Source: FDA, National Drug Code (US) Revision Year: 2023
CASGEVY is indicated for the treatment of sickle cell disease (SCD) in patients 12 years and older with recurrent vaso-occlusive crises (VOCs).
For autologous use only. For one-time, single dose intravenous use only.
The minimum recommended dose of CASGEVY is 3 × 106 CD34+ cells/kg.
CASGEVY is provided as a single dose for infusion containing a suspension of CD34+ cells in one or more vials. See the Lot Information Sheet provided with the product shipment for additional information pertaining to the number of vials required to achieve the patient-specific dose. Administer all vials.
Confirm that hematopoietic stem cell (HSC) transplantation is appropriate for the patient before mobilization, apheresis and myeloablative conditioning are initiated.
Screen patients for HIV-1, HIV-2, HBV, HCV, and any other infectious agents in accordance with local guidelines before collection of cells for manufacturing. CASGEVY should not be used in patients with active HIV-1, HIV-2, HBV or HCV.
Prior to apheresis it is recommended that patients be transfused with a goal to maintain hemoglobin S (HbS) levels <30% of total hemoglobin (Hb) while keeping total Hb concentration ≤11 g/dL.
Discontinue disease modifying therapies for sickle cell disease (e.g., hydroxyurea, crizanlizumab, voxelotor) 8 weeks before the planned start of mobilization and conditioning.
Patients are required to undergo CD34 HSC mobilization followed by apheresis to isolate the CD34 cells needed for CASGEVY manufacturing.
Plerixafor was used for mobilization. Granulocyte-Colony Stimulating Factor (G-CSF) should not be administered for mobilization in patients with sickle cell disease.
Refer to the prescribing information for the mobilization agent prior to treatment. See Clinical Studies (14) for description of the mobilization regimen used in the clinical trial.
Maximize CD34 cell collection to obtain as many CD34 cells as possible for product manufacturing during each mobilization and apheresis cycle. Perform two consecutive days of cell collection for product manufacturing per cycle, if clinically tolerated. A total collection target of at least 20 × 106 CD34 cells/kg is recommended for product manufacture. Collected cells should be sent for product manufacturing even if the total collection target is not achieved. In addition, at least 2 × 106 CD34 cells/kg is required to be collected for back-up unmodified rescue cells. A third day of cell collection can be used to obtain back-up rescue cells, if needed. If the minimum dose of CASGEVY (3 × 106 CD34+ cells/kg) is not met after initial product manufacturing, the patient will need to undergo additional cycles of mobilization and apheresis. Each mobilization and apheresis cycle must be separated by a minimum of 14 days.
The back-up collection of ≥2 × 106 CD34+ cells/kg of unmodified rescue cells must be collected from the patient and be cryopreserved prior to myeloablative conditioning and infusion with CASGEVY. The unmodified back-up cells may be needed for rescue treatment under any one of the following conditions: (1) compromise of CASGEVY after initiation of myeloablative conditioning and before CASGEVY infusion; (2) neutrophil engraftment failure; or 3. loss of engraftment after infusion with CASGEVY [see Warnings and Precautions (5.1)].
It is recommended that patients be transfused at least 8 weeks prior to the initiation of myeloablative conditioning, with a goal of maintaining hemoglobin S (HbS) levels of <30% of total Hb while keeping total Hb concentration ≤11 g/dL. At initiation of red blood cell exchange or simple transfusions, discontinue disease modifying therapies for sickle cell disease (e.g., hydroxyurea, crizanlizumab, voxelotor).
Stop iron chelation therapy at least 7 days prior to myeloablative conditioning.
Do not begin myeloablative conditioning until the complete set of vial(s) comprising the total dose of CASGEVY has been received and stored at the treatment center and the availability of the back-up collection of unmodified rescue cells is confirmed. See the Lot Information Sheet provided with the product shipment for confirmation of the total dose of CASGEVY.
Administer full myeloablative conditioning prior to treatment with CASGEVY1. Refer to the prescribing information for the myeloablative conditioning agent prior to treatment. See Clinical Studies (14) for the conditioning regimen used in the clinical trial.
Consider administration of anti-seizure prophylaxis. Use agents other than phenytoin prior to initiating busulfan conditioning. Consider prophylaxis for hepatic veno-occlusive disease (VOD)/hepatic sinusoidal obstruction syndrome prior to initiating busulfan conditioning.
