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Trade names | Casgevy |
Other names | CTX001, exa-cel |
AHFS/Drugs.com | Casgevy |
License data | |
Routes of administration | Intravenous |
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Exagamglogene autotemcel, sold under the brand name Casgevy, is a gene therapy used for the treatment of sickle cell disease [1] [3] and transfusion-dependent beta thalassemia. [1] It was developed by Vertex Pharmaceuticals and CRISPR Therapeutics. [5]
The most common side effects include low levels of platelets and white blood cells, mouth sores, nausea, musculoskeletal pain, abdominal pain, vomiting, febrile neutropenia (fever and low white blood cell count), headache, and itching. [6]
The treatment was approved in the United Kingdom for the treatment of sickle cell disease and transfusion-dependent beta thalassemia in November 2023. [7] [8] [9] It was approved in the United States for the treatment of sickle cell disease in December 2023 and for the treatment of transfusion-dependent beta thalassemia in January 2024. [6] [10] [11]
Exagamglogene autotemcel is the first cell-based gene therapy treatment utilizing CRISPR/Cas9 gene editing technology to be approved by the US Food and Drug Administration (FDA). [6]
In the UK, exagamglogene autotemcel is indicated for the treatment of transfusion-dependent beta thalassemia and sickle cell disease in patients aged 12 years and older who should be treated with hematopoietic stem cell transplantation but for whom a suitable stem cell donor is not available. [1]
In the US, exagamglogene autotemcel is indicated for the treatment of sickle cell disease in people aged 12 years and older with recurrent vaso-occlusive crises, [4] and for the treatment of people with transfusion-dependent beta-thalassemia. [4] [12]
The gene therapy is made from the recipient's own blood stem cells, which are modified, and are given back as a one-time, single-dose infusion as part of a hematopoietic (blood) stem cell transplant. [6] Prior to treatment, the recipient's own stem cells are collected, and then the recipient must undergo myeloablative conditioning (high-dose chemotherapy), a process that removes cells from the bone marrow so they can be replaced with the modified cells in exagamglogene autotemcel. [6] The modified blood stem cells are transplanted back into the recipient where they engraft (attach and multiply) within the bone marrow and increase the production of fetal hemoglobin (HbF), a type of hemoglobin that facilitates oxygen delivery. [6]
The most common side effects observed in clinical studies included low levels of platelets and white blood cells, mouth sores, nausea, musculoskeletal pain, abdominal pain, vomiting, febrile neutropenia (fever and low white blood cell count), headache and itching. [6]
The safety and effectiveness of exagamglogene autotemcel were evaluated in an ongoing single-arm, multi-center trial in adult and adolescent participants with sickle cell disease. [6] Participants had a history of at least two protocol-defined severe vaso-occlusive crises during each of the two years prior to screening. [6] The primary efficacy outcome was freedom from severe vaso-occlusive crisis episodes for at least twelve consecutive months during the 24-month follow-up period. [6] A total of 44 participants were treated with exagamglogene autotemcel. [6] Of the 31 participants with sufficient follow-up time to be evaluable, 29 (93.5%) achieved this outcome. [6] All treated participants achieved successful engraftment with no participants experiencing graft failure or graft rejection. [6]
The US Food and Drug Administration (FDA) granted the application for exagamglogene autotemcel priority review, orphan drug, fast track, and regenerative medicine advanced therapy designations. [6] The FDA granted approval of Casgevy to Vertex Pharmaceuticals. [6]
In December 2023, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a conditional marketing authorization for the medicinal product Casgevy, intended for the treatment of transfusion‑dependent β‑thalassemia and sickle cell disease. [13] [14] As Casgevy is an advanced therapy medicinal product, the CHMP positive opinion is based on an assessment by the Committee for Advanced Therapies. [13] The applicant for this medicinal product is Vertex Pharmaceuticals (Ireland) Limited. [13]
The therapy has a US list price of US$2.2 million. [15] The cost effectiveness threshold of the therapy in the US is estimated to be between $1.35 million and $2.05 million [16] depending on perspective (healthcare vs limited societal) and assuming the willingness to pay for 1 quality-adjusted life year (QALY) at $100,000–$150,000. [17]
Gene therapy is a medical technology that aims to produce a therapeutic effect through the manipulation of gene expression or through altering the biological properties of living cells.
