Pegcetacoplan Compared with Supportive Care for 26 Weeks for Participants with Paroxysmal Nocturnal Hemoglobinuria: a Plain Language Summary

What is this summary about? This plain language summary describes the phase 3 PRINCE study. The study looked at adults with paroxysmal nocturnal hemoglobinuria (PNH), a rare blood disorder that is acquired (not inherited), usually during adulthood. PNH causes hemolysis, which is the destruction of red blood cells. The PRINCE study compared a new medicine, pegcetacoplan, with the older treatment of supportive care (includes red blood cell blood transfusions; blood thinners; steroid medicines; and supplements, like iron, folate or vitamin B12). Supportive care was the standard treatment worldwide until eculizumab, the first C5 complement inhibitor medicine, was approved by the United States Food and Drug Administration and the European Medicines Agency in 2007 for the treatment of PNH. Supportive care is still the standard treatment for PNH in countries where C5 complement inhibitor medicines are not available. The PRINCE trial aimed to show if pegcetacoplan reduced hemolysis and if side effects occurred with pegcetacoplan in patients who had not received C5 complement inhibitor medicines recently. How was the study carried out? Participants were adults with PNH and anemia. Anemia was defined as a hemoglobin level of less than 13.6 grams per deciliter of blood for men and less than 12.0 grams per deciliter of blood for women. Hemoglobin is a protein inside red blood cells. Participants in the trial had not recently been treated with a C5 complement inhibitor medicine (eculizumab or ravulizumab). The participants were split into 2 groups: a pegcetacoplan group and a supportive care group. 35 participants received pegcetacoplan for 26 weeks, and 18 participants received supportive care. Those who received supportive care could switch to pegcetacoplan if their anemia got worse. Researchers monitored the participants' blood markers for hemolysis, how participants felt during the trial and the participants' side effects. The study started in 2019 and ended in 2021. What were the results? Participants who received pegcetacoplan had fewer signs of hemolysis after 26 weeks of treatment with pegcetacoplan compared with participants who received supportive care. Although participants in both groups had side effects, most were not serious. No serious side effects were related to pegcetacoplan. What do the results show? These results show that pegcetacoplan reduced hemolysis in adults with PNH better than supportive care. None of the side effects related to pegcetacoplan were serious. Results from the PRINCE study were published in Blood Advances in 2023.