
Persons with toxic gain-of-function variants in the gene encoding apolipoprotein L1 (APOL1) are at greater risk for developing rapidly progressive, proteinuric nephropathy. In preclinical studies, inaxaplin selectively inhibited APOL1 channel function in vitro and reduced proteinuria in the mouse model. Sixteen participants were enrolled in the phase 2a study. Among the 13 participants treated with inaxaplin and who met the adherence threshold, the mean change from the baseline urinary protein-to-creatinine ratio at week 13 was −47.6% (95% confidence interval, −60.0 to −31.3). Therefore, targeted inhibition of APOL1 channel function with inaxaplin reduced proteinuria in participants with two APOL1 variants and focal segmental glomerulosclerosis.
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