Vertex Pharmaceuticals has announced positive results from the 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 (T2D).

In this study, inaxaplin was evaluated as a 45 mg once-daily dose on top of optimised Standard of Care (SoC). Forty-one people were enrolled and dosed in 2 cohorts: people with AMKD with modest proteinuria (UACR ≥0.1 g/g to <0.42 g/g) were eligible for cohort 1 (N=23), and people with AMKD, T2D 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 optimised SoC led to a reduction of -42.7 percent (95 percent CI -58.3 percent, -21.1 percent) in UACR at week 13 compared to baseline. UPCR decreased by -44.7 percent 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 percent and a reduction in UPCR of -47.6 percent 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 optimised SoC led to a reduction in UACR at week 13 of -17.3 percent (95 percent CI -36.3 percent, 7.2 percent) compared to baseline. UPCR decreased by -25.4 percent from baseline at week 13.

Inaxaplin was generally safe and well tolerated across both cohorts. There were no Serious Adverse Events (SAEs) related to inaxaplin. All AEs were mild or moderate in severity. The most common AE (occurring in >5 percent of subjects) was headache (7.3 percent). Five people had isolated, asymptomatic transaminase elevations, which resolved.

Carmen Bozic, MD, Executive Vice President, Global Medicines Development and Medical Affairs, and Chief Medical Officer, Vertex, said, “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. 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. We are also excited with the treatment effect, though smaller in magnitude, in the Type 2 Diabetes cohort. We look forward to discussing the AMPLIFIED results with regulators in the context of the AMPLITUDE pivotal study.”

Vertex has completed full enrollment in the phase 2/3 AMPLITUDE study of inaxaplin in people with severe proteinuria and no other kidney disease-causing comorbidities. Vertex is on track to share data from the pre-planned interim analysis of AMPLITUDE in early 2027 once the IA cohort reaches 48 weeks of treatment. If positive, the data could form the basis for potential accelerated approval in the US.

Glenn Chertow, MD, MPH, Professor of Medicine, Stanford University School of Medicine, and Chair of the Vertex APOL1 Program Steering Committee, said, “These results are very convincing. These patients were already well treated with foundational Chronic Kidney Disease therapies and treatment with inaxaplin led to additional reductions in proteinuria. As someone who treats this rapidly progressing disease where unmet need is high, I am looking forward to the AMPLITUDE interim analysis and am hopeful that we’ll soon have a potentially disease-specific and disease-modifying therapy to offer to patients living with AMKD.”