Iptacopan monotherapy resulted in increased hemoglobin level in patients with PNH and hemoglobin ≥10 g/dL after anti-C5 therapy

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) on anti-C5 often experience extravascular hemolysis hemolysis: (hi-MOL-uh-suss) The destruction of red blood cells. with 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. . Iptacopan Iptacopan: FABHALTA, a complement factor B inhibitor, is the first oral medication approved to treat adults with paroxysmal nocturnal hemoglobinuria (PNH). It was approved by the U.S. Food and Drug Administration in December 2023. Fabhalta is taken twice a day in a capsule form. What is FABHALTA? … , the first oral proximal complement inhibitor targeting factor B, has shown efficacy and safety in PNH patients. APPULSE-PNH (NCT05630001), a phase 3b, single‑arm, open-label trial, enrolled adult patients with PNH and 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. ≥10 g/dL on stable anti-C5 for ≥6 months. Patients switched to iptacopan monotherapy (200 mg twice daily; 24 weeks). Primary endpoint: mean hemoglobin change from baseline across four visits (Days 126-168). At baseline, 57.7% of patients had elevated absolute reticulocyte reticulocyte: An immature red blood cell. Reticulocytes are normally found in the bone marrow. They are present in the bloodstream only in very low numbers. counts (ARCs; above ULN = 123 × 109/L) and 50% had C3 deposition on red blood cells (RBCs) >10%, indicative of extravascular hemolysis. There was a statistically significant increase in hemoglobin during the trial; adjusted mean change from baseline (95% CI) was +2.0 g/dL (1.7-2.3) overall, and in patients with baseline hemoglobin <12 g/dL and ≥12 g/dL, +2.4 (2.0-2.7) and +1.4 (1.0-1.8), respectively. Patients maintained transfusion independence transfusion independence: No longer needing any type of blood transfusion. , 92.7% with hemoglobin ≥12 g/dL. Adjusted mean change from baseline (95% CI) in 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… and ARC were -1.3% (-6.6 to 4.3) and -89.2 × 109/L (-95.5 to -82.9), respectively. Mean (SD) proportion of C3d+ PNH RBCs, assessed by flow cytometry flow cytometry: (sy-TOM-uh-tree) A laboratory test that gives information about cells, such as size, shape, and percentage of live cells. Flow cytometry is the test doctors use to see if there are any proteins missing from the surface of blood cells. It is the standard test for confirming a diagnosis of paroxysmal… , decreased from 11.0% (8.6) to 0.2% (0.7) at Day 168. No patients had breakthrough hemolysis or major adverse vascular events. FACIT-Fatigue and treatment satisfaction scores improved by Days 84 and 168. Safety showed consistency with previous iptacopan PNH trials. Iptacopan improved hematologic outcomes in PNH patients with hemoglobin ≥10 g/dL on anti-C5, maintaining control of intravascular hemolysis and resolving extravascular hemolysis.