C3G Breakthroughs: First FDA-Approved Targeted Therapies Redefine Care

C3 glomerulopathy (C3G) has historically been challenging to manage, often leading to severe proteinuria, progressive kidney function loss, and kidney failure. Many patients, frequently diagnosed in adolescence or early adulthood, faced the prospect of dialysis or transplant, with high rates of disease recurrence. Previously, treatment relied on off-label, nonspecific immunosuppressants, lacking disease-specific evidence and carrying risks like infection and cancer associated with high doses.

A dramatic shift has occurred with the recent US Food and Drug Administration (FDA) approvals of two targeted C3G therapies: iptacopan (Fabhalta) and pegcetacoplan (Empaveli). Iptacopan, an oral factor B inhibitor, was approved in March 2025, followed by pegcetacoplan, a complement C3 inhibitor, approved for adults and adolescents. These approvals are a pivotal moment, offering targeted mechanisms addressing underlying complement dysregulation. Both are backed by trial data showing meaningful reductions in proteinuria and markers of disease activity.

The availability of both an oral (iptacopan) and a subcutaneous (pegcetacoplan) option enables a more personalized approach. Pegcetacoplan’s approval for adolescents and post-transplant patients offers advantages for younger individuals and those with complex histories, while iptacopan provides ease of use. This allows for shared decision-making between clinicians and patients, considering efficacy, safety, age, comorbidities, and preferences. These new treatments represent a "game changer" for patients, offering the potential to treat the disease upfront and potentially halt its progression.

While a breakthrough, these approvals also bring responsibilities. Providers must stay current with evolving data, monitor long-term safety, and understand patient characteristics predicting response. Real-world experience will be crucial in refining strategies, especially as new therapies emerge and combination treatments are explored. Experts anticipate updates to clinical guidelines, which will facilitate a more appropriate and widely adopted approach to C3G management.