Novartis announces results from Phase III APPOINT-PNH trial of iptacopan

Novartis announced detailed results from the Phase III APPOINT-PNH trial of investigational oral monotherapy iptacopan in complement-inhibitor-naive adults with paroxysmal nocturnal hemoglobinuria, PHN. The trial met its primary endpoint and demonstrated clinically meaningful benefits across secondary endpoints1. These data were presented at the 49th Annual Meeting of the European Society for Blood and Marrow Transplantation, EBMT. With iptacopan treatment, an estimated 92.2% of patients achieved a 2 g/dL or more hemoglobin-level increase from baseline without the need for red blood cell transfusions after the 24-week core treatment period. The APPOINT-PNH trial also showed clinically meaningful benefits for secondary endpoints. An estimated 62.8% of patients achieved hemoglobin levels of 12 g/dL or more without the need for red blood cell transfusions. Importantly, an estimated 97.6% of patients achieved red blood cell transfusion independence at 24 weeks. No clinical breakthrough hemolysis events or major adverse vascular events were observed during the 24-week trial period. Lactate dehydrogenase levels decreased by 83.55% from baseline at 24 weeks, with reductions seen as early as day seven. At week 24, 95% of patients had LDH levels less than or equal to1.5 times the upper limit of normal. LDH is a biomarker of intravascular hemolysis (destruction of RBCs within blood vessels) and these results show, when combined with other APPOINT results, iptacopan provided good control of intravascular hemolysis. Patients also reported clinically meaningful improvements in fatigue, with an adjusted average 10.75 point increase from baseline in Functional Assessment of Chronic Illness Therapy – Fatigue score. Iptacopan demonstrated a tolerability and safety profile consistent with previously reported data. The most commonly reported adverse events were infections, headache and diarrhea, with four serious AEs reported. No patients discontinued iptacopan in the 24-week treatment period.