Vertex reports encouraging Phase IIb AMPLIFIED results for inaxaplin in APOL1‑mediated kidney disease. The modest‑proteinuria cohort (n=23) saw a 42.7% reduction in UACR and a 44.7% reduction in UPCR at week 13; the T2D cohort (n=18) experienced smaller reductions. Inaxaplin was generally well tolerated with no treatment‑related serious adverse events. Vertex has completed enrolment in the Phase II/III AMPLITUDE study and expects an interim readout in early 2027 that could support accelerated US approval.
Vertex’s Inaxaplin Shows Strong Phase IIb Efficacy in APOL1‑Mediated Kidney Disease; AMPLITUDE Interim Readout Expected in 2027
AMKD is caused by two APOL1 gene variants and can lead to progressive kidney damage. Credit: sasirin pamai / Shutterstock.com.
Vertex Pharmaceuticals has reported positive topline results from the Phase IIb AMPLIFIED trial of inaxaplin in people with APOL1‑mediated kidney disease (AMKD), including cohorts with modest proteinuria and with type 2 diabetes (T2D). The once‑daily 45 mg dose of inaxaplin was administered on top of optimised standard of care.
The AMPLIFIED study enrolled 41 participants across two cohorts: 23 people with AMKD and modest proteinuria, and 18 people with AMKD, T2D and proteinuria. Outcomes were measured at week 13.
Efficacy Results
Modest‑Proteinuria Cohort (n=23): At week 13, urine albumin‑to‑creatinine ratio (UACR) declined by 42.7% versus baseline (95% CI: -58.3% to -21.1%). Urine protein‑to‑creatinine ratio (UPCR) fell by 44.7%. Most participants in this cohort had not been diagnosed with focal segmental glomerulosclerosis (FSGS).
T2D Cohort (n=18): At week 13, UACR declined by 17.3% from baseline (95% CI: -36.3% to 7.2%) and UPCR decreased by 25.4%. Vertex described this as a smaller, but clinically meaningful, effect compared with the modest‑proteinuria cohort.
Vertex noted that the reductions seen in the modest‑proteinuria cohort are consistent with prior Phase IIa findings in patients with AMKD and FSGS, which showed UACR and UPCR reductions of 43.4% and 47.6%, respectively, at week 13.
Safety
Inaxaplin was generally well tolerated across both cohorts. No serious adverse events (SAEs) were considered related to treatment, and all reported adverse events (AEs) were mild or moderate. The most common AE was headache (7.3% of participants). Five participants experienced isolated, asymptomatic transaminase elevations that resolved without sequelae.
Carmen Bozic, Chief Medical Officer and EVP of Global Medicines Development and Medical Affairs at Vertex, said the data bolster the case for inaxaplin as a targeted, potentially first‑and‑best‑in‑class therapy for AMKD and highlighted Vertex’s intent to discuss these findings with regulators alongside the AMPLITUDE pivotal study.
Regulatory Pathway and Next Steps
Vertex has completed full enrolment in the Phase II/III AMPLITUDE trial, which is evaluating inaxaplin in a separate cohort with severe proteinuria and no other kidney disease causes. The company expects an interim analysis readout in early 2027 after the relevant cohort has reached 48 weeks of treatment. If positive, those data could support a potential accelerated approval filing in the United States.
About AMKD: APOL1‑mediated kidney disease is driven by two risk variants in the APOL1 gene and can cause progressive kidney damage and proteinuria.
Additional Vertex News: In June 2025, Vertex reported data from the Phase I/II portion of FORWARD‑101 evaluating zimislecel (VX‑880), a stem cell‑derived islet cell therapy for type 1 diabetes.
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