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

How CTX001 works

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

CTX001 uses gene editing technology to make a genetic change to increase the production of fetal hemoglobin in a patient’s red blood cells. Fetal hemoglobin is a form of hemoglobin that naturally exists in newborn babies and is later replaced by the adult form of hemoglobin. However, sometimes fetal hemoglobin persists in adults, providing protection for people with sickle cell anemia and β-thalassemia.

For the treatment, a patient’s hematopoietic stem cells, which are cells from the bone marrow that give rise to all the red and white cells that form the blood, are collected and then genetically modified in the laboratory so they are able to produce high levels of fetal hemoglobin. These manipulated cells are then reintroduced into the patient’s body, where they will produce large amounts of red blood cells containing fetal hemoglobin, overcoming the hemoglobin deficiencies caused by the disease.

CTX001 in clinical trials

The results of preclinical experiments with CTX001 were presented in December 2017 at the American Society of Hematology (ASH) Annual Meeting. CTX001 was able to efficiently edit the target gene in more than 90 percent of hematopoietic stem cells to achieve about 40 percent of fetal hemoglobin production, which investigators believe is sufficient to improve a patient’s symptoms.

Study results also showed that CTX001 affects only cells at the target site and that it has no off-target effects on hematopoietic stem cells, thereby appearing to be a safe potential treatment.

These positive results prompted CRISPR Therapeutics to start a collaboration with Vertex Pharmaceuticals to develop and commercialize CTX001 as a gene-editing treatment for inherited hemoglobin disorders, including sickle cell anemia and β-thalassemia. CRISPR and Vertex are planning to submit an investigational new drug (IND) application to the U.S. Food and Drug Administration to start a Phase 1/2 clinical trial in sickle cell anemia in the U.S. in 2018.

CRISPR Therapeutics also submitted a clinical trial application (CTA) for CTX001 to advance into a Phase 1/2 clinical trial in patients with β-thalassemia in Europe in 2018. This trial will evaluate the safety and effectiveness of CTX001 in adult patients with transfusion-dependent β-thalassemia.

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