Testing the first potential treatment for AMKD

Daniel Feig, M.D., Ph.D., and other Children’s researchers are leading a trial that provides hope for patients with AMKD.

A team of clinicians and researchers from Children’s of Alabama and the University of Alabama at Birmingham (UAB) has launched a potentially groundbreaking clinical trial testing the first potential treatment for APOL1-mediated kidney disease, or AMKD, a genetic condition linked to mutations in the APOL1 gene that can lead to rapid kidney function decline and, ultimately, kidney failure.

“The gene itself is involved in activation of inflammatory arms of the immune system,” said Daniel Feig, M.D., Ph.D., a pediatric nephrologist at Children’s. The APOL1 gene variant doesn’t just cause AMKD; it also exacerbates other kidney conditions. “Individuals with focal segmental glomerulosclerosis (scarring in the kidneys), IgA nephropathy, or diabetic nephropathy with APOL1 risk variants progress to end-stage kidney disease much faster than those without the risk variants.”

This genetic factor is particularly common in African Americans, contributing significantly to the higher rates of kidney failure seen in this population, Feig said.

The current trial, called AMPLITUDE, is testing the efficacy and safety of a first-in-its-class oral medication called VX-147, or inaxaplin. The drug is designed to inhibit the inflammatory pathway triggered by the APOL1 gene variant. The hope is that blocking this pathway will slow or even stop the progression of AMKD.

“It’s exciting because these patients have no other options for therapy,” Feig said.

An earlier trial evaluating standard-of-care plus inaxaplin in people with two APOL1 variants showed a nearly 50% reduction in proteinuria (a marker of kidney damage) after 13 weeks of treatment and reduction in scar tissue in the kidneys. The most common side effects were headache, back pain and nausea. The study was published in the New England Journal of Medicine.

The current trial is enrolling about 500 adult and pediatric participants, including about 150 children ages 10 to 18. More than 200 centers in the U.S. and other countries are involved.

Those eligible for the trial must have confirmed AMKD (with two APOL1 variants), proteinuria, and reduced kidney function. Participants will be monitored for two years while taking the study medication.

“If we can slow the disease by a number of years, that means these patients don’t need dialysis, they don’t need transplant, they don’t have the risk of kidney failure and their life expectancy is much, much, much longer,” Feig said. “It offers hope to families that have been having a difficult time and are really frustrated by the lack of alternatives.”