Pegcetacoplan rapidly boosts hemoglobin and cuts transfusions in PNH patients refractory to prior therapies.

Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare, life-threatening blood disorder characterized by chronic intravascular hemolysis due to uncontrolled complement activation. While terminal complement inhibitors (e.g., C5 inhibitors like eculizumab or ravulizumab) effectively manage many PNH patients, a significant subset experiences an unsatisfactory hematological response, often due to persistent extravascular hemolysis or breakthrough hemolysis. This leaves a critical gap for patients who do not achieve adequate hemoglobin levels or remain transfusion-dependent. Targeting the proximal complement protein C3 with inhibitors like Pegcetacoplan offers a promising strategy to address this by blocking the complement cascade earlier.

This non-interventional, retrospective, multicenter study analyzed real-world clinical and hematological data from the first 32 PNH patients in Spain treated with Pegcetacoplan. All patients had previously shown an unsatisfactory response to terminal complement inhibitors. Data was collected over a median treatment duration of 13 months (range 4-61 months). Key endpoints included changes in hemoglobin levels, packed red blood cell (PRBC) transfusion requirements, incidence of breakthrough hemolysis, safety profile, and physician-perceived health-related quality of life.

Treatment with Pegcetacoplan led to rapid and significant improvements in hematological parameters. Patients experienced a median increase in hemoglobin of 2.65 g/dL within just 4 weeks. Notably, 56.3% of patients achieved a >2 g/dL increase in hemoglobin. Hemoglobin levels reached >8 g/dL in 93.7% of patients, >10 g/dL in 87.5%, and >12 g/dL in 46.9%. Transfusion requirements dramatically decreased: the proportion of patients requiring PRBC transfusions fell from 62.5% at baseline to 15.6% after Pegcetacoplan initiation.

Breakthrough hemolysis incidence also significantly dropped from 34.4% to 9.4% after 6 months of treatment. The safety profile was favorable, with no reported thrombosis and only mild adverse events described in 11 patients. Physicians also observed important enhancements in patients' health-related quality of life.