CTX001 is an investigational therapy that Vertex Pharmaceuticals and CRISPR Therapeutics are developing to treat inherited disorders of hemoglobin such as sickle cell disease and beta-thalassemia.

How does CTX001 work?

Sickle cell disease is caused by a mutation in the HBB gene. This gene provides instructions to make the protein hemoglobin. Hemoglobin is a molecule inside red blood cells that is responsible for carrying oxygen. In sickle cell disease, the mutations result in missing or deficient hemoglobin.

CTX001 uses gene-editing technology to make a genetic change to increase the production of fetal hemoglobin in patients’ red blood cells. Fetal hemoglobin is a form of hemoglobin that exists naturally in newborn babies. The body later replaces it with the adult form of hemoglobin. However, sometimes fetal hemoglobin persists in adults, providing protection for people with sickle cell disease and beta-thalassemia.

For the treatment, researchers first collect a patient’s hematopoietic stem cells. These are cells from the bone marrow that give rise to all the red and white blood cells. They then genetically modify these cells in the laboratory so they are able to produce high levels of fetal hemoglobin. Finally, they reintroduce them into the patient’s body, where they will produce large amounts of red blood cells containing fetal hemoglobin.

CTX001 in clinical trials

Researchers presented the results of preclinical experiments with CTX001 at the American Society of Hematology (ASH) Annual Meeting in December 2017. CTX001 was able to efficiently edit the target gene in more than 90% of hematopoietic stem cells to achieve about 40% of fetal hemoglobin production. Investigators believe this is sufficient to improve a patient’s symptoms. Study results also showed that CTX001 affects only cells at the target site, thereby appearing to be a safe potential treatment.

These positive results prompted CRISPR to partner with Vertex to further develop CTX001. The goal is to market CTX001 as a gene-editing treatment for inherited hemoglobin disorders, including sickle cell disease and beta-thalassemia.

A Phase 1/2 clinical trial (NCT03745287) called CLIMB-SCD-121 was started in November 2018 to investigate the use of CTX001 in sickle cell disease. The open-label, multi-site, single-dose trial is recruiting 45 patients, ages 18 to 35, with severe sickle cell disease in the U.S., Canada, Belgium, Germany, and Italy. Researchers will give participants a single intravenous (into the bloodstream) infusion of CTX001. They will monitor the safety and effectiveness of the treatment for six months to two years.

Researchers reported preliminary results for the first patient in November 2019. Before treatment, the patient averaged seven vaso-occlusive crises (VOCs) a year. At four months after treatment, they were free of VOCs and had hemoglobin levels of 11.3 g/dL. The estimated completion date of the trial is May 2022.

Other information

The U.S. Food and Drug Administration (FDA) granted CTX001 fast track designation in January 2019. This designation allows for faster development and review of drugs that treat a serious medical issue and fill an unmet need.

In May 2020, the FDA also granted the therapy the designation of regenerative medicine advanced therapy (RMAT) for treating severe sickle cell disease and transfusion-dependent beta-thalassemia. The purpose of RMAT is to expedite the development and review of new therapies that treat serious or life-threatening medical conditions, or when they show significant clinical benefits over existing therapies.

 

Last updated: May 13, 2020

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Özge has a MSc. in Molecular Genetics from the University of Leicester and a PhD in Developmental Biology from Queen Mary University of London. She worked as a Post-doctoral Research Associate at the University of Leicester for six years in the field of Behavioural Neurology before moving into science communication. She worked as the Research Communication Officer at a London based charity for almost two years.