Casgevy (exagamglogene autotemcel)

It isessential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

For autologous use only. IV use only.

*Patients are required to undergo hematopoietic stem cell (HSC) mobilization followed by apheresis to obtain CD34+ cells for exagamglogene autotemcel manufacturing.

*Exagamglogene autotemcel must be administered between 48 hours and 7 days after the last dose of the myeloablative conditioning.

*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 exagamglogene autotemcel.

*Do not use an in-line blood filter or infusion pump when infusing exagamglogene autotemcel.

*Administer each vial of exagamglogene autotemcel via IV infusion within 20 minutes of thaw. A patient's dose may consist of multiple vials; all vials must be administered and the entire volume of each vial provided should be infused.

Dosing of exagamglogene autotemcel is based on body weight. The minimum recommended dose in adolescents >=12 years of age is 3 x 106 CD34+ cells/kg.

Dosing of exagamglogene autotemcel is based on body weight. The minimum recommended dose in adults is 3 x 106 CD34+ cells/kg.

No dosing information is available for this tab.

No dosing information is available for this tab.

No dosing information is available for this tab.

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Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Exagamglogene Autotemcel/Disease Modifying Agents

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: The interaction potential of disease modifying agents with exagamglogene autotemcel is unknown.(1)

CLINICAL EFFECTS: Disease modifying agents may interfere with exagamglogene autotemcel therapy.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Discontinue disease modifying therapies for sickle cell disease (e.g. voxelotor, crizanlizumab) at least 8 weeks prior to the start of mobilization.(1) It is recommended that patients be transfused at least 8 weeks prior to the initiation of myeloablative conditioning. At initiation of red blood cell exchange or simple transfusions, discontinue disease modifying therapies for sickle cell disease (e.g. voxelotor, crizanlizumab).(1)

DISCUSSION: There is no experience with the use of disease modifying agents with exagamglogene autotemcel infusion.(1)

Exagamglogene Autotemcel/Hydroxyurea

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Hydroxyurea may interfere with hematopoietic stem cell (HSC) mobilization of CD34+ cells.(1)

CLINICAL EFFECTS: Use of hydroxyurea before mobilization may result in unsuccessful stem cell mobilization and interfere with lovotibeglogene autotemcel therapy.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Discontinue disease modifying therapies for sickle cell disease (e.g., hydroxyurea) 8 weeks before each mobilization cycle.(1) It is recommended that patients be transfused at least 8 weeks prior to the initiation of myeloablative conditioning. At initiation of red blood cell exchange or simple transfusions, discontinue disease modifying therapies for sickle cell disease (e.g., hydroxyurea).(1)

DISCUSSION: Hydroxyurea may interfere with the manufacturing and effectiveness of exagamglogene autotemcel therapy. There is no experience with the use of hydroxyurea after exagamglogene autotemcel infusion.(1)

Exagamglogene Autotemcel/Iron Chelators

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Treatment with exagamglogene autotemcel requires hematopoietic stem cell (HSC) mobilization which can suppress the immune system.

CLINICAL EFFECTS: Iron chelators should be held prior to and after infusion with exagamglogene autotemcel.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Iron chelators should be discontinued 7 days prior to initiation of mobilization or conditioning. Avoid myelosuppressive iron chelators for six months after exagamglogene autotemcel infusion. Avoid non-myelosuppressive iron chelators for three months after exagamglogene autotemcel infusion. If iron chelation is needed, consider phlebotomy in lieu of iron chelation when appropriate.(1)

DISCUSSION: In preparation for infusion of exagamglogene autotemcel, iron chelation should be discontinued 7 days prior to initiation of mobilization or conditioning.(1)

Exagamglogene Autotemcel/Myelosuppressive Iron Chelators

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Treatment with exagamglogene autotemcel requires hematopoietic stem cell (HSC) mobilization which can suppress the immune system.

