrough hemolysis occurred in 28.8% of patients in PEGASUS and 30.8% in PRINCE. There were no cases of meningitis.

“This analysis shows sustained efficacy and continued safety of long-term pegcetacoplan for patients with PNH, regardless of prior C5i treatment,” the study investigators concluded.

Reference

de Castro C, Mulherin B, Patriquin CJ, et al. Efficacy and safety is maintained in adult patients with paroxysmal nocturnal hemoglobinuria receiving pegcetacoplan for up to three years. Abstract MDS-397. Presented at the Society of Hematologic Oncology 2024 Annual Meeting; September 4-7, 2024; Houston, Texas.