Vertex, CRISPR's gene-editing treatment for blood disorders shows promise in early data

DNA
Vertex and CRISPR Therapeutics' treatment, CTX001, is made from a patient’s own stem cells, which are harvested and then edited to increase fetal hemoglobin levels in the patient’s blood cells. (LionFive / Pixabay)

CRISPR Therapeutics and Vertex Pharmaceuticals unveiled early data from the first company-backed study to test a CRISPR-based medicine in humans. The data, from two patients with severe blood disorders, are "promising” for what could be a one-and-done treatment for patients who need chronic care, wrote Cantor Fitzgerald analysts in a note on Tuesday. 

The treatment, CTX001, is in two phase 1/2 studies testing it in people with transfusion-dependent beta thalassemia and those with sickle cell disease. The data come from one patient in each trial. In the two years ahead of starting the studies, the beta thalassemia patient needed an average of 16.5 blood transfusions per year, while the sickle cell patient experienced seven vaso-occlusive crises per year—a common complication of the disease where blood cells stick together and block blood vessels, causing pain and damaging tissues and organs. 

Nine months after receiving CTX001, the beta thalassemia patient no longer needed transfusions and had near-normal hemoglobin levels, the partners reported in a statement. Four months after treatment, the sickle cell patient was free of vaso-occlusive crises and had similar hemoglobin levels. Both patients also had high levels of red blood cells expressing fetal hemoglobin—more than 99% for the former and more than 94% for the latter—a sign that the CRISPR-edited treatment did what it was designed to do. 

RELATED: CRISPR Therapeutics, Vertex start first company-backed human CRISPR trial 

Both beta thalassemia and sickle cell disease are caused by mutations in the beta-globin gene, resulting in missing or defective hemoglobin, the oxygen-carrying component of red blood cells. CTX001 was developed on the knowledge that fetal hemoglobin—found in newborn babies but later replaced by adult hemoglobin—can be protective in adults who have blood disorders. 

The treatment is made from a patient’s own stem cells, which are harvested and then edited to increase fetal hemoglobin levels in the patient’s blood cells. The edited cells are then infused back into the patient where they are expected to produce blood cells with fetal hemoglobin and compensate for defective adult hemoglobin. 

RELATED: Editas, Allergan kick off long-awaited in vivo CRISPR trial 

“Given the severity of both patients at baseline, we view early efficacy data as promising for a potential one-time curative therapy although more follow up is needed,” the analysts wrote.  

“Although we think a larger sample size with longer follow-up is needed before investors can give Vertex substantial credit to this program, we think 2020 will be the year where investors may start to pay more attention,” they wrote. 

Vertex’s stock ticked up 2.3% and CRISPR Therapeutics jumped 17% on Tuesday. 

In both patients, the infused cells grafted into the marrow between 30 and 40 days after treatment. The beta thalassemia patient experienced two serious side effects that were not considered treatment-related: liver disease linked to the conditioning drug use ahead of infusion and pneumonia in the presence of neutropenia, or low levels of neutrophils, a type of white blood cell. The sickle cell patient suffered gall stones, abdominal pain and sepsis in the presence of neutropenia, but the principal investigator deemed these side effects not related to treatment. 

RELATED: Vertex licenses blood disorder gene therapy from CRISPR Therapeutics 

“These data support our belief in the potential of our therapies to have meaningful benefit for patients following a one-time intervention. We continue to enroll these studies as we drive forward to develop CRISPR/Cas9 therapies as a new class of transformative medicines to treat serious diseases,” said Samarth Kulkarni, Ph.D., CEO of CRISPR Therapeutics, in the statement. 

The companies aim to enroll 45 patients in each study and to follow each patient for about two years post-infusion. 

“While the data are exciting, we are still in the early phase of this clinical program. We look forward to continuing to work with physicians, patients, caregivers and families over the coming months and years to bring forward the best possible therapy for these two serious diseases and to continue to accelerate our gene-editing programs for other serious diseases such as Duchenne muscular dystrophy and myotonic dystrophy type 1,” said Vertex CEO Jeffrey Leiden, M.D., Ph.D., in the statement.

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