New Novartis data at ERA 2026 advance scientific understanding of kidney disease and reinforce portfolio strength

Novartis Unveils Key Kidney Disease Data at ERA 2026

Novartis is set to present 15 abstracts from its kidney portfolio at the European Renal Association (ERA) Congress in Glasgow from June 3-6, 2026. The presentations will include late-breaking Phase III results for Vanrafia (atrasentan) from the ALIGN trial and Fabhalta (iptacopan) from the APPLAUSE-IgAN study, both focusing on IgA nephropathy (IgAN). Additionally, extended 124-week follow-up data for the investigational anti-APRIL therapy zigakibart in IgAN will be featured, alongside new insights into disease characteristics in IgAN and C3 glomerulopathy (C3G). These findings aim to advance scientific understanding and evolve kidney care.

• Final data from the APPLAUSE-IgAN study for Fabhalta (iptacopan) will be presented, demonstrating that the drug achieves near-normal kidney function decline in prespecified IgA nephropathy patient subgroups. This late-breaker oral presentation underscores iptacopan's potential in managing this progressive immune-mediated kidney disease, offering a significant advancement in treatment approaches for patients.
• The ALIGN trial will feature 2.5-year eGFR results for Vanrafia (atrasentan) in participants with IgA nephropathy. This late-breaker oral presentation will provide crucial long-term efficacy and safety data, reinforcing atrasentan's role in protecting kidney health and potentially delaying or preventing the need for dialysis or transplantation in patients with IgAN.
• New data will be presented on the efficacy and safety outcomes after 124 weeks of zigakibart treatment in IgA nephropathy. As an investigational anti-APRIL therapy, these extended follow-up results are vital for understanding the sustained benefits and safety profile of zigakibart, contributing to the evolving landscape of IgAN therapies and future research directions.

Addressing Unmet Needs in IgA Nephropathy with New Data

Recent research has identified significant gaps in IgA nephropathy management, particularly in clinical trial design and patient population coverage. These unmet needs are driving targeted research efforts to address previously understudied patient groups and therapeutic challenges.

• Systematically excluded clinical presentations from randomized controlled trials include rapidly progressive forms, malignant hypertension, thrombotic microangiopathy, and nephrotic syndrome, with most RCTs focusing only on patients with refractory non-nephrotic proteinuria and preserved renal function

• Special populations requiring attention encompass pregnant patients and transplant recipients, along with better understanding of hematuria impact management, representing critical gaps in evidence-based care

• High-risk patient identification and stratification remains essential due to clinical heterogeneity resulting in divergent renal outcomes, with need for early identification of patients at greatest risk of kidney failure as primary focus for clinical trials

• Dynamic disease monitoring limitations stem from classical prognostic models that rely on static baseline parameters and may not adequately reflect disease trajectories, limiting utility in real-time clinical management

• Therapeutic personalization challenges include determining optimal combination therapies for individuals, with no definitive therapeutic regimens currently existing to treat or prevent disease progression

• Biomarker-guided therapy development focuses on non-invasive biomarkers for patient stratification and integrated diagnostic-therapeutic frameworks, though clinical translation remains challenging

• Trial design improvements target age-inclusive approaches with systemic disease secondary endpoints and patient-reported outcomes, addressing greater spontaneous improvement in children and worse kidney outcomes in specific populations

Late-Breaking Phase III Outcomes for Vanrafia and Fabhalta in IgAN

Recent clinical trials have demonstrated significant advances in IgA nephropathy treatment across multiple therapeutic targets. These studies encompass novel complement inhibitors, APRIL antagonists, and established agents in new clinical contexts, providing comprehensive safety and efficacy data for emerging therapeutic strategies.

