Plain language summary of PEGASUS, a study comparing pegcetacoplan with eculizumab for 16 weeks in people with paroxysmal nocturnal hemoglobinuria

Abstract

This plain language summary is about a phase 3 clinical trial called PEGASUS. The PEGASUS trial studied adults with paroxysmal nocturnal hemoglobinuria (PNH), a rare blood disorder usually acquired in adulthood without a known cause. Patients with PNH have defects in the complement system, which is part of the immune defense system. This complement defect results in the destruction of red blood cells; this is called hemolysis. Hemolysis then causes anemia. People with anemia do not have enough red blood cells to carry oxygen around the body, which can cause fatigue (extreme tiredness), shortness of breath, or headache. Anemia can be measured by the level or amount of hemoglobin in the blood. Hemolysis can be measured by the amount of hemoglobin, lactate dehydrogenase (LDH), and reticulocytes in the blood. Hemoglobin and LDH are proteins inside red blood cells. In patients with PNH, hemolysis causes hemoglobin levels to go down and LDH levels go up. Reticulocytes are immature red blood cells; their level goes up during hemolysis to replace destroyed red blood cells. Eculizumab is the current standard of care for patients with PNH. Eculizumab is a medicine that blocks or inhibits the complement component 5 (C5). Pegcetacoplan is a new medicine, the first that inhibits the complement component C3. The PEGASUS study compared the new medicine pegcetacoplan with eculizumab in adults with PNH who remained anemic even after being treated with eculizumab for at least 3 months. In PEGASUS, 41 participants received pegcetacoplan and 39 people received eculizumab for 16 weeks. The trial results showed that pegcetacoplan decreased signs of hemolysis compared to eculizumab. Participants treated with pegcetacoplan for 16 weeks had increased blood levels of hemoglobin, and decreased levels of LDH and reticulocytes; also, 85% of them no longer needed a blood transfusion compared with 15% of those treated with eculizumab. A patient survey showed that 73% of patients who received pegcetacoplan had decreased fatigue. None of the participants treated with eculizumab had decreased fatigue. Most participants in both treatment groups had side effects. However, no serious infections or thrombosis (blood clots) occurred with either treatment group. Episodes of hemolysis during treatment, called breakthrough hemolysis, happened in 10% of pegcetacoplan- and 23% of eculizumab-treated participants. Pegcetacoplan reduced the level of hemolysis in adults with PNH better than eculizumab did. Pegcetacoplan was well tolerated by most patients in this study. Clinical Trial Registration: NCT03500549 (PEGASUS) ( ClinicalTrials.gov )