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Identification
- Summary
Exagamglogene autotemcel is an autologous CRISPR-Cas9 modified hematopoietic stem cell therapy for the treatment of patients with sickle cell disease and recurrent vaso-occlusive crises.
- Brand Names
- Casgevy
- Generic Name
- Exagamglogene autotemcel
- DrugBank Accession Number
- DB15572
- Background
Sickle cell disease (SCD) is a genetic disorder characterized by the production of abnormal sickle-shaped red blood cells (called hemoglobin S, HbS) that initiate a pathophysiology resulting in severe pain, progressive multi-organ damage, and premature death.1 Treatment options for SCD are largely focused on preventing the production and circulation of HbS and inducing the production of normal fetal hemoglobin (HbF),2,3 including hydroxyurea - a mainstay of treatment since the 1990s - as well as newer agents like crizanlizumab and voxelotor.
Exagamglogene autotemcel is an autologous CRISPR-Cas9 modified CD34+ human hematopoietic stem and progenitor cells which has been investigated in clinical trials for the treatment of severe SCD and severe beta-thalassemia.4 Following engraftment, it causes an increase in the production of HbF and a subsequent decrease in HbS. It was approved by the FDA in December 2023 for the treatment of patients with SCD with recurrent vaso-occlusive crises.5 It is the first CRISPR-based gene editing therapy to be approved in the United States.6 In January 2024, exagamglogene autotemcel received an additional FDA approval for the treatment of transfusion-dependent β-thalassemia.7
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Gene Therapies
Other gene therapies - Synonyms
- Autologous CD34+ cells isolated from mobilised peripheral blood by positive selection, modified by CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) mediated gene editing consisting of a guide RNA (gRNA)
- Exa-cel
- External IDs
- CTX 001
- CTX-001
- CTX001
Pharmacology
- Indication
Exagamglogene autotemcel (Casgevy) is a gene therapy indicated for the treatment of sickle cell disease in patients ≥12 years of age with recurrent vaso-occlusive crises (VOCs).5 It is also indicated for the treatment of patients ≥12 years of age with transfusion-dependent β-thalassemia.5
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Sickle cell disease (scd) •••••••••••• ••••••••• •••••••••••••• •••••• •••••••••• •••••••••• Treatment of Transfusion dependent beta-thalassaemia •••••••••••• •••••••••• •••••••••• - Contraindications & Blackbox Warnings
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Exagamglogene autotemcel exerts its therapeutic effects by increasing the production of normal fetal hemoglobin and decreasing the production of sickle hemoglobin.5 As an autologous therapy, patients must undergo stem cell mobilization and myeloablative conditioning prior to infusion with exagamglogene autotemcel. Plerixafor is preferable for stem cell mobilization, as filgrastim should not be used for mobilization in patients with sickle cell disease.5 Disease-modifying therapies for sickle cell disease - such as hydroxyurea, crizanlizumab, and voxelotor - should be discontinued at the initiation of blood transfusions prior to myeloablative conditioning, and any iron chelating therapies should be discontinued at least 7 days prior.5
- Mechanism of action
Exagamglogene autotemcel is an autologous gene therapy in which patient CD34+ hematopoietic stem cells are edited using CRISPR/Cas9 technology. A precise DNA double-strand break is made at a critical transcription factor binding site (GATA1) in the erythroid-specific enhancer region of the BCL11A gene, which disrupts GATA1 binding and reduces BCL11A protein expression. Following infusion and engraftment, the reduction in BCL11A expression results in an increase in γ-globin expression and downstream fetal hemoglobin production. Fetal hemoglobin expression reduces intracellular sickle hemoglobin concentration, preventing red blood cells from sickling and addressing the underlying cause of the disease.5
- Absorption
As an autologous cell therapy, conventional studies on pharmacokinetics are not applicable to exagamglogene autotemcel.
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
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Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareCefiderocol The risk or severity of myelosuppression can be increased when Exagamglogene autotemcel is combined with Cefiderocol. Chromium picolinate The risk or severity of myelosuppression can be increased when Exagamglogene autotemcel is combined with Chromium picolinate. - Food Interactions
- No interactions found.
Products
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Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Casgevy Injection 8500000 cells/ml Intravenous Vertex Pharmaceuticals (Ireland) Limited 2024-07-10 Not applicable EU 
Casgevy Injection, suspension 13000000 1/1mL Intravenous Roslin Cell Therapies Limited 2023-12-08 Not applicable US 
Casgevy Injection, suspension 13000000 1/1mL Intravenous Vertex Pharmaceuticals Incorporated 2023-12-08 Not applicable US
Categories
- ATC Codes
- B06AX05 — Exagamglogene autotemcel
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Humans
Chemical Identifiers
- UNII
- S53L777GM8
- CAS number
- Not Available
References
- General References
- Doerfler PA, Sharma A, Porter JS, Zheng Y, Tisdale JF, Weiss MJ: Genetic therapies for the first molecular disease. J Clin Invest. 2021 Apr 15;131(8):e146394. doi: 10.1172/JCI146394. [Article]
- Meier ER: Treatment Options for Sickle Cell Disease. Pediatr Clin North Am. 2018 Jun;65(3):427-443. doi: 10.1016/j.pcl.2018.01.005. [Article]
- Brandow AM, Liem RI: Advances in the diagnosis and treatment of sickle cell disease. J Hematol Oncol. 2022 Mar 3;15(1):20. doi: 10.1186/s13045-022-01237-z. [Article]
- BioPharma Dive: First look at CRISPR, Vertex gene-editing therapy hints at treatment potential [Link]
- FDA Approved Drug Products: Casgevy (exagamglogene autotemcel) suspension for intravenous infusion (January 2024) [Link]
- FDA Press Announcements: FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease [Link]
- Vertex Pharmaceuticals News Release: Vertex Announces US FDA Approval of CASGEVY™ (exagamglogene autotemcel) for the Treatment of Transfusion-Dependent Beta Thalassemia [Link]
- External Links
- 2671667
- Wikipedia
- Exagamglogene_autotemcel
Clinical Trials
- Clinical Trials
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Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Intravenous 8500000 cells/ml Injection, suspension Intravenous 13000000 1/1mL - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Drug created at November 19, 2019 16:39 / Updated at January 20, 2024 14:03