Results From Clinical Trial of Iptacopan in C3G

Carla Nester, MD, University of Iowa Stead Family Children’s Hospital, discusses results from the clinical trial of iptacopan in complement 3 glomerulopathy (C3G).

C3G is a rare kidney disease characterized by damage to kidney glomeruli due to abnormal activation of the complement system. When C3 proteins get lodged in the kidney, glomeruli get injured and buildup of toxins and reduced urine production occur. This can ultimately lead to declined kidney function. Common signs and symptoms include:

- Hematuria
- Proteinuria
- Reduced glomerular filtration rate and increased creatinine levels
- Fatigue
- Edema of the hands, feet, and ankles

Currently, the FDA has not approved any treatments for C3G. Management focuses on slowing the progression of kidney damage and addressing symptoms.

Iptacopan is an orally administered targeted factor B inhibitor of the alternative complement pathway. It is currently approved by the U.S. Food and Drug Administration for primary immunoglobulin A nephropathy (IgAN), a rare kidney disorder that occurs when IgA, a protein that helps the body fight infections, settles in the kidneys. The treatment has illustrated the ability to reduce proteinuria.

APPEAR-C3G is a phase 3, multicenter, randomized, double-blind, parallel group, placebo-controlled study evaluating the efficacy and safety of twice daily iptacopan in patients with C3G. The primary endpoint was reduction from baseline of proteinuria at 6 months. This endpoint was met with a statistically significant 35.1% reduction in proteinuria versus placebo on top of supportive care at 6 months.

Additionally, long-term data has demonstrated sustained results with iptacopan with supportive care at the one year mark. Improvements have also been observed in estimated glomerular filtration rate (eGFR) slope. Iptacopan has shown a favorable safety profile with no new safety signals.