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Casgevy Generic Name & Formulations
Legal Class
General Description
Pharmacological Class
How Supplied
Susp (frozen)—1 to 9 vials
Manufacturer
Generic Availability
NO
Mechanism of Action
After infusion, the edited CD34+ cells engraft in the bone marrow and differentiate to erythroid lineage cells with reduced BCL11A expression. Reduced BCL11A expression results in an increase in γ-globin expression and HbF protein production in erythroid cells. In patients with severe sickle cell disease, HbF expression reduces intracellular hemoglobin S (HbS) concentration, preventing the red blood cells from sickling and addressing the underlying cause of disease, thereby eliminating vaso-occlusive crises.
Casgevy Indications
Indications
In patients with sickle cell disease recurrent vaso-occlusive crises or transfusion-dependent β-thalassemia.
Casgevy Dosage and Administration
Adult
For autologous and one-time single-dose IV use only. Confirm that hematopoietic stem cell (HSC) transplantation is appropriate prior to mobilization, apheresis, and myeloablative conditioning. Full myeloablative conditioning must be administered prior to treatment. Prior to myeloablative conditioning: stop iron chelation at least 7 days; prophylaxis for hepatic veno-occlusive disease is recommended; and consider prophylaxis for seizures. Do not use an in-line blood filter or an infusion pump. Must undergo HSC mobilization followed by apheresis to obtain CD34+ cells for product manufacturing; the target number of CD34+ cells to be collected is ≥20×106 CD34+ cells/kg. ≥12yrs: Infuse a minimum dose of 3×106 CD34+ cells/kg between 48hrs and 7 days after the last dose of myeloablative conditioning. If the minimum dose is not met, may undergo additional cycles of mobilization and apheresis, separated by 14 days to obtain more cells. A back-up collection is required for rescue treatment: CD34+ cells of ≥2×106 CD34+ cells/kg. Mobilization, apheresis, myeloablative conditioning, preparation and administration for infusion: see full labeling.
Children
<12yrs: not established.
Casgevy Contraindications
Not Applicable
Casgevy Boxed Warnings
Not Applicable
Casgevy Warnings/Precautions
Warnings/Precautions
Risk for neutrophil engraftment failure. Monitor neutrophil counts and manage infections according to guidelines. Administer rescue CD34+ cells if neutrophil engraftment failure occurs. Risk for delayed platelet engraftment, increased bleeding. Monitor for bleeding accordingly. Obtain platelet counts frequently until platelet engraftment and platelet recovery are achieved. Perform blood cell count determination and other appropriate testing if bleeding symptoms occur. Monitor for hypersensitivity during and post-infusion. Risk for off-target genome editing. Renal or hepatic impairment: not studied; assess for impairment to ensure HSC transplantation is appropriate. Elderly (>65yrs). Patients seropositive for HIV, HBV, HCV. Screen for HIV-1/2, HBV, HCV, and other infectious agents prior to cell collection. Active HIV-1/2, HBV, HCV infection, or prior allogeneic or autologous HSC transplant: not recommended. Advise males and females of reproductive potential to use effective contraception from the start of mobilization through at least 6 months after infusion. Exclude pregnancy status prior to mobilization, conditioning procedures, and before infusion. Pregnancy, nursing mothers: not recommended during conditioning.
Casgevy Pharmacokinetics
See Literature
Casgevy Interactions
Interactions
Concomitant live vaccines: not studied. Granulocyte-colony stimulating factor (G-CSF): not recommended. Discontinue disease-modifying therapies for sickle cell disease (eg, hydroxyurea, crizanlizumab, voxelotor) 8 weeks prior to mobilization and conditioning. Discontinue iron chelators ≥7 days prior to myeloablative conditioning; if chelation required, avoid non-myelosuppressive iron chelators for ≥3 months and myelosuppressive iron chelators for ≥6 months post-infusion.
Casgevy Adverse Reactions
Adverse Reactions
Mucositis, febrile neutropenia, decreased appetite, lab abnormalities (neutropenia, thrombocytopenia, leukopenia, anemia, lymphopenia); hypersensitivity reactions, cholelithiasis, pneumonia, pain, sepsis, others.
Casgevy Clinical Trials
See Literature
Casgevy Note
Not Applicable
Casgevy Patient Counseling
See Literature
