Vertex Reports Positive Inaxaplin Data, Completes AMPLITUDE Enrollment

Vertex Pharmaceuticals said Tuesday that its experimental kidney-disease drug inaxaplin reduced urinary albumin in two additional groups of people with APOL1-mediated kidney disease, while the company also completed enrollment in its pivotal AMPLITUDE trial. At Week 13, the Phase 2b AMPLIFIED study showed a 42.7% reduction from baseline in urine albumin-to-creatinine ratio, or UACR, in participants with modest proteinuria and a 17.3% reduction in participants who also had type 2 diabetes.

Testing in AMPLIFIED extends inaxaplin beyond the primary AMKD population being studied in AMPLITUDE. It also comes with important limits. AMPLIFIED was an open-label study without a placebo arm, and the confidence interval around the 17.3% UACR reduction in the type 2 diabetes cohort ranged from a 36.3% reduction to a 7.2% increase. That interval crossed zero, making the size of the treatment effect in that group less certain than the headline percentage alone suggests.

AMPLIFIED showed a larger effect in the modest-proteinuria cohort

In its Sept. 22 clinical update, Vertex said 41 people were enrolled and dosed across the two AMPLIFIED cohorts. Participants received 45 milligrams of inaxaplin once daily on top of optimized standard care for 13 weeks. UACR, the primary endpoint, measures albumin leakage into urine and is used to track kidney damage and proteinuria.

Among people with AMKD and modest proteinuria, defined in the study as UACR of at least 0.1 grams per gram but less than 0.42 grams per gram, Vertex reported a 42.7% geometric mean reduction in UACR at Week 13. The 95% confidence interval ranged from a 21.1% to 58.3% reduction. Urine protein-to-creatinine ratio, or UPCR, fell 44.7% in that cohort, with a 95% confidence interval of 21.9% to 60.9% reduction.

Those results were close to the company’s earlier Phase 2a experience in people with AMKD and focal segmental glomerulosclerosis, where Vertex previously reported a 43.4% reduction in UACR and a 47.6% reduction in UPCR at Week 13. Vertex said most participants in the new modest-proteinuria cohort did not have an FSGS diagnosis, which is one reason the company views AMPLIFIED as an expansion of the populations in which inaxaplin might eventually be used.

People in the second cohort had AMKD, type 2 diabetes and proteinuria. UACR fell 17.3% at Week 13, while UPCR fell 25.4%. For UPCR, the 95% confidence interval ranged from a 45.1% reduction to a 1.4% increase, again crossing zero. Diabetes can itself contribute to kidney disease and proteinuria, so this cohort was deliberately separated from the primary AMKD population in AMPLITUDE.

Safety was generally favorable, but the study was small and open label

Vertex said inaxaplin was generally safe and well tolerated across both AMPLIFIED cohorts. No serious adverse events were considered related to the drug, and all reported adverse events were mild or moderate in severity. Headache was the most common event occurring in more than 5% of participants, affecting 7.3%. Five participants had isolated, asymptomatic elevations in liver transaminases, which the company said resolved.

Efficacy analyses included fewer people than the 41 initially enrolled and dosed. Under the prespecified statistical plan, two participants, one from each cohort, were excluded because they were noncompliant with treatment. At Week 13, the analyses covered 18 people in the modest-proteinuria cohort and 14 in the type 2 diabetes cohort who were on treatment and had an assessment. Vertex also noted that the reported 95% confidence intervals were generated post hoc.

Those design details matter when interpreting the results. Without a placebo group, AMPLIFIED cannot directly measure how much of the observed change would have occurred without inaxaplin over the same period. Small sample sizes also make estimates more sensitive to individual outcomes. The findings provide an additional signal for the drug across broader AMKD populations rather than the controlled pivotal evidence needed for a registration decision.

Inaxaplin is an oral small-molecule inhibitor of APOL1 channel function. AMKD occurs in people with two risk variants in the APOL1 gene and can cause progressive kidney damage and proteinuria. Vertex has estimated that roughly 250,000 people in the United States and Europe have AMKD when patients with comorbidities are included, and there are currently no therapies specifically approved for the disease.

AMPLITUDE now becomes the key regulatory readout

Alongside the Phase 2b results, Vertex said it has completed full enrollment in AMPLITUDE, its global Phase 2/3 trial of inaxaplin in people with severe proteinuria and no other kidney-disease-causing comorbidities. AMPLITUDE evaluates the same 45-milligram once-daily dose on top of standard care against placebo.

Enrollment in the prespecified interim-analysis cohort was completed in 2025. Once that cohort reaches 48 weeks of treatment, Vertex plans to evaluate kidney-function and proteinuria measures, including estimated glomerular filtration rate slope and change in proteinuria versus placebo. The company expects to report the interim results in early 2027. If those data are supportive, Vertex has said they could form the basis for seeking accelerated approval in the United States.

AMPLITUDE is therefore more consequential for inaxaplin’s regulatory path than the newly reported AMPLIFIED study. The Phase 2b results give Vertex evidence in patients with less proteinuria and in patients whose kidney disease is complicated by type 2 diabetes, but AMPLITUDE is the controlled pivotal program designed to test inaxaplin in primary AMKD. A positive interim analysis would move the program closer to a potential filing, while a weaker result would call into question how well the proteinuria reductions seen in smaller studies translate into a broader, controlled population. Vertex expects that interim analysis in early 2027, after 48 weeks of treatment in the prespecified cohort.