Exagamglogene autotemcel

1. INDICATIONS AND USAGE CASGEVY is indicated for the treatment of patients aged 2 years and older with: sickle cell disease (SCD) with recurrent vaso-occlusive crises transfusion-dependent β - thalassemia (TDT) CASGEVY is an autologous genome edited hematopoietic stem cell-based gene therapy indicated for the treatment of patients aged 2 years and older with: sickle cell disease (SCD) with recurrent vaso-occlusive crises (VOCs). transfusion-dependent β-thalassemia (TDT).

After CASGEVY 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 VOCs. In patients with transfusion-dependent β-thalassemia, γ-globin production improves the α-globin to non-α-globin imbalance thereby reducing ineffective erythropoiesis and hemolysis and increasing total hemoglobin levels, addressing the underlying cause of disease, and eliminating the dependence on regular red blood cell (RBC) transfusions.

For autologous use only. For intravenous use only. Patients are required to undergo hematopoietic stem cell (HSC) mobilization followed by apheresis to obtain CD34 + cells for CASGEVY manufacturing. Dosing of CASGEVY is based on body weight. The minimum recommended dose is 3 × 10 6 CD34 + cells/kg. Full myeloablative conditioning must be administered between 48 hours and 7 days before infusion of CASGEVY. Prophylaxis for seizures should be considered prior to initiating myeloablative conditioning. Prophylaxis for hepatic veno-occlusive disease (VOD) should be considered prior to initiating myeloablative conditioning. Verify that the patient's identity matches the unique patient identification information on the product labels and Lot Information Sheet prior to thaw and infusion. Do not sample, alter, or irradiate CASGEVY. Do not use an in-line blood filter when infusing CASGEVY.

None. None.

Neutrophil Engraftment Failure: Monitor absolute neutrophil counts (ANC) after CASGEVY infusion. Administer rescue cells in the event of neutrophil engraftment failure. Delayed Platelet Engraftment: Monitor platelet counts until platelet engraftment and recovery are achieved. Patients should be monitored for bleeding. Hypersensitivity Reactions: Monitor for hypersensitivity reactions during and after infusion. Off-Target Genome Editing Risk: The risk of unintended, off-target editing in CD34 + cells due to genetic variants cannot be ruled out.

The most common Grade 3 or 4 non-laboratory adverse reactions (incidence ≥ 25%) were mucositis and febrile neutropenia in patients with SCD and TDT, and decreased appetite in patients with SCD. The most common Grade 3 or 4 laboratory abnormalities (≥ 50%) were neutropenia, thrombocytopenia, leukopenia, anemia, and lymphopenia.

No formal drug interaction studies have been performed. CASGEVY is not expected to interact with the hepatic cytochrome P-450 family of enzymes or drug transporters. Granulocyte Colony-Stimulating Factor: Granulocyte Colony-Stimulating Factor (G-CSF) must not be used for CD34 + HSC mobilization of patients with SCD. Hydroxyurea: Discontinue hydroxyurea at least 8 weeks prior to start of mobilization and conditioning. Crizanlizumab: Discontinue the use of crizanlizumab at least 8 weeks prior to start of mobilization and conditioning. Iron Chelators: Discontinue iron chelators at least 7 days prior to initiation of myeloablative conditioning. Avoid the use of non-myelosuppressive iron chelators for at least 3 months and use of myelosuppressive iron chelators for at least 6 months after CASGEVY infusion.

Store the vial(s) in the vapor phase of liquid nitrogen at ≤ -135 °C (≤ -211 °F) until ready for thaw and administration. Do not re-freeze CASGEVY after thawing.