Vertex Phase 2b AMPLIFIED study shows inaxaplin reduced UACR by 42.7% at Week 13 in APOL1-mediated kidney disease. Review data, safety profile, and trial updates.
Written By: Saniya Katakdhond, PharmD
Reviewed By: Pharmacally Editorial Team
Vertex Pharmaceuticals reported Phase 2b results showing that inaxaplin reduced urine albumin-to-creatinine ratio (UACR) by 42.7% at Week 13 in people with APOL1-mediated kidney disease (AMKD) and modest proteinuria. In patients with AMKD and type 2 diabetes, UACR declined by 17.3% over the same period.
Proteinuria Reduction Across Two AMKD Populations
AMPLIFIED (NCT06794996) was a Phase 2, single-arm, open-label study evaluating inaxaplin 45 mg once daily on top of optimized standard of care for 13 weeks. The study enrolled 41 people across two cohorts, with UACR percentage change from baseline at Week 13 as the primary endpoint.
Cohort 1: AMKD With Modest Proteinuria
The first cohort included 23 people with AMKD and modest proteinuria, defined as UACR of at least 0.1 g/g and less than 0.42 g/g. One participant was excluded from the efficacy analysis because of treatment noncompliance, leaving 22 participants for analysis.
Inaxaplin was associated with a 42.7% reduction in UACR at Week 13 compared with baseline. The reported 95% confidence interval was -58.3% to -21.1%. UPCR, another measure of urinary protein loss, declined by 44.7%.
The baseline mean UACR was 0.28 g/g. The magnitude of the reduction was consistent with findings from an earlier Phase 2a study in patients with AMKD and focal segmental glomerulosclerosis (FSGS), where UACR and UPCR declined by 43.4% and 47.6%, respectively, at Week 13. Most patients in the modest-proteinuria cohort of AMPLIFIED did not have a diagnosis of FSGS.
Cohort 2: AMKD With Type 2 Diabetes
The second cohort enrolled 18 people with AMKD, type 2 diabetes and proteinuria. One participant was excluded from the efficacy analysis because of treatment noncompliance, leaving 17 participants for analysis.
UACR declined by 17.3% at Week 13 compared with baseline, while UPCR decreased by 25.4%. The baseline mean UACR was 0.67 g/g. The reported 95% confidence interval for the UACR change was -36.3% to 7.2%.
Interpreting the AMPLIFIED Findings
Because AMPLIFIED was a single-arm, open-label study without a concurrent placebo control, the results represent changes from baseline rather than a randomized comparative treatment effect. The reported 95% confidence intervals were generated post hoc, so the findings should be interpreted in the context of the study design rather than as evidence of a statistically established benefit versus placebo.
Inaxaplin Targets the APOL1 Disease Pathway
AMKD predominantly affects people of African ancestry who carry two risk variants in the APOL1 gene. Vertex estimates that approximately 150,000 people in the U.S. and Europe are affected.
The genetic variants can cause kidney-cell injury, cell death and glomerular damage, resulting in proteinuria and progressive loss of kidney function. Advanced disease can lead to kidney failure, dialysis or transplantation. No therapies are currently approved specifically for AMKD.
Inaxaplin is an oral small-molecule therapy being developed to target the underlying APOL1-mediated disease process. Its development program is focused on reducing the kidney injury associated with pathogenic APOL1 variants.
Safety Profile Remained Manageable
Inaxaplin was generally safe and well tolerated across both AMPLIFIED cohorts. No serious adverse events were considered related to treatment, and all adverse events were mild or moderate in severity.
Headache was the most common adverse event, occurring in 7.3% of participants. Five people experienced isolated, asymptomatic transaminase elevations, which resolved.
AMPLITUDE Provides the Next Major Test
Vertex has completed enrollment in the global Phase 2/3 AMPLITUDE trial, which evaluates inaxaplin 45 mg once daily versus placebo on top of standard of care in people with AMKD and severe proteinuria without other kidney disease-causing comorbidities.
The final primary efficacy endpoint is the difference in estimated glomerular filtration rate (eGFR) slope between inaxaplin and placebo after two years of treatment. The study also evaluates proteinuria.
Vertex expects data from a pre-planned interim analysis in early 2027, after the interim-analysis cohort reaches 48 weeks of treatment. If positive, the company said the findings could support potential accelerated approval in the U.S.
The AMPLIFIED results extend clinical evaluation of inaxaplin into patients with modest proteinuria and those with AMKD and type 2 diabetes. However, the single-arm design limits direct assessment of comparative efficacy. The placebo-controlled AMPLITUDE study will provide the more definitive test of whether inaxaplin can alter the course of kidney-function decline in AMKD.
Reference
Vertex Announces Positive Results from Phase 2b AMPLIFIED Study of Inaxaplin in Additional Populations of People with APOL1-Mediated Kidney Disease (AMKD) and Completion of Enrollment in the Phase 2/3 AMPLITUDE Trial, Vertex, 22 September 2026
Inaxaplin in Participants with Proteinuric APOL1 Mediated Kidney Disease with or Without Comorbidities (AMPLIFIED), ClinicalTrials.gov ID NCT06794996
About the Writer
Saniya Sanjay Katakdhond (Linkedin) is a Doctor of Pharmacy professional with hands-on experience in patient case review, clinical documentation, medical record analysis, and patient care.
Her hospital experience has strengthened her understanding of clinical conditions, treatment approaches, and multidisciplinary healthcare practices.
With ICH-GCP certification and a research-oriented approach, she brings clinical insight and attention to detail to healthcare content development.
As a healthcare writer, Saniya focuses on translating clinical knowledge and patient-care experience into clear, accurate, and evidence-informed medical content.