Betibeglogene Autotemcel

Betibeglogene Autotemcel is an autologous hematopoietic stem cell-based gene therapy indicated for the treatment of adult and pediatric patients with β-thalassemia who require regular red blood cell transfusions.

• Betibeglogene Autotemcel is available under the following different brand names: Zynteglo

Common side effects of Betibeglogene Autotemcel include:

• inflammation of mucus membranes
• febrile neutropenia
• vomiting
• fever
• hair loss
• nosebleed
• abdominal pain
• musculoskeletal pain
• cough
• headache
• diarrhea
• rash
• constipation
• nausea
• decreased appetite
• pigmentation disorder
• itching
• anemia
• low blood platelets (thrombocytopenia)
• low white blood cells (neutropenia, leukopenia, lymphopenia)

Serious side effects of Betibeglogene Autotemcel include:

• hives
• rash
• itching
• swelling of the lips, tongue, or throat
• shortness of breath or difficulty breathing
• unusual bruising or bleeding
• nose bleeding
• severe headache
• blood in urine
• stool, or vomit
• coughing up blood
• unusual abdominal or back pain
• fever
• sore throat
• ongoing cough
• congestion

Rare side effects of Betibeglogene 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

Cell suspension for IV infusion

• Contains a minimum of 5 × 106 CD34+ cells/kg (body weight) in 1 and more infusion bags.
• See the Lot Information Sheet provided with product shipment for additional information about the dose.

Transfusion-dependent beta thalassemia

Adult and pediatric dosage

• Minimum recommended dose: 5 × 106 CD34+ cells/kg as a one-time IV infusion
• Provided as a single dose for infusion containing a suspension of CD34+ cells in more than1 infusion bag
• Before Betibeglogene Autotemcel infusion
  • Before initiating mobilization, apheresis, and myeloablative conditioning, confirm that hematopoietic stem cell (HSC) transplantation is appropriate for the patient
  • Maintain Hgb 11 g/dL and above for at least 30 days before mobilization and 30 days before myeloablative conditioning
  • In clinical trials, granulocyte-colony stimulating factor and plerixafor were used for mobilization, and busulfan was used for myeloablative conditioning; refer to the prescribing information for mobilization agent(s) and myeloablative conditioning agent(s) before treatment
  • Screen for hepatitis B virus, hepatitis C virus, human T-lymphotropic virus 1 and 2 (HTLV-1/HTLV-2), and HIV-1/HIV-2 according to clinical guidelines before cell collection for manufacturing
• Mobilization and apheresis
  • HSC mobilization is required, followed by apheresis to obtain CD34+ cells for product manufacturing
  • Target number of CD34+ cells to be collected is ≥12 × 106 CD34+ cells/kg
  • If the minimum dose (5 × 106 CD34+ cells/kg) is not met, the patient may undergo additional cycles of mobilization and apheresis, separated by at least 14 days, to obtain more cells for additional manufacture
  • Up to 2 drug product lots may be administered to meet the target dose
  • A backup collection of CD34+ cells of 1.5 × 106 CD34+ cells/kg and above (if collected by apheresis) or above 1x 108 TNC/kg (Total Nucleated Cells, if collected by bone marrow harvest) is required; these cells must be collected from the patient and be cryopreserved before myeloablative conditioning
  • May need a backup collection for rescue treatment if there is
  • Compromise of HSCs or Betibeglogene Autotemcel before infusion
• Primary engraftment failure
  • Loss of engraftment after infusion with Betibeglogene Autotemcel
• Myeloablative conditioning
  • Full myeloablative conditioning must be administered before Betibeglogene Autotemcel infusion
  • Refer to the prescribing information for myeloablative conditioning agent(s) before treatment
  • Stop iron chelation at least 7 days before myeloablative conditioning
  • Prophylaxis for hepatic veno-occlusive disease (VOD) is recommended
  • Consider prophylaxis for seizures, as appropriate
  • Do not begin myeloablative conditioning until a complete set of infusion bag(s) constituting the full dose of Betibeglogene Autotemcel is received and stored at the treatment center and the availability of backup collection is confirmed
  • After completion of the myeloablative conditioning, allow at least 48 hours of washout before Betibeglogene Autotemcel infusion

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.

• Betibeglogene Autotemcel has severe interactions with no other drugs.
• Betibeglogene Autotemcel has serious interactions with at least 36 other drugs.
• Betibeglogene Autotemcel has moderate interactions with the following drugs:
  • adenovirus types 4 and 7 live, oral
  • BCG vaccine live
  • cholera vaccine
  • dengue vaccine
  • Ebola Zaire vaccine
  • influenza virus vaccine quadrivalent, intranasal
  • measles (rubeola) vaccine
  • measles mumps and rubella vaccine, live
  • measles, mumps, rubella, and varicella vaccine, live
  • poliovirus vaccine live oral trivalent
  • rotavirus oral vaccine, live
  • rubella vaccine
  • smallpox (vaccinia) and monkeypox vaccine, live, nonreplicating
  • smallpox (vaccinia) vaccine, attenuated
  • smallpox (vaccinia) vaccine, live
  • typhoid polysaccharide vaccine
  • typhoid vaccine live
  • varicella virus vaccine live
  • yellow fever vaccine
  • zoster vaccine live
• Betibeglogene Autotemcel has minor interactions with no 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 Betibeglogene Autotemcel?”

