Research and Pipeline
Vertex is focused on discovering, developing and commercializing innovative medicines so people with serious diseases can lead better lives. Our scientists don’t see the impossible as an obstacle; they see it as a good place to start.
These studies are investigating treatments or outcomes that have not all received approval from a health authority. The information presented is not intended to convey conclusions of safety or efficacy. There is no guarantee that the outcome of these studies will result in approval by a health authority.
The APOL1 gene is part of the APOL gene family, which plays a role in innate immunity, our body’s built-in system to fight threats. We all have the APOL1 gene, and it’s present in many tissues, including the kidneys. Over the past 3,000 to 10,000 years, the gene evolved in specific ways in people who lived in Western and Central Africa, to protect them from resistant forms of the parasite that causes African sleeping sickness. As people from these regions have migrated around the world, they have taken these certain genetic variants in the APOL1 gene with them. Today, people of African descent may carry these APOL1 variants, including people who identify as African American, Afro-Caribbean and Latinx. In people with two APOL1 genetic variants, an inflammatory exposure (like an infection) can increase the toxic activity of the APOL1 protein in the kidney, and this can lead to kidney disease (like focal segmental glomerulosclerosis) and even kidney failure.
What is APOL1-mediated focal segmental glomerulosclerosis? APOL1-mediated FSGS is a severe kidney disorder, caused by certain APOL1 genetic variants, that leads to protein loss in the blood and progressive loss of kidney function due to scarring. This can cause a number of symptoms, including high levels of protein in the urine (proteinuria), fatigue, swelling in the legs and feet and weight gain.
There are currently no approved treatments that address the underlying cause of APOL1-mediated FSGS. High-dose steroids for a short period of time are often used to help control blood pressure and fluid levels within the body, but their use is limited due to severe side effects. Even with treatment, people with APOL1-mediated FSGS often progress to kidney failure. Kidney failure is treated with frequent, long-term dialysis or a kidney transplant. Both require lifelong treatment and follow-up and carry a high mortality risk.
How is APOL1-mediated FSGS diagnosed? Tests to diagnose APOL1-mediated FSGS usually include blood and urine tests (to check for proteinuria), a kidney biopsy and a genetic test to identify APOL1 gene variants. Other tests may be needed to exclude other causes of FSGS or other types of kidney disease.
What is the underlying cause of disease? In people living with APOL1-mediated FSGS, having two specific variants in the APOL1 gene can lead to kidney cell damages and scarring in the glomeruli, which filter blood in the kidneys. This leads to abnormal protein loss and impairs the kidney’s ability to work properly.
We’re focused on discovering and researching potential medicines aimed at treating the underlying cause of APOL1-mediated kidney diseases. The link between APOL1 gene variants and severe kidney diseases was only identified in 2010. That insight led our team to work to invent new investigational medicines to target the underlying cause of APOL1-mediated kidney diseases, including FSGS.
We are investigating VX-147 and other small molecules aimed at inhibiting variants of APOL1. We continue to discover, research and develop a portfolio of small molecule inhibitors for the potential treatment of APOL1-mediated kidney diseases.
We are investigating VX-147 aimed at inhibiting variants of APOL1.
In addition to investigating candidate medicine VX-147, we continue to research and develop a portfolio of small molecule inhibitors for the potential treatment of APOL1-mediated kidney diseases.
In 2020, Vertex initiated a Phase 2 study evaluating the safety, efficacy and pharmacokinetics of VX-147 in subjects with APOL1-mediated focal segmental glomerulosclerosis (FSGS). To learn more visit clinicaltrials.gov.