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

 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

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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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