Plain language summary: treatment of paroxysmal nocturnal hemoglobinuria with pegcetacoplan for 48 weeks (PEGASUS study)

What is this summary about? Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, serious blood disease, characterized by uncontrolled activation of the complement system that causes hemolysis (destruction of red blood cells). The complement component 5 (C5) inhibitor eculizumab was the first approved treatment for PNH. The PEGASUS trial compared eculizumab with pegcetacoplan, a new complement component 3 (C3) inhibitor. Because C3 is activated before C5, blocking C3 would also block C5; thus, a C3 inhibitor might prevent hemolysis more completely than a C5 inhibitor in patients with PNH. During the first 16 weeks of PEGASUS, patients received either pegcetacoplan or eculizumab; results were published separately. This summary describes results of the following 32 weeks of PEGASUS, during which all patients received pegcetacoplan to evaluate if pegcetacoplan continued to be effective and safe for up to 48 weeks. What were the results? Pegcetacoplan continued to be effective in participants who received it throughout the study and improved symptoms in participants who switched from eculizumab. The most common adverse events (side effects) were skin irritation at the injection site, hemolysis, nasopharyngitis (runny nose and sore throat), and diarrhea. Adverse events were serious and related to pegcetacoplan in 4 of 77 (5%) patients; all patients recovered from these events. What do the results mean? Pegcetacoplan improved symptoms and was well tolerated for up to 48 weeks by most patients in PEGASUS, suggesting that adult patients with PNH may benefit from long-term pegcetacoplan treatment.