Exagamglogene Autotemcel

Exagamglogene Autotemcel is a prescription medication indicated for the treatment of sickle cell disease in patients aged 12 years and older with recurrent vaso-occlusive events.

• Exagamglogene Autotemcel is available under the following different brand names: Casgevy.

Common side effects of Exagamglogene Autotemcel include:

• low levels of platelets and white blood cells
• mouth sores 
• nausea
• musculoskeletal pain
• abdominal pain
• vomiting
• febrile neutropenia (fever and low white blood cell count)
• headache
• itching

Serious side effects of Exagamglogene Autotemcel include:

• not available

Rare side effects of Exagamglogene Autotemcel include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Injection, suspension

• Supplied in 1 vial and more containing a frozen suspension of genome-edited autologous CD34+ cells in a cryopreservative medium containing 5% dimethyl sulfoxide (DMSO) and dextran 40
• One carton contains a single lot consisting of 1-9 vials
• A single dose may consist of multiple lots and therefore may consist of multiple cartons
• Lot Information Sheet listing the total dose is affixed inside the shipper

Sickle cell disease

Adult and pediatric dosage

• For autologous use only as a one-time, single-dose IV infusion
• Minimum recommended dose: 3 x 106 CD34+ cells/kg IV via central venous catheter following myeloablative conditioning

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Exagamglogene Autotemcel has severe interactions with no other drugs
• Exagamglogene Autotemcel has serious interactions with the following drugs:
  • crizanlizumab
  • deferasirox
  • deferiprone
  • deferoxamine
  • efbemalenograstim alfa
  • eflapegrastim
  • epoetin alfa
  • filgrastim
  • hydroxyurea
  • pegfilgrastim
  • voxelotor
• Exagamglogene Autotemcel has moderate interactions with no other drugs
• Exagamglogene Autotemcel has minor interactions with at least 21 other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Exagamglogene Autotemcel?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Exagamglogene Autotemcel?”

Cautions

• Potential neutrophil engraftment failure
  • Neutrophil engraftment failure is a potential risk in hematopoietic stem cell transplant (HSCT), defined as not achieving neutrophil engraftment after infusion and requiring the use of unmodified rescue CD34+ cells
  • In a clinical trial, all treated patients achieved neutrophil engraftment and no patients received rescue CD34+ cells
  • Monitor absolute neutrophil counts (ANC) and manage infections according to standard guidelines and medical judgment
  • In the event of neutrophil engraftment failure, infuse rescue CD34+ cells
• Prolonged time to platelet engraftment
  • Longer median platelet engraftment times were observed compared to allogeneic HSCT
  • There is an increased risk of bleeding until platelet engraftment is achieved
  • In a clinical trial, there was no association observed between the incidence of serious bleeding and time to platelet engraftment
  • Monitor for bleeding according to standard guidelines and medical judgment
  • Conduct frequent platelet counts until platelet engraftment and platelet recovery are achieved
  • Perform blood cell counts and other appropriate tests whenever clinical symptoms suggestive of bleeding arise
• Hypersensitivity reactions
  • Hypersensitivity reactions, including anaphylaxis, can occur due to dimethyl sulfoxide (DMSO) or dextran 40 in the cryopreservative solution
  • Monitor for hypersensitivity reactions during and after infusion
• Off-target genome editing risk
  • Off-target genome editing was not observed in the edited CD34+ cells evaluated from healthy donors and patients
  • However, the risk of unintended, off-target editing in an individual’s CD34+ cells cannot be ruled out due to genetic variants
  • Clinical significance of potential off-target editing is unknown
• Drug interaction overview
• Not expected to interact with hepatic cytochrome P-450 enzymes or drug transporters
• Granulocyte-colony stimulating factor (G-CSF)
  • G-CSF must not be used for CD34+ HSC mobilization of patients with sickle cell disease
• Hydroxyurea
  • Discontinue hydroxyurea at least 8 weeks before starting each mobilization cycle and conditioning
  • There is no experience regarding the use of hydroxyurea after Exagamglogene Autotemcel infusion
• Voxelotor and crizanlizumab
  • Discontinue voxelotor and crizanlizumab at least 8 weeks before mobilization and conditioning
  • Interaction potential with mobilization and myeloablative conditioning agents is unknown
• Iron chelators
  • Discontinue iron chelators at least 7 days before the initiation of myeloablative conditioning, due to potential interaction with the conditioning agent
  • Some iron chelators are myelosuppressive
  • If iron chelation is required, avoid using non-myelosuppressive iron chelators for at least 3 months and use myelosuppressive iron chelators for at least 6 months after Exagamglogene Autotemcel infusion
  • Phlebotomy can be used instead of iron chelation, when appropriate
• Live vaccines
  • Safety of immunization with live viral vaccines during or following Exagamglogene Autotemcel treatment has not been studied

Pregnancy and Lactation

• There are no clinical data regarding the use of Exagamglogene Autotemcel in pregnant women
• No animal reproductive and developmental toxicity studies have been conducted
• Must not be administered during pregnancy owing to risks associated with myeloablative conditioning
• Discuss pregnancy after infusion with the treating physician
• Pregnancy testing
  • Confirm a negative serum pregnancy test before the start of each mobilization cycle
  • Reconfirm negative test before myeloablative conditioning
• Contraception
  • There are insufficient exposure data to provide precise recommendations on the duration of contraception following treatment
  • Women of childbearing potential and men capable of fathering a child must use effective methods of contraception from the start of mobilization through at least 6 months after administration
• Infertility
  • Data are unavailable regarding the effects on human fertility
  • Effects on male and women fertility have not been evaluated in animal studies
  • Infertility has been observed with myeloablative conditioning therefore, advise patients regarding fertility preservation options before treatment, if appropriate
• Lactation
  • There are no data regarding the presence of Exagamglogene Autotemcel in human or animal milk, its effects on breastfed children, or its effects on milk production
  • Discontinued breastfeeding during myeloablative conditioning
  • Discuss breastfeeding after infusion with the treating physician