Expanding Fabhalta's Reach Beyond IgAN to C3 Glomerulopathy

Iptacopan has demonstrated therapeutic potential across multiple complement-mediated disorders beyond IgA nephropathy, with the most advanced development occurring in paroxysmal nocturnal haemoglobinuria (PNH), where it received FDA approval in December 2023. The PNH clinical program included two pivotal phase 3 trials with distinct intervention models. The APPLY-PNH trial employed an open-label, randomised design across 39 centres, where patients were assigned in an 8:5 ratio to either receive oral iptacopan 200 mg twice daily or continue their existing intravenous anti-C5 therapy (eculizumab or ravulizumab) for 24 weeks, followed by a 24-week extension where all patients received iptacopan monotherapy. The complementary APPOINT-PNH trial utilized a single-arm design in complement inhibitor-naive patients, with all participants receiving iptacopan 200 mg twice daily for 24 weeks followed by an extension period.

The most significant expansion opportunity lies in complement 3 glomerulopathy (C3G), where the phase 3 APPEAR-C3G trial represents a rigorous randomised, double-blind, placebo-controlled study design. This trial enrolls 68 adults with biopsy-confirmed C3G and employs a 1:1 randomisation to iptacopan 200 mg twice daily versus placebo for six months, followed by open-label iptacopan treatment for all participants for an additional six months. The primary objective focuses on proteinuria reduction measured by 24-hour urine protein-creatinine ratio, with key secondary endpoints including kidney function assessed by estimated glomerular filtration rate, histological disease activity scores, and fatigue measures. All participants receive maximally tolerated ACE inhibitor or ARB therapy and vaccination against encapsulated bacteria as standard care.

Additional indications under investigation include immune thrombocytopenia (ITP), where iptacopan is progressing through phase 2 or 3 studies specifically targeting heavily pretreated and refractory patient populations. The complement factor B inhibition mechanism offers a novel therapeutic approach distinct from existing approved agents such as thrombopoietin receptor agonists and fostamatinib. Case reports have also documented successful treatment outcomes in primary immune complex-mediated membranoproliferative glomerulonephritis, with patients achieving significant proteinuria reduction and sustained remission when used as monotherapy after conventional immunosuppressive therapies failed. These diverse applications highlight iptacopan's potential as a broad-spectrum complement inhibitor across multiple rare disease indications.

A New Era for IgA Nephropathy and C3G Treatment

The upcoming European Renal Association (ERA) Congress is poised to be a landmark event for nephrology, particularly concerning IgA nephropathy (IgAN) and C3 glomerulopathy (C3G). Novartis's presentation of late-breaking Phase III data for atrasentan and iptacopan, alongside extended follow-up for zigakibart, signals a significant acceleration in targeted therapies for these debilitating kidney diseases.

IgAN, the most common primary glomerular disease, carries a substantial risk of progression to end-stage kidney disease. Historically, treatments were largely supportive or involved broad immunosuppression with considerable side effects. Atrasentan's ALIGN trial data, demonstrating a clinically meaningful reduction in proteinuria, offers a promising new avenue. As a selective endothelin A receptor antagonist, it targets a key pathway in kidney injury. While previous ERAs faced fluid retention challenges, particularly in diabetic populations, its application in IgAN may present a different risk-benefit profile.

Iptacopan, an oral complement factor B inhibitor, already has accelerated approval for IgAN. The APPLAUSE-IgAN Phase III results are expected to reinforce its efficacy in reducing proteinuria with a favorable safety profile. Its mechanism, targeting the alternative complement pathway, addresses a fundamental driver of IgAN pathogenesis and shows promise in C3G. The emergence of such targeted complement inhibitors, alongside anti-APRIL therapies like zigakibart, which aims to reduce pathogenic IgA1 production, underscores a paradigm shift towards precision medicine in IgAN. The 124-week follow-up data for zigakibart will be crucial for understanding the long-term durability and safety of this novel approach.

However, this progress faces considerations. The competitive IgAN landscape is rapidly intensifying, demanding clear differentiation for each new agent. While targeted therapies offer improved specificity, the long-term safety and optimal duration of treatment for novel mechanisms require ongoing evaluation. Potential rare or delayed adverse events will influence clinical adoption. Ultimately, these presentations will provide critical insights into how these innovative treatments can be integrated into a new, multi-faceted approach to preserve kidney function and improve outcomes for patients with IgAN and C3G.