Gerald Appel, MD, is a professor of clinical medicine, director of clinical nephrology, and director of the Glomerular Disease Center at Columbia University.

Gerald Appel, MD

Rare Disease Day 2026: Kidney Diseases Enter Optimistic Therapeutic Era

On Rare Disease Day 2026, 4 clinicians share their insights and perspectives on the groundbreaking improvements in the rapidly evolving field of rare kidney diseases.

Despite persistent awareness gaps in rare kidney disease care, a wave of FDA approvals and phase 3 trial successes in 

 alongside updated 2025 KDIGO Practice Guidelines, has fueled growing clinician optimism about a rapidly advancing, disease-modifying treatment era.

Rare kidney diseases remain complex and underrecognized, leaving both patients and clinicians with challenges in early diagnosis, risk stratification, and long-term management. Yet recent scientific advances and regulatory approvals are beginning to reshape the therapeutic landscape.

Momentum in rare kidney disease care has accelerated with multiple FDA approvals supported by pivotal clinical trial data. In IgAN, 

demonstrated significant reductions in proteinuria and preservation of kidney function in the NefIgArd trial, while 

, a dual endothelin-angiotensin receptor antagonist, showed positive outcomes in the PROTECT study. The addition of 

, an endothelin A receptor antagonist, further underscores the diversification of therapeutic strategies in IgAN, with the ALIGN Phase III trial demonstrating clinically meaningful reductions in proteinuria, a key surrogate for slowing disease progression. Iptacopan, a factor B inhibitor targeting the alternative complement pathway, reported encouraging efficacy in the APPLAUSE-IgAN trial, highlighting a precision-based approach to treatment.

In C3G, iptacopan also showed promising results in the 

, alongside other complement-targeted therapies such as 

 and danicopan, reflecting growing opportunities for disease modification in a previously limited treatment space.

These advances are complemented by the updated 

, which provide evidence-based recommendations to support clinicians in diagnosis, monitoring, and treatment selection, fostering a more standardized and patient-centered approach.

Together, these therapies, spanning endothelin-angiotensin signaling modulation, complement inhibition, and targeted anti-inflammatory strategies, illustrate a shift toward precision medicine in rare kidney disease. 

Editor's Note: Norouzi reports relevant disclosures with Calliditas, Travere, Apellis, and others. Appel reports relevant disclosures with Novartis, Travere Therapeutics, and others. Russo reports no relevant disclosures. Arora declares no relevant disclosures.Reference

6 New Kidney Disease Medications Approved in 2025. National Kidney Foundation. Published January 21, 2026. 

https://www.kidney.org/news-stories/6-new-kidney-disease-medications-approved-2025

Sayna Norouzi, MD, Cheung K, Skolnik E, Peleg Y. 2025 KDIGO Guideline Update for IgAN. Hcplive.com. Published January 14, 2026. Accessed February 28, 2026. https://www.hcplive.com/view/2025-kdigo-guideline-update-for-igan

Perkovic V, Barratt J, Rovin BH, et al; APPLAUSE‑IgAN Investigators. 

Alternative complement pathway inhibition with iptacopan in IgA nephropathy.

 N Engl J Med. 2025;392(6):531‑543. doi:10.1056/NEJMoa2410316. Published online 2024 Oct 25.

Kavanagh D, Bomback AS, Vivarelli M, et al. 

Oral iptacopan therapy in patients with C3 glomerulopathy: a randomized, double‑blind, placebo‑controlled, phase 3 study.

 Lancet. 2025;406(10512):1587‑1598. doi:10.1016/S0140‑6736(25)01148‑1.

Lafayette R, et al; NefIgArd Investigators. 

Efficacy and safety of a targeted‑release formulation of budesonide in patients with primary IgA nephropathy (NefIgArd): 2‑year results from a randomized phase 3 trial.

KDIGO IgAN and IgA Vasculitis Work Group; Rovin BH, Barratt J, Cook HT, et al. 

KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV).

 Kidney Int. 2025;108(4S):S1‑S71. doi:10.1016/j.kint.2025.04.004.

Novartis receives FDA accelerated approval for Fabhalta (iptacopan), the first and only complement inhibitor for reduction of proteinuria in adults with primary IgA nephropathy.

Novartis investigational atrasentan Phase III study demonstrates clinically meaningful proteinuria reduction in patients with IgA nephropathy (ALIGN).

Videos

On Rare Disease Day 2026, clinicians share their perspective on the evolving landscape for IgAN and C3G. 

 has been a disease without a targeted treatment, leaving patients and clinicians to deal with a devastating disease course with no clear standard of care.

Caused by dysregulation of the alternative complement pathway, C3G often leads to progressive kidney failure, with many patients ultimately requiring transplantation—only to see the disease recur.

The US Food and Drug Administration approval of Novartis’ oral iptacopan (Fabhalta) for the treatment of adults with C3 glomerulopathy (C3G) marks a turning point in C3G care, offering the first FDA-approved drug for patients with the ultra-rare kidney disease.

The decision was based on data from the phase 3 APPEAR-C3G trial, where iptacopan met the primary endpoint of reducing 24-hour urine protein-to-creatinine ratio (UPCR) by 35.1% (95% CI, 13.8% to 51.1%; 

 = .0014), with sustained reductions at 12 months.

Additional analyses revealed use of iptacopan was associated with a higher proportion of patients meeting the composite renal endpoint—defined as a ≥50% UPCR reduction and ≤15% eGFR decline—occurring in 43.5% of iptacopan-treated patients versus 25.0% of those who switched from placebo at 6 months. A favorable effect on eGFR trajectory was also observed relative to historical trends.

Not only does this approval provide C3G patients with a treatment specifically designed to address the root cause of their disease, but it also opens the door for further advancements in complement-targeted therapies. With a new tool in their arsenal, clinicians can now offer patients a chance to slow or even stop disease progression—something that was once out of reach.

For additional insight into the significance of the approval and its impact on C3G care, the editorial team of 

 spoke with Gerald Appel, MD, a professor of clinical medicine, director of clinical nephrology, and director of the Glomerular Disease Center at Columbia University; Andrew Bomback, MD, an assistant professor of medicine at Columbia University Medical Center; and Jared Hassler, MD, a pathologist at the Temple University Hospital.

Expert Perspectives: Iptacopan FDA Approval for C3 Glomerulopathy

Relevant disclosures for Appel include Aurinia, Bristol Myers Squibb, Genentech, Genzyme-Sanofi, Eli Lilly, Merck, Pfizer, Mallinckrodt, Achillion, Alexion, Reata, Travere Therapeutics, GlaxoSmithKline, Vertex Therapeutics, Novartis, Apellis, Chinook, Arrowhead, Calliditas, and Vera. Relevant disclosures for Bomback include Amgen, Novartis, Kezar, Silence Therapeutics, Genentech, Visterra, Catalyst, Q32, and Apellis. Relevant disclosures for Hassler include Travere Therapeutics, Omeros, and Novartis.

Campbell P. FDA Approves Oral Iptacopan (Fabhalta) as First C3 Glomerulopathy Therapy. HCPLive. March 20, 2025. Accessed March 21, 2025. 

https://www.hcplive.com/view/fda-approves-oral-iptacopan-fabhalta-as-first-c3-glomerulopathy-therapy

A trio of nephrology experts discuss the significance of iptacopan’s FDA approval as the first treatment for C3G.

Gerald Appel, MD

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