First CRISPR clinical trial backed by U.S. companies launches

The first clinical trial of CRISPR-Cas9 sponsored by U.S. companies has launched, testing the genome-editing technique in patients with the blood disorder beta thalassemia, according to an announcement posted Friday on the U.S. clinical trials website.

The Phase 1/2 clinical trial, co-sponsored by Vertex Pharmaceuticals and using an experimental treatment from CRISPR Therapeutics, will be conducted at a single hospital in Regensburg, Germany, and aims to recruit up to 12 adults with the inherited disease. Although it was only a matter of time before the start of the first company-sponsored CRISPR clinical trial, Editas Medicine’s experimental treatment for a rare form of blindness was widely expected to be the first in the clinic.

The gene-editing therapy that will be tested, called CTX001, is intended to treat both beta thalassemia and sickle cell disease.
Beta thalassemia is caused by a mutation in the HBB gene that reduces the amount of the oxygen-carrying blood protein hemoglobin a patient is able to produce.

Rather than correcting the disease-causing mutation in gene directly, the therapy targets a region of DNA that acts like a brake on production of a form of hemoglobin that the body usually stops making after the first months of life, called fetal hemoglobin. In the rare cases when a genetic variant keeps production turned on well into childhood and even adulthood, even people with β-thalassemia (or sickle cell) have enough healthy hemoglobin to avoid the worst symptoms of those sometimes-fatal diseases.

The CRISPR therapy being tested is called ex vivo, meaning that blood cells are taken from a patient and altered in the lab (much like CAR-T cancer therapy) and then returned to the patient. In this case, CRISPR molecules are introduced to the blood cells via a virus, and the genome editor alters the fetal hemoglobin “brake.” If all goes well, the CRISPR’d cells will then produce red blood cells that contain fetal hemoglobin.

In May, CRISPR Therapeutics and Vertex announced that the Food and Drug Administration had placed a “clinical hold” on the companies’ application to test CTX001 in sickle cell in a U.S. study, but that the planned Phase 1/2 trial in Europe in adults with β-thalassemia was on track. That is the trial that is now recruiting patients.
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