|
Novartis announced positive final results from APPLAUSE-IgAN, a phase III study evaluating Fabhalta (iptacopan) in adults living with IgA nephropathy (IgAN). Fabhalta, an oral alternative complement pathway inhibitor, demonstrated statistically significant, clinically meaningful superiority compared to placebo in slowing IgAN progression measured by annualized total slope of estimated glomerular filtration rate (eGFR) decline over two years.
“Progressive diseases such as IgAN present an urgent need for interventions that can ultimately improve kidney health. Many people with IgAN commonly experience fear and anxiety of disease progression,” said Ruchira Glaser, Development Unit Head, Cardiovascular, Renal & Metabolic, Novartis. “We are excited about today’s positive phase III APPLAUSE-IgAN results showing slowed eGFR decline, which add to the growing evidence of Fabhalta as a targeted therapy to preserve long-term kidney function, giving hope to people living with this condition.”?
Novartis intends to use these data to support Fabhalta submissions in 2026. Alongside Fabhalta, Novartis continues to advance its multi-asset IgAN portfolio, which also includes Vanrafia (atrasentan) and investigational compound zigakibart.
IgAN is a progressive autoimmune kidney disease with approximately 25 per million people newly diagnosed worldwide each year3. IgAN is highly debilitating as it leads to glomerular inflammation, proteinuria, and a gradual decline in eGFR. Up to 50% of patients with persistent proteinuria progress to kidney failure within 10 to 20 years of diagnosis, often requiring dialysis or kidney transplantation as part of long-term disease management. Furthermore, people living with IgAN often face mental, social, and economic challenges. Supportive care does not address the underlying causes of the disease and often fails to slow disease progression, reinforcing the need for more targeted therapies for IgAN.
In APPLAUSE-IgAN, Fabhalta was well tolerated with a favourable safety profile in line with previously reported data. Full data from the APPLAUSE-IgAN final analysis will be presented at future medical meetings.
Fabhalta (iptacopan) is an oral, Factor B inhibitor of the alternative complement pathway.
Discovered at Novartis, Fabhalta received US Food and Drug Administration (FDA) and European Commission (EC) approval in December 2023 and May 2024, respectively, for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH). Fabhalta also received accelerated approval in the US in August 2024, and in China in September 2025, for the reduction of proteinuria in adults with primary IgA nephropathy (IgAN) at risk of rapid disease progression (generally UPCR =1.5 g/g. In 2025, Fabhalta received FDA and EC approval as well as approvals in China and Japan for the treatment of adults with C3 glomerulopathy (C3G), making it the first treatment approved for this condition.
Fabhalta is being studied in a broad range of rare kidney diseases, including atypical hemolytic uremic syndrome (aHUS), immune complex membranoproliferative glomerulonephritis (IC-MPGN) and lupus nephritis (LN). Studies are ongoing to evaluate the safety and efficacy profiles in these investigational indications and support potential regulatory submissions.
APPLAUSE-IgAN (NCT04578834) is a phase III multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of twice-daily oral Fabhalta (200 mg) in 477 adult primary IgAN patients (main study population). Patients were randomized to Fabhalta or placebo, on top of supportive care (a stable dose of maximally-tolerated renin-angiotensin system (RAS) inhibitor therapy with or without a stable dose of SGLT2i).
The two primary endpoints of the study for the interim and final analysis, respectively, are proteinuria reduction at 9 months as measured by UPCR, and the annualized total eGFR slope over 24 months. During the final analysis, the following secondary endpoints were assessed: proportion of participants reaching UPCR <1 g/g without receiving corticosteroids/immunosuppressants or other newly approved drugs or initiating new background therapy for treatment of IgAN or initiating kidney replacement therapy (KRT), time from randomization to first occurrence of composite kidney failure endpoint event (reaching either sustained =30% decline in eGFR relative to baseline or sustained eGFR <15 mL/min/1.73 m2 or maintenance dialysis or receipt of kidney transplant or death from kidney failure), and change from baseline to 9 months in the fatigue scale measured by the Functional Assessment Of Chronic Illness Therapy-Fatigue questionnaire.
The main study population enrolled patients with an eGFR =30 mL/min/1.73 m2 and UPCR =1 g/g at baseline. In addition, a smaller cohort of patients with severe renal impairment (eGFR 20–30 mL/min/1.73 m2 at baseline) was also enrolled to provide additional information but not contributing to the main efficacy analyses.
??
Building on a 40-year legacy that began in transplant, Novartis is on a mission to empower breakthroughs and transform care in kidney health, starting with kidney conditions that have significant unmet need.
Historically, these conditions have had considerably less funding and research, leading to a treatment landscape largely focused on reactive or end-stage disease management, often with significant physical, emotional, and financial burdens. Our portfolio targets the underlying causes of disease, with an aim to protect kidney health and delay or prevent dialysis and/or transplantation. Our goal is to help patients get back to living life on their terms - whether at work, in school, or with loved ones, and by partnering with patients, advocates, clinicians and policymakers, we aim to raise awareness, accelerate diagnosis and get patients the right care, sooner.
|