Hemolysis events in the Phase 3 PEGASUS study of pegcetacoplan in patients with paroxysmal nocturnal hemoglobinuria

Patients with paroxysmal nocturnal hemoglobinuria paroxysmal nocturnal hemoglobinuria: (par-uk-SIZ-muhl nok-TURN-uhl hee-muh-gloe-buh-NYOOR-ee-uh) A rare and serious blood disease that causes red blood cells to break apart. Paroxysmal means sudden and irregular. Nocturnal means at night. Hemoglobinuria means hemoglobin in the urine. Hemoglobin is the red part of red blood cells. A… (PNH) experience complement-mediated intravascular hemolysis hemolysis: (hi-MOL-uh-suss) The destruction of red blood cells. leading to anemia anemia: (uh-NEE-mee-uh) A condition in which there is a shortage of red blood cells in the bloodstream. This causes a low red blood cell count. Symptoms of anemia are fatigue and tiredness. , fatigue, and potentially life-threatening thrombotic complications. Pegcetacoplan Pegcetacoplan: EMPAVELI® is the first PNH treatment that binds to complement protein C3. It was approved by the Food and Drug Administration in May 2021 for treating adult patients with paroxysmal nocturnal hemoglobinuria (PNH). EMPAVELI is given skin (subcutaneously) by using the Empaveli injector or with an… , a C3 inhibitor, demonstrated sustained improvements in hematological and clinical parameters in the Phase 3 PEGASUS trial in patients with PNH who remained anemic despite C5 inhibitor therapy. The current post-hoc analysis describes 26 hemolysis adverse events (AEs) experienced in 19 patients during pegcetacoplan therapy in PEGASUS and baseline patient characteristics potentially associated with increased hemolysis risk. Lactate dehydrogenase Lactate dehydrogenase: (LAK-tate dee-high-DROJ-uh-nase) An enzyme found in the blood and in many of the body's organs. High levels of LDH in the blood can mean that red blood cells are breaking apart (hemolysis) or that there is tissue damage in the body. It is important for patients with paroxysmal nocturnal… (LDH) ≥2× the upper limit of normal (ULN) was observed in 19 events, including 2 with LDH ≥10× ULN. All patients experienced decreased hemoglobin hemoglobin: A protein in the red blood cells. Hemoglobin picks up oxygen in the lungs and brings it to cells in all parts of the body. during hemolysis (mean decrease: 3.0 g/dL). In 16 events (62%) a potential complement-amplifying condition underlying the event could be identified. Hemolysis AEs led to study discontinuation in 5 patients. However, 17 of 26 (65%) hemolysis AEs were manageable without pegcetacoplan discontinuation. A greater proportion of patients with hemolysis AEs (n=19) had key characteristics of higher disease activity at baseline compared to patients without hemolysis AEs (n=61), namely higher-than-label eculizumab eculizumab: Eculizumab (Soliris ®) is given as an IV into a vein at the doctor’s office or at a special center. The procedure usually takes about 35 minutes. You will probably get an IV once a week for the first 4 weeks. Starting in the 5th week, you will get a slightly higher dose of Soliris every 2 weeks. … dose (53% vs 23%), detectable CH50 (74% vs 54%) and ≥4 transfusions in the previous 12 months (68% vs 51%). These characteristics may be useful predictors of potential future hemolysis events. ClinicalTrials.gov identifier: NCT03500549.