APPLAUSE-IgAN: Iptacopan (Fabhalta) Meets eGFR Decline Primary Endpoint

Novartis has announced positive final results from the phase 3 APPLAUSE-IgAN study of iptacopan (Fabhalta) in adults with IgA nephropathy (IgAN).1

As described in an October 16, 2025, press release from the Company, the 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 2 years. Of note, Novartis described plans to use these data to support regulatory submissions for iptacopan in 2026.1

“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,” Ruchira Glaser, Development Unit Head, Cardiovascular, Renal & Metabolic, Novartis, said in a statement.1 “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.”

Iptacopan received US Food and Drug Administration (FDA) approval in December 2023 for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH), later receiving accelerated approval in August 2024 for the reduction of proteinuria in adults with primary IgAN at risk of rapid disease progression. Most recently, in 2025, iptacopan received FDA approval for the treatment of adults with C3 glomerulopathy (C3G), making it the first treatment approved for this ultra-rare kidney disease.2,3

The oral alternative complement pathway inhibitor is also being studied in atypical hemolytic uremic syndrome, immune complex membranoproliferative glomerulonephritis, and lupus nephritis, with ongoing studies evaluating the safety and efficacy profiles in these investigational indications to support potential regulatory submissions.1

APPLAUSE-IgAN is a phase 3 multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of twice-daily oral iptacopan 200 mg in 477 adults with primary IgAN. Patients were randomly assigned to iptacopan or placebo, in addition to supportive care, defined as a stable dose of maximally-tolerated renin-angiotensin system inhibitor therapy with or without a stable dose of SGLT2i.1

The 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
• 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)
• 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, defined as 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.1

As described by Novartis, in APPLAUSE-IgAN, iptacopan was well tolerated with a favorable safety profile in line with previously reported data. The Company plans to present data from the APPLAUSE-IgAN final analysis at future medical meetings.1

References

1. Novartis. Novartis Fabhalta® (iptacopan) meets Phase III primary endpoint, slows kidney function decline in patients with IgA nephropathy (IgAN). October 16, 2025. Accessed October 16, 2025. https://www.novartis.com/news/media-releases/novartis-fabhalta-iptacopan-meets-phase-iii-primary-endpoint-slows-kidney-function-decline-patients-iga-nephropathy-igan

2. Campbell P. Iptacopan Receives Accelerated Approval for Reducing Proteinuria in IgA Nephropathy. HCPLive. August 8, 2024. Accessed October 16, 2025. https://www.hcplive.com/view/iptacopan-receives-accelerated-approval-for-reducing-proteinuria-in-iga-nephropathy

3. Campbell P. FDA Approves Oral Iptacopan (Fabhalta) as First C3 Glomerulopathy Therapy. HCPLive. March 20, 2025. Accessed October 16, 2025. https://www.hcplive.com/view/fda-approves-oral-iptacopan-fabhalta-as-first-c3-glomerulopathy-therapy