Imagine a world where a rare and devastating kidney disease, C3 glomerulopathy (C3G), finally has a glimmer of hope. That hope arrived in March 2025 when iptacopan became the first FDA-approved therapy for C3G. But here's where it gets even more exciting: the latest data from the APPEAR-C3G extension trial reveals that this treatment doesn't just work—it keeps working, offering sustained benefits for patients over two years.
The APPEAR-C3G study (NCT04817618) was a groundbreaking phase 3 trial that pitted iptacopan against a placebo in adults with biopsy-confirmed C3G. Its goal? To assess not just efficacy but also safety and tolerability. After completing the initial 12-month trial, participants were given a choice: continue with open-label iptacopan in the extension study (NCT03955445) or step away. Of the 73 patients who finished the first year, 66 bravely opted to keep going.
At the 2025 American Society of Nephrology Kidney Week, Dr. Carla M. Nester and her team unveiled the 24-month results in a poster titled Efficacy and Safety of Iptacopan in Patients With C3 Glomerulopathy: C3G Extension Trial Interim Results From the Phase 3 APPEAR-C3G Patients. Their findings? Remarkably consistent. Patients on iptacopan saw a geometric mean reduction in their first morning urine protein-to-creatinine ratio of 35.9% at 12 months, which held steady at 34.2% by month 24. Even those who switched from placebo to iptacopan experienced significant reductions—34.0% at 12 months and 29.7% at 24 months.
But this is the part most people miss: the impact on kidney function. Before treatment, patients’ estimated glomerular filtration rate (eGFR)—a key marker of kidney health—was declining rapidly, at a rate of –7.22 mL/min/1.73 m² per year. After starting iptacopan, this decline virtually halted, stabilizing at –0.29 mL/min/1.73 m² per year over 24 months. And this is where it gets controversial: could iptacopan be not just slowing the disease but potentially altering its course?
Safety-wise, iptacopan continued to shine. No new concerns emerged, reinforcing its favorable profile. The authors concluded in their abstract, “Iptacopan demonstrated sustained reduction in proteinuria and stabilization of eGFR slope with treatment up to 24 months among APPEAR-C3G patients who rolled over to the long-term extension study. Iptacopan was well tolerated with a favorable safety profile in C3G patients.”
Funded by Novartis Pharma AG, this study marks a turning point for C3G patients. But here’s a thought-provoking question: as we celebrate these results, how do we ensure access to this life-changing therapy for all who need it? Share your thoughts in the comments—let’s keep the conversation going.
Reference:
2025 American Society of Nephrology Kidney Week. Abstract No. FR-PO0838. doi:10.1681/ASN.202599z9n79j (https://journals.lww.com/jasn/fulltext/2025/10001/efficacyandsafetyofiptacopaninpatients_with.2259.aspx)
