Exagamglogene autotemcel

Patients with Renal Impairment CASGEVY has not been studied in patients with renal impairment, defined as estimated glomerular filtration rate < 60 mL/min/1.73 m 2 . Patients should be assessed for renal impairment to ensure autologous HSC transplantation is appropriate.

Patients with Hepatic Impairment CASGEVY has not been studied in patients with hepatic impairment. Patients should be assessed for hepatic impairment to ensure autologous HSC transplantation is appropriate.

Preparation Before CASGEVY Infusion Confirm that autologous hematopoietic stem cell (HSC) transplantation is appropriate for the patient before mobilization, apheresis and myeloablative conditioning are initiated. It is recommended that patients with SCD weigh at least 12 kg prior to start of mobilization since patients below this weight may experience difficulty in achieving the minimum target cell dose.

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. Discontinue disease modifying therapies (e.g., hydroxyurea, crizanlizumab) 8 weeks before the planned start of mobilization and conditioning [see Drug Interactions (7.2 , 7.3) ] .

Preparation for Mobilization and Apheresis Sickle Cell Disease : Prior to planned start of mobilization, it is recommended to transfuse red blood cells (RBCs) (simple or exchange) as needed, for a minimum of 8 weeks and continue until initiation of myeloablation or reinitiate transfusion for a minimum of 8 weeks prior to start of myeloablation with a goal to maintain hemoglobin S (HbS) levels < 30% of total hemoglobin (Hb) while keeping total Hb concentration ≤ 11 g/dL.

Transfusion-dependent β thalassemia : Prior to planned start of mobilization, it is recommended to transfuse RBCs as needed, with a goal to maintain hemoglobin (Hb) ≥ 11 g/dL and continue until start of myeloablation or reinitiate transfusion for at least 60 days prior to start of myeloablation. Mobilization and Apheresis HSC mobilization followed by apheresis to isolate the CD34 + cells is required to manufacture CASGEVY.

Refer to the prescribing information for the mobilization agent(s) used, prior to treatment. See Clinical Studies for description of the mobilization agents used in the clinical trials. Alternative mobilization regimens may be considered if clinically indicated. Sickle Cell Disease : Administer plerixafor 0.24 mg/kg/day via subcutaneous injection 2 to 3 hours prior to planned apheresis for a maximum of 3 days.

Do not use Granulocyte Colony-Stimulating Factor (G-CSF) for mobilization in patients with SCD. Transfusion-dependent β thalassemia : Administer G-CSF for 5 to 6 days, starting 4 days prior to plerixafor administration. In non-splenectomized patients, administer 5 μg/kg G-CSF every 12 hours intravenously or subcutaneously.

In splenectomized patients, administer 5 μg/kg G-CSF daily. The dose may be increased to every 12 hours in splenectomized patients if there is no increase in white blood cell (WBC) or peripheral blood CD34 + counts. In all patients, administer plerixafor at 0.24 mg/kg per day for a maximum of 3 days, 4 to 6 hours prior to each planned apheresis.

Perform up to three consecutive days of cell collection for product manufacturing per cycle, if clinically tolerated. A total collection target of at least 20 × 10 6 CD34 + cells/kg is recommended, but as many collected cells as possible should be sent for product manufacture even if the total collection target is not achieved.

Perform additional cycles of mobilization and apheresis if the minimum dose of CASGEVY (3 × 10 6 CD34 + cells/kg) is not met. Separate each mobilization and apheresis cycle by a minimum of 14 days. Collect and cryopreserve an additional ≥ 2 × 10 6 CD34 + cells/kg of unmodified back-up rescue cells prior to myeloablative conditioning and infusion with CASGEVY.

Back-up cells may be needed for engraftment failure or product compromise after myeloablation [see Warnings and Precautions ] . Myeloablative Conditioning Administer full myeloablative conditioning with busulfan or another myeloablative conditioning regimen prior to treatment with CASGEVY. Refer to the prescribing information for the myeloablative conditioning agent prior to treatment.