CASGEVY must be administered between 48 hours and 7 days after the last dose of the myeloablative conditioning.
CASGEVY contains human cells. Follow universal precautions (wearing gloves, protective clothing, and eye protection) and local biosafety guidelines applicable for handling and disposal of such products to avoid potential transmission of infectious diseases. All material that has been in contact with CASGEVY (solid and liquid waste) should be handled and disposed of as potentially infectious waste in accordance with local biosafety guidelines.
Coordinate the timing of CASGEVY thaw and infusion. Confirm the infusion time in advance and adjust the start time for thaw so that CASGEVY is available for infusion when the patient and healthcare providers are ready. Thaw and infuse one vial at a time.
Premedication: Administer an antipyretic (e.g., acetaminophen) and an antihistamine (e.g., diphenhydramine hydrochloride) prior to administering CASGEVY.
Before thaw, confirm CASGEVY is printed on the vial label and the patient’s identity matches the unique patient information located on the CASGEVY vial(s). Do not infuse CASGEVY if the information on the patient-specific label on any of the vials does not match the intended patient, and contact Vertex at +1-877-634-8789.
A dose of CASGEVY may be contained in one or more cryopreserved patient-specific vial(s). Ensure that the correct number of vials are present. Use the accompanying Lot Information Sheet to confirm the total number of vials to be administered and confirm that each vial is within the expiration date prior to preparation of CASGEVY for infusion.
Inspect the vial(s) for any breaks or cracks prior to thawing. If a vial is compromised, do not infuse the contents. Call Vertex at +1-877-634-8789.
When the dose consists of multiple vials, thaw and administer one vial at a time. While thawing and administering a vial, remaining vials must remain in cryo-storage at ≤ -135°C (≤ -211°F).
Assemble supplies needed to thaw and withdraw the product from the vial(s). With the exception of the water bath, these supplies are single use. Assemble sufficient supplies for each vial to be administered:
Thawing the CASGEVY vials:
CASGEVY is for autologous use only. Before infusion, confirm that the patient’s identity matches the unique patient identifiers on the CASGEVY vial(s). Do not infuse CASGEVY if the information on the patient-specific label does not match the intended patient.
A patient’s dose may consist of multiple vials. All vials must be administered. Use the Lot Information Sheet to confirm the total number of vials to be administered. The entire volume of each vial provided should be infused. If more than one vial is provided, administer each vial completely before proceeding to thaw and infuse the next vial.
1. Attaching the vial adapter and filter:
a. Remove the flip-away tab of the vial cap; clean the septum with an alcohol swab.
b. Remove the cap on the vial adapter spike.
c. With the thumb and forefinger of both hands, push the adapter into the vial septum, applying equal pressure until there is a single pop.
d. Pull up on the adapter until you feel it lock.
e. Attach the filter to the vial adapter.
2. Withdrawing CASGEVY from the vial:
a. Attach an empty 30 mL syringe to the filter.
b. Withdraw the entire vial product volume.
c. Remove the product-filled syringe from the filter and set aside.
d. Draw 5-10 mL of saline into the empty 10 mL syringe.
e. Attach the saline-filled syringe to the filter.
f. Inject the saline into the CASGEVY vial and remove the empty syringe from the filter. Discard the empty syringe.
g. Attach the product-filled syringe to the filter.
h. Withdraw the contents of the vial into the syringe, then remove the syringe from the filter.
i. Peel the product/patient identifier label from the Lot Information Sheet and affix to the product-filled syringe.
3. Administer CASGEVY through central venous catheter:
a. Perform a two-person confirmation and verification of patient’s identification at the bedside prior to the infusion of each vial(s).
b. Administer CASGEVY as an intravenous bolus (IV push) within 20 minutes of product thaw. Do not use an in-line blood filter or infusion pump when infusing CASGEVY. The total volume of CASGEVY administered within one hour must not exceed 2.6 mL/kg.
c. After administration of each vial of CASGEVY, flush the primary line with 0.9% sodium chloride solution, using enough volume to flush the tubing and the length of the IV catheter.
Repeat steps 1-3 for each remaining vial. If more than one vial is needed to achieve the patient-specific dose, administer each vial completely before proceeding to thaw and infuse the next vial.
Follow standard procedures for patient management after HSC transplantation after CASGEVY infusion.
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