Casgevy (exagamglogene autotemcel) - 2 indications

Scroll down for more information on each indication:

• for the treatment of sickle cell disease (SCD) in patients 12 years and older with recurrent vaso-occlusive crises; Approved .
• for the treatment of transfusion-dependent beta thalassemia (TDT) in patients 12 years and older.

General Information

Casgevy (exagamglogene autotemcel) is an autologous genome edited hematopoietic stem cell-based gene therapy. 

Casgevy is specifically indicated:

• for the treatment of sickle cell disease (SCD) in patients 12 years and older with recurrent vaso-occlusive crises.
• for the treatment of transfusion-dependent beta thalassemia (TDT) in patients 12 years and older.

Dosing/Administration

• Casgevy is suppled as a suspension for intravenous use. For autologous 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 × 106 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.
• 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.
• Administer each vial of Casgevy via intravenous infusion within 20 minutes of thaw.

Mechanism of Action

Casgevy (exagamglogene autotemcel) is an autologous genome edited hematopoietic stem cell-based gene therapy. 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.

Side Effects

Adverse effects associated with the use of Casgevy may include, but are not limited to, the following:

• mucositis
• febrile neutropenia
• decreased appetite
• Grade 3 or 4 laboratory abnormalities (≥ 50%): neutropenia, thrombocytopenia, leukopenia, anemia, and lymphopenia

Indication 1 - sickle cell disease

approved December of 2023

The FDA approval of Casgevy was based on an ongoing single-arm, multi-center trial in adult and adolescent patients with SCD. Patients had a history of at least two protocol-defined severe VOCs during each of the two years prior to screening. The primary efficacy outcome was freedom from severe VOC episodes for at least 12 consecutive months during the 24-month follow-up period. A total of 44 patients were treated with Casgevy. Of the 31 patients with sufficient follow-up time to be evaluable, 29 (93.5%) achieved this outcome. All treated patients achieved successful engraftment with no patients experiencing graft failure or graft rejection.

Indication 2 - transfusion-dependent beta thalassemia

approved January of 2024

The FDA approval of Casgevy was based on an ongoing open-label, multi-center, single-arm trial to evaluate the safety and efficacy of Casgevy in adult and adolescent patients with transfusion-dependent β-thalassemia. Eligible patients underwent mobilization and apheresis to collect CD34+ stem cells for Casgevy manufacture, followed by myeloablative conditioning and infusion of Casgev. Patients were then followed in Trial 2 for 24 months after Casgevy infusion. 

At the time of the interim analysis, a total of 59 patients enrolled in the trial, of which 59 (100%) patients started mobilization. A total of 52 (88%) patients received Casgevy infusion and formed the full analysis set (FAS). Thirty-five patients from the FAS (67%) had adequate follow-up to allow evaluation of the primary efficacy endpoint and formed the primary efficacy set (PES).

The median follow-up was 23.8 months from the time of Casgevy infusion in the PES. There were no cases of graft failure or graft rejection. The primary outcome was the proportion of patients achieving transfusion independence for 12 consecutive months (TI12), defined as maintaining weighted average Hb ≥9 g/dL without RBC transfusions for at least 12 consecutive months any time within the first 24 months after Casgevy infusion, evaluated starting 60 days after the last RBC transfusion for post-transplant support or TDT disease management.

The TI12 responder rate was 32/35 (91.4%). All patients who achieved TI12 remained transfusion-independent, with a median duration of transfusion-independence of 20.8 months and normal mean weighted average total Hb levels The median time to last RBC transfusion for patients who achieved TI12 was 30 days following Casgevy infusion.