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The following is a summary of “Alternative Complement Pathway Inhibition with Iptacopan in IgA Nephropathy,” published in the October 2024 issue of New England Journal of Medicine by Perkovic et al.
Researchers conducted a retrospective study on IgA nephropathy, where the alternative complement pathway plays a key role. Iptacopan binds to factor B and inhibits this pathway.
They conducted a phase 3, double-blind, randomized, placebo-controlled trial enrolling adults with biopsy-confirmed IgA nephropathy and proteinuria (24-hour urinary protein-to-creatinine ratio ≥1 g) despite optimized supportive therapy. They randomly assigned patients (1:1) to receive oral iptacopan (200 mg) or placebo twice daily for 24 months with supportive therapy. The primary endpoint was the change in the 24-hour urinary protein-to-creatinine ratio in month 9. A secondary endpoint was the proportion of patients with a ratio <1 at month 9 without rescue therapy, alternative medication, or kidney-replacement therapy. Safety was assessed, and kidney function will be evaluated in 2 years.
The results showed that among 222 patients in the iptacopan group and 221 in the placebo group, the interim efficacy analysis included 250 patients (125 per group) who remained or discontinued by month 9. At month 9, the adjusted geometric mean 24-hour urinary protein-to-creatinine ratio was 38.3% lower with iptacopan than with placebo (95% CI, 26.0–48.6; P<0.001). Secondary endpoint analyses supported this reduction. Safety findings were consistent, with similar adverse event rates in both groups, mostly mild to moderate and reversible. No increased risk of infection was observed.
Investigators found that iptacopan significantly reduced proteinuria in patients with IgA nephropathy compared with placebo.
Source: nejm.org/doi/full/10.1056/NEJMoa2410316
