Phase 2b AMPLIFIED study of inaxaplin in people with APOL1-mediated kidney disease (AMKD) and modest proteinuria and in people with AMKD and type 2 diabetes.

In this study, inaxaplin was evaluated as a 45 mg once-daily dose on top of optimized standard of care. Forty-one people were enrolled and dosed in two cohorts: 1) people with AMKD with modest proteinuria (UACR ≥0.1 g/g to <0.42 g/g) were eligible for cohort 1 (N=23), and 2) people with AMKD, type 2 diabetes and proteinuria (UACR ≥0.1 g/g to <6 g/g) were eligible for cohort 2 (N=18). The primary endpoint in the study was mean percent change in UACR at Week 13 compared to baseline, evaluated separately for each cohort. The other endpoints included mean percent change in urine protein to creatinine ratio (UPCR) at Week 13 compared to baseline and safety.

In cohort 1, treatment with inaxaplin administered on top of optimized standard of care led to a reduction of -42.7% (95% CI -58.3%, -21.1%) in UACR at Week 13 compared to baseline. UPCR decreased by -44.7% from baseline at Week 13. These results are in line with the treatment effect previously reported in the Phase 2a study of inaxaplin in AMKD with focal segmental glomerulosclerosis (FSGS), which demonstrated a reduction in UACR of -43.4% and a reduction in UPCR of -47.6% at Week 13 compared to baseline. In this modest proteinuria cohort, most people were not diagnosed with FSGS.

In cohort 2, treatment with inaxaplin administered on top of optimized standard of care led to a reduction in UACR at Week 13 of -17.3% (95% CI -36.3%, 7.2%) compared to baseline. UPCR decreased by -25.4% from baseline at Week 13.