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Casgevy (EXAGAMGLOGENE AUTOTEMCEL)
Edited CD34+ cells with reduced BCL11A expression increase γ-globin and HbF production, preventing sickling and transfusion dependence.
CASGEVY is an autologous genome-edited hematopoietic stem cell therapy indicated for patients aged 12+ with sickle cell disease with recurrent vaso-occlusive crises or transfusion-dependent β-thalassemia. The therapy edits CD34+ cells ex vivo to reduce BCL11A expression, increasing γ-globin and HbF production to address underlying disease mechanisms. Multiple drug interactions require discontinuation of hydroxyurea, voxelotor, crizanlizumab, and iron chelators at specified intervals before and after treatment. Conventional pharmacokinetic parameters are not applicable to this cellular therapy modality.
At a glance
| Generic name | EXAGAMGLOGENE AUTOTEMCEL |
|---|---|
| Drug class | Autologous genome-edited hematopoietic stem cell therapy |
| Target | BCL11A |
| Modality | Gene therapy |
| Phase | FDA-approved |
| First approval | 2023 |
Mechanism of action
CASGEVY consists of autologous CD34+ hematopoietic stem cells edited ex vivo to reduce BCL11A expression. The edited cells engraft in bone marrow and differentiate to erythroid lineage cells with increased γ-globin expression and HbF protein production. In sickle cell disease, elevated HbF reduces intracellular hemoglobin S concentration, preventing red blood cell sickling and eliminating vaso-occlusive crises. In transfusion-dependent β-thalassemia, γ-globin production corrects the α-globin to non-α-globin imbalance, reducing ineffective erythropoiesis and hemolysis while increasing total hemoglobin levels, thereby eliminating transfusion dependence.
Approved indications
Common side effects
- Febrile neutropenia
- Mucositis
- Abdominal pain
- Cholelithiasis
- Decreased appetite
- Musculoskeletal pain
- Pruritus
- Neutropenia
- Thrombocytopenia
- Veno-occlusive liver disease
- Serious adverse reactions
Drug interactions
- Granulocyte-Colony Stimulating Factor (G-CSF)
- Hydroxyurea
- Voxelotor and Crizanlizumab
- Iron Chelators (non-myelosuppressive)
- Iron Chelators (myelosuppressive)
Key clinical trials
- A Long-term Follow-up Study in Participants Who Received CTX001 (PHASE3)
- Evaluation of Efficacy and Safety of a Single Dose of Exa-cel in Participants With Severe Sickle Cell Disease, βS/ βC Genotype (PHASE3)
- Evaluation of Efficacy and Safety of a Single Dose of CTX001 in Participants With Transfusion-Dependent β-Thalassemia and Severe Sickle Cell Disease (PHASE3)
- An Optimised GA Interventional Trial (Opti-GAIN) to Test if Treatment With CTx001 is Safe and Works for People With Geographic Atrophy (GA) (PHASE1, PHASE2)
- Evaluation of Safety and Efficacy of CTX001 in Pediatric Participants With Severe Sickle Cell Disease (SCD) (PHASE3)
- Evaluation of Safety and Efficacy of CTX001 in Pediatric Participants With Transfusion-Dependent β-Thalassemia (TDT) (PHASE3)
- A Safety and Efficacy Study Evaluating CTX001 in Participants With Transfusion-Dependent β-Thalassemia (PHASE2, PHASE3)
- A Safety and Efficacy Study Evaluating CTX001 in Subjects With Severe Sickle Cell Disease (PHASE2, PHASE3)
Primary sources
Every claim on this page is sourced from regulatory or scientific primary sources. See our editorial policy for full methodology.
| Source | Used for |
|---|---|
| FDA label | Mechanism, indications, dosing, boxed warnings, drug interactions |
| ClinicalTrials.gov | Trial enrolment, design, endpoints, results |
Competitive intelligence
For the full competitive landscape — auto-detected comparators, recent regulatory actions across the set, upcoming PDUFA, patent timeline, sponsor landscape:
- Casgevy CI brief — competitive landscape report
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