Patients with paroxysmal nocturnal hemoglobinuria (PNH) treated with pegcetacoplan experienced a rapid stabilization of hemoglobin and lactate dehydrogenase (LDH) levels compared with best supportive care, according to the results of the phase 3 PRINCE study presented at Annual Meeting of the Society of Hematologic Oncology (SOHO).

“Pegcetacoplan represents a new effective therapeutic option with a favorable safety profile for patients with PNH,” the authors wrote.

In the primary results of the PRINCE trial, pegcetacoplan, a C3 inhibitor, effectively stabilized hemoglobin and LDH at week 26 compared with baseline. The aim of this post hoc analysis was to evaluate the effect of pegcetacoplan on hemoglobin and LDH levels over time in the PRINCE cohort.

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The open-label, phase 3 PRINCE trial randomly assigned 53 adult patients with PNH who were anemic and complement-naïve 2:1 to receive pegcetacoplan or best supportive care for 26 weeks. An additional 11 patients were treated with pegcetacoplan after escape from control on best supportive care. None of the patients had received prior eculizumab or ravulizumab.

Patients had a hemoglobin level that was below the lower limits and LDH at 1.5x or higher the upper limit of normal (ULN). The mean age of the cohort was 47 and the mean years since diagnosis of PNH was 4.

Stabilization of hemoglobin levels was rapid after administration of pegcetacoplan, with levels reaching 12 g/dL at day 6. Patients who received best supportive care only demonstrated hemoglobin levels that remained at a mean of approximately 7 to 10 g/dL through week 26.

Pegcetacoplan also resulted in rapid stabilization of LDH levels to between approximately 100 and 200 U/L, occurring by day 2. Patients in the best supportive care arm demonstrated mean LDH levels of approximately 1500 to 2000 U/L through week 26.

The improvement in hemoglobin and LDH levels among patients treated with pegcetacoplan corresponded with improvement in fatigue, as measured by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score. Fatigue rebounded to normal levels by day 4 in the pegcetacoplan arm, whereas fatigue scores remained below normal in the best supportive care arm.

The rates of serious adverse events (AEs) was higher in the supportive care group at 16.7% compared with 8.7% in the pegcetacoplan arm; however, none of the serious AEs were considered related to pegcetacoplan and there were no discontinuations due to AEs.

The most common treatment-emergent AEs were injection site reaction, hypokalemia, dizziness, and fever in the pegcetacoplan arm. Infections occurred more frequently in the supportive care arm, whereas hypersensitivity reactions were more common in the pegcetacoplan arm.

The authors concluded that “pegcetacoplan treatment rapidly stabilized hemoglobin in complement inhibitor-naïve patients experience a substantial hemoglobin decrease.” They added that “LDH levels decreased to within normal range, suggesting control of intravascular hemolysis and prevention of extravascular hemolysis.”


Yeh M, Wong R, Al-Adhami M, et al. Pegcetacoplan rapidly stabilizes complement inhibitor naïve patients with paroxysmal nocturnal hemoglobinuria experiencing hemolysis with acute hemoglobin decreases: PRINCE trial post hoc analysis. Presented at: Annual Meeting of the Society of Hematologic Oncology (SOHO); September 28-October 1, 2022. Abstract MDS-113.