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 human trypanosomiasis. As people from these regions have migrated around the world, they have taken these certain genetic mutations in the APOL1 gene with them. Today, people of African ancestry may carry these APOL1 mutations, including people who identify as African American, Afro-Caribbean and Latino/Latina.
Having two mutations in the APOL1 gene is associated with increased risk of kidney disease, which can have various clinical presentations including, but not limited to, focal segmental glomerulosclerosis (FSGS).
What is APOL1-mediated kidney disease? APOL1-mediated kidney disease is a kidney disorder associated with certain APOL1 genetic mutations. The disease can lead to kidney cell injury, cell death and damage to the glomeruli (which filter blood in the kidney). This leads to abnormal amounts of protein in the urine (or proteinuria) and decreased ability of the kidney to function. This can cause a number of symptoms, including fatigue, swelling in the legs and feet, and weight gain.
There are currently no approved treatments that address the underlying cause of APOL1-mediated kidney disease. 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 kidney disease 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 kidney disease diagnosed? Tests to diagnose APOL1-mediated kidney disease usually include blood and urine tests (to check for proteinuria and to measure kidney function). A kidney biopsy may be required to better understand the nature of the kidney injury, and a genetic test is needed to identify whether a person has two APOL1 genetic mutations.
What is the underlying cause of disease? In people living with two APOL1 genetic mutations, an inflammatory exposure (like an infection) can increase the toxic activity of the APOL1 protein in the kidney, which can lead to kidney cell injury, cell death and damage to the glomeruli (which filter blood in the kidney). This leads to abnormal amounts of protein in the urine (or proteinuria) and decreased ability of the kidney to function.
We’re focused on researching and discovering potential medicines aimed at treating the underlying cause of APOL1-mediated kidney disease. In 2010, scientists discovered that people who inherit two mutations in the APOL1 gene are at significantly increased risk of developing kidney disease. Research has also shown that the course of kidney disease is more rapidly progressive in patients with two APOL1 genetic mutations than in patients without them. That insight led our team to work to invent new investigational medicines to target the underlying cause of APOL1-mediated kidney disease. We are investigating VX-147 and other small molecules aimed at inhibiting the function of the APOL1 protein. We continue to discover, research and develop a portfolio of small molecule inhibitors for the potential treatment of APOL1-mediated kidney disease.
We are currently in Phase 2/3. We are investigating VX-147 aimed at inhibiting high-risk 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 disease.
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 or clinicaltrialsregister.eu.
In 2022, Vertex initiated a Phase 2/3 study evaluating the safety, efficacy and pharmacokinetics of VX-147 in subjects with APOL1-mediated kidney disease. To learn more visit clinicaltrials.gov.