FDA Approves Milestone CRISPR Gene-Editing Therapy for β-Thalassemia Treatment

News

FDA Approves Milestone CRISPR Gene-Editing Therapy for β-Thalassemia Treatment

FDA Approves Milestone CRISPR Gene-Editing Therapy for β-Thalassemia Treatment

FDA has approved the first CRISPR gene-editing therapy for the treatment of a second disease—β-thalassemia.

Recently, the U.S. Food and Drug Administration (FDA) granted approval to Casgevy, a groundbreaking CRISPR-based gene-editing therapy developed by CRISPR Therapeutics, founded by Nobel laureate Emmanuelle Charpentier, in collaboration with Vertex Pharmaceuticals. This therapy is now authorized for the treatment of transfusion-dependent β-thalassemia (TDT) in individuals aged 12 and above.

This approval follows the FDA’s green light in December for Casgevy’s use in treating sickle cell disease (SCD) in individuals aged 12 and above, marking the first FDA approval for a CRISPR-based gene-editing therapy.

FDA Approves Milestone CRISPR Gene-Editing Therapy for β-Thalassemia Treatment

Casgevy, a CRISPR-Cas9 gene-editing autologous cell therapy, aims to help patients effectively overcome blood transfusion dependence and vascular obstruction crises associated with β-thalassemia and sickle cell disease.

Clinical trial results for Casgevy were published in December 2020 in the New England Journal of Medicine under the title “CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia.”

FDA Approves Milestone CRISPR Gene-Editing Therapy for β-Thalassemia Treatment

BCL11A, a transcription factor inhibiting the expression of γ-globin and fetal hemoglobin in red blood cells, is targeted for suppression in theory to reactivate γ-globin expression, thus treating β-thalassemia and sickle cell disease.

The research team obtained CD34+ hematopoietic stem cells and progenitor cells from healthy donors and used the CRISPR-Cas9 gene-editing system with specific targeting of the BCL11A enhancer. Results showed approximately 80% editing at the target site with no signs of off-target edits.

In a study involving one β-thalassemia patient and one sickle cell disease patient, autologous CD34+ cells edited with CRISPR-Cas9 BCL11A enhancer were transfused back. After 18 months of treatment, both patients maintained high levels of edited alleles in their bone marrow and blood, with over 76% editing efficiency in the bone marrow and 60% in the blood. The patients no longer required blood transfusions, and 99% of circulating blood cells expressed fetal hemoglobin (HbF).

As of the latest data, 45 sickle cell disease patients have undergone Casgevy therapy, with 28 experiencing pain relief for at least a year. Additionally, 54 severe β-thalassemia patients received Casgevy treatment, with 39 no longer requiring blood transfusions for at least a year, and the remaining 3 showing a reduction of over 70% in transfusion needs. For 44 β-thalassemia patients, 42 did not need blood transfusions during follow-ups ranging from 1.2 to 37.2 months, and the remaining 2 exhibited a 75% and 89% reduction in transfusion frequency.

While this FDA approval signifies a significant milestone in the progress of CRISPR-based gene therapies, the development of conventional, scalable, safe, and affordable gene-editing therapies poses the next critical challenge.

Notably, the pricing of this therapy is as high as $2.2 million. Addressing how to make this treatment accessible to millions of sickle cell disease patients worldwide, particularly in Africa, is a crucial question.

Professor Jennifer Doudna, a Nobel laureate and pioneer in CRISPR gene editing, has expressed that a one-time, in-body injection gene-editing therapy without the need for ex vivo procedures or bone marrow transplants may become a reality.

The approval of Casgevy is not the end of the journey but a long-awaited beginning.