See Clinical Studies for description of the myeloablative agent used in the clinical trials. Do the following before initiation of myeloablative conditioning: In patients with SCD, transfuse 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.

Discontinue disease modifying therapies for sickle cell disease (e.g., hydroxyurea, crizanlizumab) at initiation of red blood cell exchange or simple transfusions (simple or exchange). In patients with TDT, transfuse to maintain hemoglobin (Hb) ≥ 11 g/dL for 60 days prior to myeloablative conditioning. Stop iron chelation therapy for at least 7 days prior to myeloablative conditioning.

Confirm availability of complete set of vial(s) comprising the total dose of CASGEVY has been received and stored at the treatment center. See the Lot Information Sheet(s) provided with the product shipment for confirmation of the total dose of CASGEVY. Confirm availability of the back-up collection of unmodified rescue cells at the treatment center.

Busulfan Myeloablative Conditioning If busulfan is used for myeloablative conditioning, administer intravenously (IV) for 4 consecutive days via a central venous catheter. Measure busulfan plasma levels by serial blood sampling and adjust dose to maintain exposure in the 4-day cumulative target range. For patients 12 years and older, administer busulfan at a planned starting dose of 3.2 mg/kg/day once-daily (qd) or 0.8 mg/kg every 6 hours (q6h).

For the once-daily dosing, adjust busulfan dose for a four day target cumulative busulfan exposure of 82 mg*h/L (range: 74 to 90 mg*h/L), corresponding to an AUC 0-24h of 5000 μM*min (range: 4500 to 5500 μM*min). For the every 6-hours dosing, adjust for a four day target cumulative busulfan exposure of 74 mg*h/L (range: 59 to 89 mg*h/L), corresponding to an AUC 0-6h of 1125 μM*min (range: 900 to 1350 μM*min).

For patients 2 to less than 12 years of age, every 6-hour dosing is recommended. Administer busulfan for 4 consecutive days, with the first dose according to patient weight (see Table 1 ). [See table below.] In patients 2 to less than 12 years of age, adjust busulfan dose with a 4-day target cumulative busulfan exposure of 82 mg*h/L (range: 74 to 90 mg*h/L), corresponding to a per-dose AUC 0-6h of 1250 μM*min (range: 1125 to 1375 μM*min).

Consider anti-seizure prophylaxis (use agents other than phenytoin) and hepatic veno occlusive disease (VOD)/hepatic sinusoidal obstruction syndrome prophylaxis prior to initiating busulfan conditioning. As CASGEVY is an autologous therapy, immunosuppressive agents are not required after initial myeloablative conditioning.

Administer CASGEVY between 48 hours and 7 days after the last dose of the myeloablative conditioning regimen. Receipt and Storage of CASGEVY CASGEVY is shipped to the treatment center frozen in a vapor phase of one or more liquid nitrogen shipper(s). A Lot Information Sheet is included in each liquid nitrogen shipper. Confirm patient identifiers on the product label(s) and Lot Information Sheet(s).

If there are any concerns about the product or packaging upon receipt, contact Vertex at +1-877-634-8789. Transfer CASGEVY from the vapor phase of nitrogen shipper to the treatment center vapor phase of liquid nitrogen storage at ≤ -135 °C (≤ -211 °F). Preparing for CASGEVY Administration 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 cryostorage 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: Water bath Alcohol swabs Vial adapter (to allow for needleless extraction) 18-micron stainless steel filter 30 mL luer-lock syringe 0.9% sodium chloride (saline, 5 to 10 mL needed for each vial) 10 mL luer-lock syringe for saline rinse Thawing the CASGEVY vials Thaw each CASGEVY vial at 37 °C (98 °F) using a water bath.

Thaw each vial holding the vial neck, gently agitating clockwise and counterclockwise. Thawing of each vial can take between 10 to 15 minutes. Thawing is complete when ice crystals are no longer visible in the vial. Ensure water bath temperature does not exceed 40 °C (104 °F) during thawing. Do not leave CASGEVY unattended during thaw.

Administration 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. [See table below.] 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 autologous HSC transplantation after CASGEVY infusion. Image Image Image Image