In April 2024, biotechnology company Vertex Pharmaceuticals (“Vertex”) shared via news release that it was advancing its therapeutic candidate inaxaplin (VX-147) into the Phase 3 portion of a Phase 2/3 clinical study. Inaplaxin is an investigational small molecule APOL1 inhibitor. Within the study, researchers are evaluating orally administered inaxaplin at a dose of 45mg once each day for people living with APOL1-mediated kidney disease.

Researchers want to understand the impact of inaxaplin on reducing proteinuria (excess protein in the urine) and improving estimated glomerular filtration rate (eGFR). eGFR is a measure used to assess how well the kidneys are functioning by estimating the rate at which blood is filtered by the glomeruli, the tiny structures in the kidneys responsible for filtering waste and excess fluids from the blood. The study is still recruiting additional participants, including people ages 10-17 living with APOL1-mediated kidney disease.

Reducing proteinuria is important because proteinuria indicates kidney damage. The kidneys normally filter waste from the blood and maintain electrolyte and fluid balance in your body. When the kidneys aren’t working the right way, protein isn’t filtered properly, leaking into the urine and damaging glomeruli. If proteinuria isn’t managed, it can cause continued kidney damage.

The Phase 2a proof-of-concept study found that this therapy reduced urine protein to creatinine ratio by 47.6% over a 13-week period.

What to Know: The Facts on APOL1-Mediated Kidney Disease

APOL1-mediated kidney disease is a type of kidney disease resulting from two variants of the APOL1 (Apolipoprotein L1) gene. The National Kidney Foundation explains that:

Certain APOL1 variants have been linked with different types of kidney disease, including a higher risk of high blood pressure-related chronic kidney disease or kidney failure, focal segmental glomerulosclerosis (FSGS), and HIV-associated nephropathy (HIVAN).

APOL1-mediated kidney disease is more common in people of African or Latin descent. Many people living with APOL1-mediated kidney disease do not know that they have kidney disease until it gets into advanced stages. At this point, affected individuals may experience symptoms such as:

• Proteinuria
• Swelling in the lower extremities
• Fatigue
• Nausea
• Appetite loss
• High blood pressure
• Foamy urine
• Urinating more or less than usual

Of course, symptoms might differ based on which specific kidney disease developed.