BASEL, Oct. 16, 2025 — Novartis announced positive final Phase III results from its APPLAUSE-IgAN trial, confirming that Fabhalta® (iptacopan), an oral alternative complement pathway inhibitor, significantly slowed kidney function decline versus placebo in adults with IgA nephropathy (IgAN). Over two years, Fabhalta delivered clinically meaningful improvement in eGFR slope, a key marker of kidney function, establishing its potential as the first and only complement inhibitor to delay IgAN progression.
Science Significance
Fabhalta achieved statistically significant and clinically meaningful benefits in preserving kidney function.
In the APPLAUSE-IgAN final analysis, patients treated with Fabhalta 200 mg twice daily showed a significant improvement in the annualized total eGFR slope compared with placebo, demonstrating a slower decline in kidney function over 24 months. The study enrolled 477 adult patients with primary IgAN already on maximally tolerated renin-angiotensin system inhibitors, with or without SGLT2 inhibitors, representing a real-world treatment scenario. eGFR (estimated glomerular filtration rate) is the key indicator of renal performance, and its preservation directly correlates with delayed onset of kidney failure.
“These data reinforce Fabhalta’s role as a targeted oral therapy that preserves long-term kidney function and offers hope to patients with IgAN,” said Ruchira Glaser, Development Unit Head, Cardiovascular, Renal & Metabolic at Novartis.
Regulatory Significance
Fabhalta received U.S. FDA accelerated approval in 2024 for reducing proteinuria in adults with IgAN, based on interim APPLAUSE data. The newly released final analysis provides confirmatory evidence for a traditional approval submission planned in 2026. The findings further strengthen Fabhalta’s regulatory foundation following its 2023 FDA and 2024 EC approvals for paroxysmal nocturnal hemoglobinuria (PNH), and subsequent 2025 approvals for C3 glomerulopathy (C3G) in the U.S., Europe, China, and Japan. Fabhalta is currently the only approved complement inhibitor for adults with IgAN, positioning Novartis as a regulatory leader in complement-mediated kidney disorders.
Full APPLAUSE-IgAN data will be presented at upcoming medical congresses and submitted for publication in a peer-reviewed journal.
Business Significance
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The successful completion of APPLAUSE-IgAN marks a strategic milestone in Novartis’s growing renal portfolio, reinforcing its 40-year legacy in nephrology. Fabhalta’s performance solidifies its commercial trajectory as a next-generation, oral complement inhibitor, expanding beyond PNH into chronic kidney disease indications. The positive readout also bolsters confidence in Novartis’s multi-asset kidney pipeline, which includes Vanrafia® (atrasentan) and zigakibart, an investigational antibody for IgAN and other glomerular diseases. Analysts project that Fabhalta could exceed $3 billion in annual revenue by 2030, supported by its oral dosing convenience, broad complement-pathway applicability, and continued expansion into rare kidney diseases such as aHUS, IC-MPGN, and lupus nephritis. “These results validate our complement strategy and support Fabhalta as a cornerstone of our renal portfolio,” Novartis said in a company statement.
Patients’ Significance
IgA nephropathy is a progressive autoimmune kidney disease, affecting an estimated 25 new cases per million people annually. It often leads to glomerular inflammation, proteinuria, and gradual loss of eGFR, with up to 50% of patients progressing to kidney failure within 10–20 years. Fabhalta offers a meaningful new option for patients whose disease progresses despite supportive therapy. By directly targeting Factor B in the alternative complement pathway, Fabhalta intervenes upstream in disease biology, slowing inflammation and glomerular damage that drive kidney decline. Beyond clinical benefits, the oral route of administration improves patient experience by removing infusion burdens common with biologic complement inhibitors. Patients may now maintain work, study, and social activities without hospital-based treatment interruptions — a significant quality-of-life gain.
Policy Significance
The results have broad implications for health policy and renal care access. Oral complement inhibition could shift the treatment paradigm toward early, outpatient-based intervention, potentially reducing long-term costs of dialysis and transplantation. As the first-in-class oral Factor B inhibitor, Fabhalta aligns with global kidney-health strategies such as the KDIGO Guidelines and the World Health Organization’s Non-Communicable Disease Agenda, emphasizing early detection and targeted disease-modifying therapies. Health economists anticipate that delaying dialysis by even two years could yield substantial savings for healthcare systems while improving patient outcomes. Fabhalta’s real-world accessibility and tolerability profile may also influence reimbursement frameworks and treatment guidelines worldwide.
Transaction Highlights
In the APPLAUSE-IgAN Phase III study, 477 adult patients were randomized to receive either Fabhalta or placebo on top of standard-of-care therapies, including renin-angiotensin system inhibitors and SGLT2 inhibitors. The primary endpoint, annualized eGFR slope over 24 months, demonstrated significant improvement in the Fabhalta group, confirming superiority over placebo in slowing disease progression. Secondary outcomes included reductions in proteinuria, delay in composite kidney failure events, and improved fatigue scores measured by the Functional Assessment of Chronic Illness Therapy–Fatigue questionnaire. The drug was well tolerated, with safety findings consistent with prior data and no new safety signals observed. Novartis plans to submit these results to global regulators in 2026 to transition Fabhalta’s accelerated approval to a full approval and broaden its indications. Beyond IgAN, Fabhalta is being studied across multiple rare renal diseases—including C3 glomerulopathy, atypical hemolytic uremic syndrome, immune complex membranoproliferative glomerulonephritis, and lupus nephritis—as part of Novartis’s long-term kidney disease innovation strategy.
Source: Novartis Press Release
