EMA Grants PRIME Designation to Vertex and CRISPR’s Therapy for Transfusion-Dependent Beta Thalassemia

Rare Daily Staff

The European Medicines Agency granted Priority Medicines designation to Vertex Pharmaceuticals and CRISPR Therapeutics’ CTX001, an experimental, autologous, ex vivo CRISPR/Cas9 gene-edited therapy for the treatment of transfusion-dependent beta thalassemia.

Transfusion-dependent beta thalassemia (TDT) is a genetic hemoglobinopathy that affects the ability of the blood to deliver oxygen to the cells throughout the body. TDT reduces the production of hemoglobin, the iron-containing protein in red blood that carries oxygen to cells.

CTX001 is being evaluated for patients suffering from TDT or severe sickle cell disease (SCD), in which a patient’s hematopoietic stem cells are edited to produce high levels of fetal hemoglobin (HbF) in red blood cells. HbF is a form of the oxygen-carrying hemoglobin that is naturally present at birth, which then switches to the adult form of hemoglobin. The elevation of HbF by CTX001 has the potential to alleviate transfusion requirements for patients with TDT and reduce painful and debilitating sickle crises for patients with SCD.

PRIME is a regulatory mechanism that provides early and proactive support to developers of promising medicines to optimize development plans and speed up evaluations so these medicines can reach patients faster. The goal of PRIME is to help patients benefit as early as possible from innovative new therapies that have demonstrated the potential to significantly address an unmet medical need. PRIME designation was granted based on clinical data from CRISPR and Vertex’s ongoing phase 1/2 trial of CTX001 in patients with TDT.

CTX001 was granted PRIME designation for the treatment of sickle cell disease in 2020. It has also received Regenerative Medicine Advanced Therapy, Fast Track, Orphan Drug, and Rare Pediatric Disease designations from the U.S. Food and Drug Administration (FDA) for both TDT and SCD. CTX001 has also been granted Orphan Drug designation from EMA for both TDT and SCD.

CTX001 is being studied in two ongoing clinical trials as a potential one-time therapy for patients suffering from TDT and severe SCD. The ongoing phase 1/2 open-label trial, CLIMB-Thal-111, is designed to assess the safety and efficacy of a single dose of CTX001 in patients ages 12 to 35 with TDT. The trial will enroll up to 45 patients and follow patients for approximately two years after infusion. Each patient will be asked to participate in a long-term follow-up trial.

The ongoing phase 1/2 open-label trial, CLIMB-SCD-121, is designed to assess the safety and efficacy of a single dose of CTX001 in patients ages 12 to 35 with severe SCD. The trial will enroll up to 45 patients and follow patients for approximately two years after infusion. Each patient will be asked to participate in a long-term follow-up trial.

Another trial, CLIMB-131, is a multi-site, long-term observational study to evaluate the safety and efficacy of CTX001 in patients who received CTX001 in CLIMB-111 or CLIMB-121. The study is designed to follow participants for up to 15 years after CTX001 infusion.

Patients who enroll in these trials will have their own hematopoietic stem and progenitor cells collected from peripheral blood. The patient’s cells will be edited using the CRISPR/Cas9 technology. The edited cells, CTX001, will then be infused back into the patient as part of a stem cell transplant, a process which involves, among other things, a patient being treated with myeloablative busulfan conditioning. Patients undergoing stem cell transplants may also encounter side effects (ranging from mild to severe) that are unrelated to the administration of CTX001. Patients will initially be monitored to determine when the edited cells begin to produce mature blood cells, a process known as engraftment. After engraftment, patients will continue to be monitored to track the impact of CTX001 on multiple measures of disease and for safety.