The U.S. Food and Drug Administration (FDA) has approved the marketing of CRISPR Cas9 genome-editing cell Casgevy (Exagamglogene Autotemcel, also known as Exa-Cel) for sickle cell disease (SCD) in patients aged 12 years and older with a sexual vasoocclusive crisis (VOC). According to the press release, this is the first FDA-approved CRISPR gene edit**.
Sickle cell disease is an inherited blood disorder whose main problem is mutations in hemoglobin, a protein found in red blood cells that is used to transport oxygen to body tissues. This mutation causes red blood cells to form a crescent or "sickle-shaped". These sickle red blood cells restrict the flow in the blood vessels, restricting the delivery of oxygen to the body's tissues, causing severe pain and organ damage called VOCs. This mutation can cause ongoing complications such as severe pain, life-threatening infections, and anemia.
Currently, the ** method of SCD is to perform a stem cell transplant from a matched donor, but due to the lack of available donors, this option is only available to a small percentage of patients with SCD. Now, a gene is expected to provide a more targeted and effective approach, especially for individuals with rare diseases who currently have limited options.
Casgevy is a genome-editing cell** composed of autologous CD34+ hematopoietic stem cells (HSCs) that are edited by CRISPR Cas9 technology in the erythrocyte-specific enhancer region of the BCL11A gene. Casgevy is designed for one-time administration through a hematopoietic stem cell transplant procedure, in which the patient's own CD34+ cells are modified to reduce the expression of BCL11A in erythroid cells, resulting in increased fetal hemoglobin (HBF) production. HBF is a form of oxygen-carrying hemoglobin that occurs naturally during fetal development and then transitions to the ** form of hemoglobin after birth. CASGEVY has been shown to reduce or eliminate VOCs in patients with SCD.
The approval was based on results from the Phase 3 CLIMB-121 study (NCT03745287), which enrolled 44 patients with SCD who received a single infusion of Casgevy; As of data cut-off, 31 patients were available for evaluation.
The results showed that during the 24-month follow-up period, 93Five percent of patients (29, 31) met the primary endpoint of being free of serious VOCs for at least 12 consecutive months.
None of the patients who received ** experienced transplant failure or rejection. The most common adverse reactions were thrombocytopenia, leukopenia, mouth ulcers, nausea, musculoskeletal pain, abdominal pain, vomiting, fever*** granulocytopenia, headache, and itching.
In the middle of last month, the UK Food and Drug Administration (MHRA) granted conditional marketing approval to Casgevy for sickle cell disease (SCD) with recurrent VOCs and suitable genotypes, or transfusion-dependent thalassemia (TDT) aged 12 years and older. This permission is limited to patients who are unable to receive a stem cell transplant from a matched donor.
In addition, CASGEVY is being reviewed by the European Medicines Agency (EMA) and the Saudi Food and Drug Authority. In the United States, the use of casgevy**TDT is still in the research phase. Vertex has filed a BLA with the FDA regarding the possible use of CASGEVY by patients with TDT 12 years of age and older and has been designated as a target action date of March 30, 2024 for the Prescription Drug User Fee Act (PDUFA).
Reference: 1]'Vertex and CRISPR Therapeutics Announce US FDA Approval of Casgevy (Exagamglogene Autotemcel) for the Treatment of Sickle Cell Disease', press release. vertex pharmaceuticals incorporated；Released on December 8, 2023.
Note: The purpose of this article is to introduce medical and health research, and does not make any basis for medication.