Long-Term Effects

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

Cautions

• Delayed platelet engraftment
  • Delayed platelet engraftment observed
  • Bleeding risk increases before platelet engraftment and may continue after engraftment in patients with prolonged thrombocytopenia; 15% incidence of decreased platelets grade of  3 and more on or after day 100
  • Counsel patients on bleeding risk until platelet recovery is achieved; instruct patients to seek immediate attention for new or worsening bleeding or bruising
  • Monitor for thrombocytopenia and bleeding according to standard guidelines
  • Conduct frequent platelet counts until platelet engraftment and platelet recovery are achieved
  • Perform complete blood count (CBC) and other appropriate tests whenever clinical symptoms suggestive of bleeding arise
  • Risk of neutrophil engraftment failure
  • There is a potential risk for neutrophil engraftment failure after treatment
  • Neutrophil engraftment failure is defined as failure to achieve 3 consecutive absolute neutrophil counts (ANC) above 500 cells/μL obtained on different days by day 43 after infusion
  • Monitor neutrophil counts until engraftment is achieved
  • If neutrophil engraftment failure occurs, provide rescue treatment with the backup collection of CD34+ cells
• Risk of insertional oncogenesis
  • There is a potential risk for lentiviral vector (LVV)–mediated insertional oncogenesis after treatment
  • Patients may develop hematologic malignancies and should be monitored lifelong
  • Monitor for hematologic malignancies with CBC (with differential) at 6 and 12 months and then at least annually for and above 15 years after treatment, and integration site analysis at 6 and 12 months and as warranted
  • If malignancy occurs, contact bluebird bio at 1-833-999-6378 for reporting and to obtain instructions on the collection of samples for testing
• Hypersensitivity reactions
  • Allergic reactions, including anaphylaxis, may occur
  • Cell suspension contains dimethyl sulfoxide
  • Interference with serology testing
  • Patients who have received Betibeglogene Autotemcel are likely to test positive by polymerase chain reaction assays for HIV due to integrated BB305 LVV proviral DNA, resulting in a false-positive test for HIV
  • Use alternate tests
• Drug interaction overview
  • Vaccines
    • Follow institutional guidelines for vaccine administration
    • Safety of immunization with live viral vaccines during or following Betibeglogene Autotemcel treatment has not been studied
  • Antiretrovirals and hydroxyurea
    • Do not take antiretrovirals or hydroxyurea for at least 1 month before mobilization or the expected duration for elimination of the medications, and until all cycles of apheresis are completed
    • Antiretrovirals may interfere with the manufacturing of the apheresed cells
  • Iron chelation
    • Consider drug-drug interactions between iron chelators and myeloablative conditioning agents
    • Discontinue iron chelators at least 7 days before starting conditioning
    • Refer to the prescribing information for iron chelator(s) and the myeloablative conditioning agent for recommendations regarding coadministration with CYP3A substrates
    • Some iron chelators are myelosuppressive; after Betibeglogene Autotemcel infusion, avoid the use of these iron chelators for 6 months
    • If iron chelation is needed, consider the administration of non-myelosuppressive iron chelators
    • Phlebotomy can be used instead of iron chelation, when appropriate
  • Erythropoiesis-stimulating agents
    • No information available regarding the coadministration of erythropoiesis-stimulating agents with Betibeglogene Autotemcel

Pregnancy and Lactation

• Confirm negative serum pregnancy test before the start of mobilization and reconfirm before conditioning procedures and before Betibeglogene Autotemcel administration
• Data are not available regarding the administration of Betibeglogene Autotemcel to pregnant women; consider risks to pregnancy and fertility associated with myeloablative conditioning agents
• No reproductive and developmental toxicity studies in animals have been conducted
• Contraception
  • Data are insufficient to provide recommendations on the duration of contraception following treatment with Betibeglogene Autotemcel
  • Women of childbearing potential and men capable of fathering a child should use effective contraception (ie, IUD or combination of hormonal and barrier contraception) from the start of mobilization through at least 6 months after administration
  • Advise patients of the risks associated with conditioning agents
• Infertility
  • Data are unavailable regarding the effects of Betibeglogene Autotemcel on fertility
  • Data are available on infertility risk associated with myeloablative conditioning
  • Advise patients of the option to cryopreserve semen or ova before treatment, if appropriate
• Lactation
  • Data are not available regarding the presence of Betibeglogene Autotemcel in human milk and its effects on breastfed infants or milk production