Sickle cell
disease

What is 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 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, 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 was identified in 1949 when it was classified as the “first molecular disease,” 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.   

Our aim to address the underlying cause of SCD is to use the body’s own machinery to switch back to producing fetal hemoglobin (HbF; hemoglobin F) through the BCL11A gene. HbF is a form of hemoglobin naturally present at birth, which then switches to the adult form of hemoglobin. We are working on multiple research approaches to achieve this goal. 

We advanced the first-ever CRISPR/Cas9 gene-edited therapy into clinical trials in 2018, and this treatment is now approved in multiple countries for eligible people living with SCD. This autologous, ex vivo therapy uses CRISPR/Cas9 gene-editing technology. 

We know our work is just beginning. We are working to discover and develop conditioning regimens aimed at improving the hematopoietic stem cell transplant process, which is required for gene therapies. In addition, we have internal research programs exploring in vivo gene editing approaches and small molecule treatment options targeting BCL11A 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 our clinical trials website. For information about non-U.S. sites, visit clinicaltrials.gov.