In Another Win for CRISPR, FDA Approves Casgevy for Beta Thalassemia

In a further achievement for CRISPR technology, the U.S. Food and Drug Administration (FDA) has granted approval for Casgevy (exa-cel), a CRISPR/Cas9 gene-edited cell therapy developed by Vertex and CRISPR Therapeutics. Casgevy is now authorized for the treatment of transfusion-dependent beta thalassemia (TDT) in patients aged 12 and older. This approval is indicative of the maturation of the gene and cell therapy market, which is currently valued at $15 billion and is projected to exceed $80 billion in the next decade.

The recent FDA approval for Casgevy to treat sickle cell disease, along with the approval of Lyfgenia, Bluebird Bio’s gene therapy for sickle cell, underscores the expanding applications of gene therapies. Furthermore, in November, the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) granted conditional marketing authorization for Casgevy in both sickle cell disease and TDT.

With this approval, Casgevy becomes the first CRISPR gene-editing technology-based treatment for transfusion-dependent beta thalassemia (TDT) available in the United States. TDT is an inherited blood disease characterized by low levels of functioning hemoglobin, which is responsible for carrying oxygen.

Reshma Kewalramani, MD, CEO and president of Vertex, expressed excitement about securing approval for TDT shortly after the historic FDA approval of Casgevy for sickle cell disease. Casgevy offers new potentially curative treatment options for patients with TDT.

Given that Casgevy administration requires expertise in stem cell transplantation, Vertex is establishing a network of independently operated authorized treatment centers (ATCs) across the U.S. to provide the treatment. Presently, all nine existing U.S. ATCs can offer Casgevy to eligible patients with either TDT or sickle cell disease. Additional ATCs are set to be activated in the coming weeks, and a complete list of ATCs is accessible at CASGEVY.com.

Transfusion-dependent beta thalassemia (TDT) necessitates regular blood transfusions and iron chelation therapy throughout an individual’s life. Due to anemia, patients may suffer from fatigue and shortness of breath, while infants may experience failure to thrive, jaundice, and feeding problems. Complications of TDT can include an enlarged spleen, liver, and/or heart, misshapen bones, and delayed puberty.

Patients with TDT often face reduced life expectancy, diminished quality of life, and lower lifetime earnings and productivity. In the United States, the median age of death for individuals with TDT is 37 years. While a stem cell transplant from a matched donor can cure the condition, this option is only available to a small fraction of people with TDT due to the scarcity of donors.

The one-time Casgevy treatment from Vertex and CRISPR Therapeutics is priced at $2.2 million. The companies estimate that lifetime healthcare costs for managing TDT in the U.S. exceed $5 million.

Casgevy is a non-viral, ex vivo CRISPR/Cas9 gene-edited cell therapy designed for specific patients with sickle cell disease or transfusion-dependent beta thalassemia (TDT). The therapy involves extracting a patient’s own hematopoietic stem and progenitor cells, which are then edited. The edits are implemented at the erythroid specific enhancer region of the BCL11A gene through a precise double-strand break. This alteration results in the production of elevated levels of fetal hemoglobin (HbF) in red blood cells. HbF is the type of hemoglobin typically present during fetal development, transitioning to the adult form after birth.