Iptacopan Reduces Proteinuria and Stabilizes Kidney Function in C3 Glomerulopathy.
In a phase 2 extension study of 26 adults with C3 glomerulopathy, 12 months of open-label iptacopan cut 24-hour proteinuria by 57% and improved eGFR in native-kidney patients, while transplant recipients with recurrent disease maintained stable kidney function.
Background
C3 glomerulopathy (C3G) is a chronic, ultra-rare, progressive primary glomerulonephritis caused by overactivation of the alternative complement pathway. It leads to kidney failure in most patients and recurs frequently after transplantation. Iptacopan (LNP023) is an oral, proximal complement inhibitor that specifically targets factor B to selectively inhibit the alternative pathway.
Study design
This was a phase 2 extension study of 26 adult patients receiving open-label iptacopan. Cohort A comprised patients with native-kidney C3G; cohort B comprised patients with recurrent C3G after kidney transplantation. Outcomes were assessed at 12 months and included 24-hour urine protein-to-creatinine ratio (UPCR), estimated glomerular filtration rate (eGFR), serum C3, and C3 deposit score on renal biopsy.
Key findings
At 12 months, cohort A showed a 57% reduction in 24-hour UPCR (P < 0.0001; CI 0.31-0.59), an eGFR improvement of 6.83 ml/min per 1.73 m2 (P = 0.0174; CI 1.25-12.40), and a rise in serum C3 (geometric mean ratio to baseline 3.53; P < 0.0001; CI 3.01-4.15). Cohort B patients mostly had normal baseline urinary protein excretion (mean 24-hour UPCR 121, range 9-445), which fell by a non-significant 21% (CI 0.48-1.31; P = 0.3151); mean eGFR remained at baseline values (change -0.96 ml/min per 1.73 m2; P = 0.7335; CI -6.60 to 4.69), while serum C3 rose significantly (ratio 1.96; CI 1.70-2.27; P < 0.0001). Across cohorts A and B combined, the median change in biopsy C3 deposit score was -7.00 (CI -12.00 to 4.00) at 9 to 12 months of treatment.
Clinical implications
The authors conclude that these data provide a clinical rationale for further evaluation of long-term iptacopan treatment in C3 glomerulopathy. The proteinuria and eGFR gains were confined to the native-kidney cohort; in the post-transplant recurrent-disease cohort the proteinuria and eGFR changes were not statistically significant, with the consistent signal across both groups being restoration of serum C3.
Category
Transplant
Source
Kidney Int Rep
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