CLINICAL EFFECTS: Myelosuppressive iron chelators may result in increased risk of serious infections.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Iron chelators should be discontinued 7 days prior to initiation of mobilization or conditioning. Avoid myelosuppressive iron chelators for six months after exagamglogene autotemcel infusion. Avoid non-myelosuppressive iron chelators for three months after exagamglogene autotemcel infusion. If iron chelation is needed, consider phlebotomy in lieu of iron chelation when appropriate.(1)

DISCUSSION: In preparation for infusion of exagamglogene autotemcel, iron chelation should be discontinued 7 days prior to initiation of mobilization or conditioning.(1) In clinical trials, 100% of 44 patients experienced Grade 3 or 4 neutropenia from Day 1 to Month 24.(1)

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*None.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

• No disease contraindications

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.

More Frequent

• Anemia
• Hypoxia
• Neutropenic disorder
• Thrombocytopenic disorder

Less Frequent

• Biliary calculus
• Hemophagocytic lymphohistiocytosis
• Intracerebral hemorrhage

Rare or Very Rare

• Anaphylaxis
• Engraftment syndrome
• Hepatic veno-occlusive disease
• Nausea
• Non-cardiac chest pain
• Vomiting

More Frequent

• Anorexia
• Leukopenia
• Lymphopenia
• Pain in oropharynx
• Stomatitis
• Upper respiratory infection
• Viral infection

Less Frequent

• Acute abdominal pain
• Cd4 T lymphocyte deficiency
• Chills
• Constipation
• Epistaxis
• Fever
• Hyperbilirubinemia
• Musculoskeletal pain
• Prolonged activated partial thromboplastin time
• Pruritus of skin
• Tachycardia

Rare or Very Rare

• Pneumonia
• Sepsis

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The safety and efficacy of exagamglogene autotemcel have been established in pediatric patients with SCD and TDT who are 12 years of age and older. Use of exagamglogene autotemcel in patients 12 to less than 18 years of age is supported by data in 12 patients with SCD in Trial 1 (6 patients evaluable for the primary efficacy analysis), and 18 patients with TDT in Trial 2 (11 patients evaluable for the primary efficacy analysis). The efficacy and safety profile of exagamglogene autotemcel in pediatric patients 12 years of age and older were consistent with the efficacy and safety in adult patients.

Patients with SCD: The median (min, max) time to platelet engraftment was 45 (23, 81) days in pediatric patients 12 years of age and older and 32 (23, 126) days in adult patients. The median (min, max) time to neutrophil engraftment was 28 (24, 40) days in pediatric patients 12 years of age and older and 26 (15, 38) days in adult patients.

Patients with TDT: The median (min, max) time to platelet engraftment was 45 (20, 199) days in pediatric patients aged 12 years and older and 41.5 (24, 200) days in adult patients. The median (min, max) time to neutrophil engraftment was 30 (19, 56) days in pediatric patients aged 12 years and older and 28.5 (12, 40) days in adult patients.

The safety and efficacy of exagamglogene autotemcel in pediatric patients younger than 12 years of age have not been established.

There are no clinical data from the use of exagamglogene autotemcel in pregnant women. No animal reproductive and developmental toxicity studies have been conducted with exagamglogene autotemcel to assess whether it can cause fetal harm when administered to a pregnant woman. Exagamglogene autotemcel must not be administered during pregnancy because of the risks associated with myeloablative conditioning. Pregnancy after exagamglogene autotemcel infusion should be discussed with the treating physician.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

There are no data on the presence of exagamglogene autotemcel in human or animal milk, the effects on the breastfed child, or the effects on milk production. Because of the potential risks associated with myeloablative conditioning, breastfeeding should be discontinued during conditioning. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for exagamglogene autotemcel and any potential adverse effects on the breastfed child from exagamglogene autotemcel or from the underlying maternal condition. Breastfeeding after exagamglogene autotemcel infusion should be discussed with the treating physician.

Exagamglogene autotemcel has not been studied in patients >65 years of age. HSC transplantation must be appropriate for a patient to be treated with exagamglogene autotemcel.