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 can experience painful blood vessel blockages, also known as vaso-occlusive crises (VOCs), that can lead to acute chest syndrome, stroke, jaundice and symptoms of heart failure. Individuals may also experience anemia, which can result in end-organ damage and premature death. VOCs are the hallmark of SCD, often resulting in severe and debilitating pain. Current standard treatment options for SCD are largely symptomatic treatments and do not adequately address the burden of disease or alleviate the need for chronic care. Most often, treatment is focused on relieving pain, minimizing organ damage, maintaining hydration and addressing fevers, requiring medication and sometimes monthly blood transfusions and frequent hospital visits. SCD requires lifelong treatment and significant use of health care resources, and ultimately results in decreased quality of life, reduced life expectancy and reduced lifetime earnings and productivity.

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 cause of SCD has been known since Linus Pauling described the “first molecular disease” in 1949, yet treatment options have been limited for decades. Over the last several years, our teams at Vertex have become pioneers in the cell and genetic therapy space, discovering and developing treatments that target the underlying cause of SCD.  

We advanced the first-ever CRISPR/Cas9 gene-edited therapy into clinical trials in 2018, and this treatment is now approved in some countries for certain eligible people living with SCD. This autologous, ex vivo CRISPR/Cas9 gene-edited therapy aims to edit a person’s hematopoietic stem cells to produce fetal hemoglobin (HbF; hemoglobin F). HbF is a form of hemoglobin that is naturally present at birth, which then switches to the adult form of hemoglobin. Hemoglobin is the protein that carries oxygen throughout the body. The aim is to use the body’s own machinery to switch back to producing fetal hemoglobin. 

We know our work is not done. 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 gene therapies. We are also investigating other conditioning regimens to support expansion of stem cell transplant opportunities. In addition, we have an internal research program exploring small molecule treatment options for people living with SCD.

These programs 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.

For more information about our sickle cell disease studies in the U.S., visit the clinical trials website. For information about non-U.S. sites, visit clinicaltrials.gov.

For more information from Vertex on sickle cell disease, please visit the Newsroom.