Boston — Vertex Pharmaceuticals Incorporated said its Phase 2b AMPLIFIED study of inaxaplin showed reductions in proteinuria in two additional groups of people with APOL1-mediated kidney disease, or AMKD, and that enrollment has been completed in its Phase 2/3 AMPLITUDE trial.
In the AMPLIFIED study, inaxaplin was given at a 45 mg once-daily dose on top of optimized standard care. The trial enrolled 41 people across two cohorts: patients with AMKD and modest proteinuria and patients with AMKD, type 2 diabetes and proteinuria.
In the first cohort, treatment with inaxaplin led to a 42.7% reduction in urine albumin-to-creatinine ratio, or UACR, at Week 13 compared with baseline. Urine protein-to-creatinine ratio, or UPCR, fell 44.7%.
Vertex said the results were consistent with findings from an earlier Phase 2a study of inaxaplin in patients with AMKD and focal segmental glomerulosclerosis.
In the second cohort, which included patients with AMKD and type 2 diabetes, UACR declined 17.3% at Week 13 compared with baseline, while UPCR declined 25.4%.
Inaxaplin was generally safe and well tolerated in both groups, according to Vertex. There were no serious adverse events related to the treatment, and all reported adverse events were mild or moderate. Headache was the most common adverse event, occurring in 7.3% of participants.
“These results add to the evidence base for inaxaplin and its potential as a first- and best-in-class treatment targeting the underlying cause of AMKD,” said Carmen Bozic, M.D., Executive Vice President, Global Medicines Development and Medical Affairs, and Chief Medical Officer at Vertex.
“The modest proteinuria cohort, which included patients with and without FSGS, delivered remarkable reductions in proteinuria consistent with the original Phase 2a study in patients with AMKD and FSGS,” Bozic said. “We are also excited with the treatment effect, though smaller in magnitude, in the type 2 diabetes cohort.”
Vertex has also completed enrollment in the Phase 2/3 AMPLITUDE study of inaxaplin in patients with severe proteinuria and no other kidney disease-causing comorbidities.
The company expects to report results from a planned interim analysis in early 2027 after patients in the interim analysis cohort reach 48 weeks of treatment. Vertex said positive findings could potentially support accelerated approval in the United States.
AMPLITUDE is evaluating a 45 mg once-daily oral dose of inaxaplin against placebo, both on top of standard care. The primary efficacy endpoint for the final analysis is the change in estimated glomerular filtration rate over two years.
AMKD is a progressive kidney disease caused by two variants in the APOL1 gene. Vertex said the condition affects about 150,000 people in the United States and Europe and currently has no approved therapies.
