By V. Scantlebury, MD, FACS, DPC Education Center Healthcare Consultant

A recent article in the New England Journal of Medicine by Egbuna and colleagues (1) reported that in a small study, patients with focal segmental glomerulosclerosis (FSGS) who are homozygous for the variants in the gene encoding apolipoprotein L1 (APOL1) when treated with the drug Inaxaplin, (which inhibits APOL1 function) demonstrated significantly reduced protein excretion. Inaxaplin is the first investigational therapy that is directed at treating  APOL1-mediated kidney disease.

Why is this significant? There is a disproportionate burden of chronic kidney disease in persons of African ancestry. FSGS and other forms of kidney disease affect African Americans and persons of African descent to a much larger extent than those of European ancestry.

The presence of the gene APOL1 and both variants G1 and G2 have been associated with kidney disease in people of African descent, with a 10-fold chance of developing FSGS. Inheriting one variant does not pose the same risks. It is estimated that as many as 13% of African Americans who have two of the APOL1 genetic variants will develop kidney disease.

From a cohort of 16 enrollees, this single-group phase 2a clinical study was conducted in 13 participants who had two APOL1 variants and biopsy proven FSGS and proteinuria. The drug Inaxaplin was given daily for 13 weeks. In 13 patients who adhered to the study criteria, there was a significant improvement in proteinuria.

With prior investigations that included in-vivo studies in animals, the use of Inaxaplin to prevent proteinuria in this small study represents an exciting potential treatment for APOL1-associated kidney disease, and an opportunity to target those patients with African heritage who may be at greater risks for kidney failure.

According to Dr Egbuna’s team, “these data provide a rationale to test the hypothesis that with a longer treatment period, Inaxaplin therapy may prevent or slow progression to end-stage kidney disease.”


Clinical Trial
N Engl J Med 2023 Mar 16;388(11):969-979.
Inaxaplin for Proteinuric Kidney Disease in Persons with Two APOL1 Variants
Ogo Egbuna 1, et al.