Sickle cell
disease
Vertex is focused on discovering, developing and producing 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.
Vertex is focused on discovering, developing and producing 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.
About sickle cell disease
What is sickle cell disease? Sickle cell disease (SCD) is an inherited blood disorder that affects the red blood cells, which are essential for carrying oxygen to all organs and tissues of the body. SCD causes severe pain, organ damage and shortened life span due to misshapen or “sickled” blood cells. People with SCD experience several complications in addition to pain crises, including strokes, anemia, jaundice and symptoms of heart failure. People with SCD often have spleen damage, which puts them at risk for bacterial infections. Most often, treatment is focused on relieving pain and minimizing organ damage, requiring medication and sometimes monthly blood transfusions and frequent hospital visits. The only cure for SCD today is a stem cell transplant from a matched donor, but this option is only available to a small fraction of people living with SCD. SCD requires a lifetime of treatment and can result in a reduced life expectancy.
How is SCD diagnosed? In the United States and Europe, most newborns are screened for SCD at birth, while symptoms usually take about 6 months to present.
What is the underlying cause of disease? SCD occurs due to a mutation in the beta-globin (HBB) gene. The HBB gene encodes for a key component of hemoglobin, the oxygen-carrying molecule in red blood cells. This mutation causes the production of abnormal hemoglobin, called sickle hemoglobin (HbS). Because of this abnormal hemoglobin, red blood cells become rigid and block small blood vessels, resulting in a lack of oxygen delivered to the tissues. This can cause problems in every organ in the body.
The Vertex approach
We’re investigating genetic therapies aimed at the underlying cause of SCD. The cause of SCD has been known since Linus Pauling described the “first molecular disease” in 1949, yet many people still don't have a treatment to address the underlying cause of their disease. With the discovery of tools like CRISPR gene editing, we now potentially have an opportunity to address diseases at their root cause.
We are collaborating with CRISPR Therapeutics to investigate the use of a gene-editing technology, known as CRISPR/Cas9, to discover and develop a new potential one-time treatment for SCD. Exagamglogene autotemcel (exa-cel), formerly known as CTX001™, is an investigational, autologous, ex vivo CRISPR/Cas9 gene-edited therapy which aims to edit a person’s hematopoietic stem cells to produce fetal hemoglobin (HbF; hemoglobin F). HbF is a form of the oxygen-carrying hemoglobin that is naturally present at birth, which then switches to the adult form of hemoglobin. The aim is to use the body’s own machinery to switch back to producing fetal hemoglobin.
We are working to discover and develop novel targeted conditioning regimens that may enhance the hematopoietic stem cell transplant process, including transplants conducted as part of treatment with ex vivo CRISPR/Cas9 gene-editing therapies. We are also investigating other conditioning regimens to potentially support expansion of stem cell transplant opportunities.
In addition, we have an internal research program exploring oral small molecule treatment options for people living with SCD.
Pipeline
These programs are investigating treatments or outcomes that have not 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.
Our studies
In 2018, Vertex and CRISPR Therapeutics initiated a Phase 1/2/3 study evaluating exa-cel in subjects ages 12-35 with sickle cell disease and recurrent vaso-occlusive crises (VOCs). To learn more, visit the clinical trials website.
In 2019, Vertex and CRISPR Therapeutics initiated a long-term follow-up study evaluating subjects who received exa-cel. To learn more, visit the clinical trials website.
In 2022, Vertex initiated a Phase 3 study evaluating exa-cel in pediatric subjects ages 2-11 with sickle cell disease and recurrent vaso-occlusive crises (VOCs). To learn more, visit the clinical trials website.
In 2022, Vertex initiated a Phase 3b study evaluating exa-cel in subjects ages 12-35 with sickle cell disease characterized by recurrent vaso-occlusive crises (VOCs). To learn more, visit the clinical trials website.