First Patient Enrolled in Phase 1/2 Trial Testing CTX001 for Severe Sickle Cell Disease

A Phase 1/2 clinical trial evaluating investigational therapy CTX001 for severe sickle cell disease (SCD) has enrolled its first patient in the U.S., and treatment is expected to begin by mid-2019.

The trial (NCT03745287), still recruiting participants in Nashville, Tennessee, is looking to enroll 45 adults, 18 to 35 years old, with severe SCD to evaluate the safety and effectiveness of CTX001.

Developed by CRISPR Therapeutics and Vertex Pharmaceuticals, CTX001 uses the CRISPR/Cas9 gene-editing technology and is a potential treatment for diseases of hemoglobin, including beta-thalassemia and SCD.

It is designed to, through genetic engineering, trigger patients’ hematopoietic (bone marrow) stem cells to produce high levels of fetal hemoglobin in red blood cells, compensating for the defective hemoglobin produced by patients and reducing or eliminating their symptoms. These cells are then given back to the patients. Fetal hemoglobin is a form of oxygen-carrying hemoglobin that is naturally present at birth and then normally replaced by its adult form.

Participants in the trial will first undergo myeloablative chemotherapy, a strategy that kills cells in the bone marrow, with the goal of lowering the number of blood-forming cells. Following this, patients receive a single infusion of CTX001 aimed at rebuilding healthy bone marrow.

One of the study’s primary objectives is to assess the proportion of participants with an increase of 20 percent or more in the production of fetal hemoglobin. This will be measured within the first six months after CTX001 infusion. The increase must be maintained for more than three months at the time of analysis.

Additionally, the trial will assess CTX001’s safety by measuring the number and severity of treatment-related side effects and the incidence of transplant-related mortality, among other parameters.

“Beta thalassemia and sickle cell disease are serious, life-threatening diseases, and we are evaluating ex vivo treatment with CTX001 with the goal of creating a one-time potential curative therapy,” David Altshuler MD, PhD, executive vice president and chief scientific officer at Vertex, said in a press release.

“Our collaboration with CRISPR Therapeutics offers an exciting new potential therapeutic approach that complements our strategy of using scientific innovation to create transformative medicines for serious diseases,” Altshuler added.

CTX001 was recently awarded fast track status for the treatment of sickle cell disease by the U.S. Food and Drug Administration.

Vertex also announced that the first patient with transfusion-dependent beta-thalassemia enrolled in a Phase 1/2 trial (NCT03655678) has received CTX001 given in a single infusion into the vein. The trial is recruiting participants in Canada, Germany, and the United Kingdom.

“We have made tremendous progress with CTX001 and are pleased to announce that we’ve treated the first patient with beta thalassemia in this clinical study,” said Samarth Kulkarni, PhD, CEO of CRISPR Therapeutics.

“Treating the first patient in this study marks an important scientific and medical milestone and the beginning of our efforts to fully realize the promise of CRISPR/Cas9 therapies as a new class of potentially transformative medicines to treat serious diseases,” Kulkarni added.