Novartis’ Fabhalta® Delivers Sustained Efficacy And Safety In PNH Patients Switching from Anti-C5 Therapies

Novartis has announced encouraging results from its Phase IIIB APPULSE-PNH study evaluating Fabhalta® (iptacopan), a first-in-class, oral factor B inhibitor, in adults with paroxysmal nocturnal hemoglobinuria (PNH) who switched from existing anti-C5 therapies. In patients with baseline hemoglobin (Hb) ≥10 g/dL, Fabhalta delivered a mean Hb increase of 2.01 g/dL over 24 weeks, with nearly all patients achieving normal or near-normal Hb levels. 

“Today, some patients living with PNH have unmet needs not addressed by eculizumab or ravulizumab. The positive results from APPULSE-PNH reinforce that Fabhalta can provide clinically meaningful improvements in hemoglobin among patients with higher baseline hemoglobin levels than those enrolled in previous trials, while offering an oral monotherapy for patients,” said Austin Kulasekararaj, Consultant Hematologist, Kings College Hospital and Kings College London. 

Crucially, no patients required blood transfusions during the study period. In addition, 92.7% of patients achieved Hb ≥12 g/dL, a benchmark associated with normalized red blood cell counts. Patients also experienced significant fatigue reduction, with FACIT-Fatigue scores approaching those seen in the general population, marking a meaningful improvement in quality of life alongside clinical efficacy.

“Novartis is dedicated to advancing research and innovation that can transform care and significantly improve the lives of people living with PNH and those who support them. New data from APPULSE-PNH, combined with findings from the Phase III roll-over extension of the APPLY-PNH and APPOINT-PNH studies, reinforce the efficacy and safety profile of Fabhalta in delivering real benefits to patients. Fabhalta is the first and only oral monotherapy currently available for the treatment of adults with PNH, regardless of previous treatment experience,” said Shreeram Aradhye, M.D., President, Development and Chief Medical Officer, Novartis. 

Fabhalta maintained control of intravascular hemolysis and helped resolve extravascular hemolysis, evidenced by stabilized lactate dehydrogenase and reduced reticulocyte counts. These findings are reinforced by long-term data from patients in previous pivotal Phase III trials (APPLY-PNH and APPOINT-PNH) and their rollover extensions, which show Fabhalta remains well-tolerated with no new safety signals, supporting its potential as a new oral standard of care for patients with PNH.