Thalassemias are inherited blood disorders that result in abnormal hemoglobin. Symptoms depend on the type of thalassemia and can vary from none to severe. Often there is mild to severe anemia as thalassemia can affect the production of red blood cells and also affect how long the red blood cells live. Symptoms of anemia include feeling tired and having pale skin. Other symptoms of thalassemia include bone problems, an enlarged spleen, yellowish skin, pulmonary hypertension, and dark urine. Slow growth may occur in children. Symptoms and presentations of thalassemia can change over time.
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Vertex Pharmaceuticals is an American biopharmaceutical company based in Boston, Massachusetts. It was one of the first biotech firms to use an explicit strategy of rational drug design rather than combinatorial chemistry. It maintains headquarters in South Boston, Massachusetts, and three research facilities, in San Diego, California, and Milton Park, Oxfordshire, England.
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Beta thalassemias are a group of inherited blood disorders. They are forms of thalassemia caused by reduced or absent synthesis of the beta chains of hemoglobin that result in variable outcomes ranging from severe anemia to clinically asymptomatic individuals. Global annual incidence is estimated at one in 100,000. Beta thalassemias occur due to malfunctions in the hemoglobin subunit beta or HBB. The severity of the disease depends on the nature of the mutation.
Deferiprone, sold under the brand name Ferriprox among others, is a medication that chelates iron and is used to treat iron overload in thalassaemia major. It was first approved and indicated for use in treating thalassaemia major in 1994 and had been licensed for use in the European Union for many years while awaiting approval in Canada and in the United States. On October 14, 2011, it was approved for use in the US under the FDA's accelerated approval program.
Sickle cell disease (SCD), one of the hemoglobinopathies, is a group of blood disorders typically inherited. The most common type is known as sickle cell anaemia. It results in an abnormality in the oxygen-carrying protein haemoglobin found in red blood cells. This leads to a rigid, sickle-like shape under certain circumstances. Problems in sickle cell disease typically begin around 5 to 6 months of age. A number of health problems may develop, such as attacks of pain, anemia, swelling in the hands and feet, bacterial infections, and stroke. Long-term pain may develop as people get older. The average life expectancy in the developed world is 40 to 60 years.
Betibeglogene autotemcel, sold under the brand name Zynteglo, is a gene therapy for the treatment for beta thalassemia. It was developed by Bluebird Bio and was given breakthrough therapy designation by the US Food and Drug Administration in February 2015.
Sickle cell-beta thalassemia is an inherited blood disorder. The disease may range in severity from being relatively benign and like sickle cell trait to being similar to sickle cell disease.
Editas Medicine, Inc.,, is a clinical-stage biotechnology company which is developing therapies for rare diseases based on CRISPR gene editing technology. Editas headquarters is located in Cambridge, Massachusetts and has facilities in Boulder, Colorado.
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CRISPR gene editing is a genetic engineering technique in molecular biology by which the genomes of living organisms may be modified. It is based on a simplified version of the bacterial CRISPR-Cas9 antiviral defense system. By delivering the Cas9 nuclease complexed with a synthetic guide RNA (gRNA) into a cell, the cell's genome can be cut at a desired location, allowing existing genes to be removed and/or new ones added in vivo.
bluebird bio, Inc., based in Somerville, Massachusetts, is a biotechnology company that develops gene therapies for severe genetic disorders.
Transfusion-dependent anemia is a form of anemia characterized by the need for continuous blood transfusion. It is a condition that results from various diseases, and is associated with decreased survival rates. Regular transfusion is required to reduce the symptoms of anemia by increasing functional red blood cells and hemoglobin count. Symptoms may vary based on the severity of the condition and the most common symptom is fatigue. Various diseases can lead to transfusion-dependent anemia, most notably myelodysplastic syndromes (MDS) and thalassemia. Due to the number of diseases that can cause transfusion-dependent anemia, diagnosing it is more complicated. Transfusion dependence occurs when an average of more than 2 units of blood transfused every 28 days is required over a period of at least 3 months. Myelodysplastic syndromes is often only diagnosed when patients become anemic, and transfusion-dependent thalassemia is diagnosed based on gene mutations. Screening for heterozygosity in the thalassemia gene is an option for early detection.
CRISPR Therapeutics AG is a Swiss–American biotechnology company headquartered in Zug, Switzerland. It was one of the first companies formed to utilize the CRISPR gene editing platform to develop medicines for the treatment of various rare and common diseases. The company has approximately 500 employees and has offices in Zug, Switzerland, Boston, Massachusetts, San Francisco, California and London, United Kingdom. Its manufacturing facility in Framingham, Massachusetts won the Facilities of the Year Award (FOYA) award in 2022. The company’s lead program, exagamglogene autotemcel, or exa-cel, was granted regulatory approval in December 2023.
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