Betibeglogene Autotemcel

ZYNTEGLO adds functional copies of a modified β-globin gene into patients' hematopoietic stem cells (HSCs) through transduction of autologous CD34+ cells with BB305 LVV. After ZYNTEGLO infusion, transduced CD34+ HSCs engraft in the bone marrow and differentiate to produce RBCs containing biologically active β A-T87Q -globin (a modified β-globin protein) that will combine with α-globin to produce functional adult Hb containing β A-T87Q -globin (HbA T87Q ).

• ZYNTEGLO is indicated for the treatment of adult and pediatric patients with β-thalassemia who require regular red blood cell (RBC) transfusions. ZYNTEGLO 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 (RBC) transfusions.

• None. None.contraindicated

For autologous use only. For one-time single-dose intravenous use only. 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 ZYNTEGLO manufacturing. ( 2.2 ) Dosing of ZYNTEGLO is based on the number of CD34+ cells in the infusion bag(s) per kg of body weight. ( 2.1 ) The minimum recommended dose is 5.0 × 10 6 CD34+ cells/kg. ( 2.1 ) Full myeloablative conditioning must be administered before infusion of ZYNTEGLO. ( 2.2 ) Prophylaxis for hepatic veno-occlusive disease (VOD) is recommended. Prophylaxis for seizures should be considered. ( 2.2 ) Verify that the patient's identity matches the unique patient identification information on the ZYNTEGLO infusion bag(s) prior to infusion. ( 2.2 ) Do not sample, alter, or irradiate ZYNTEGLO. ( 2.2 ) Do not use an in-line blood filter or an infusion pump. ( 2.3 ) Administer each infusion bag of ZYNTEGLO via intravenous infusion over a period of less than 30 minutes. ( 2.3 ) 2.1 Dose ZYNTEGLO is provided as a single dose for infusion containing a suspension of CD34+ cells in one or more infusion bags. The minimum recommended dose of ZYNTEGLO is 5.0 × 10 6 CD34+ cells/kg. See the Lot Information Sheet provided with the product shipment for additional information pertaining to dose. 2.2 Preparation Before ZYNTEGLO Infusion Before mobilization, apheresis, and myeloablative conditioning are initiated, confirm that hematopoietic stem cell (HSC) transplantation is appropriate for the patient.

Delayed Platelet Engraftment: Monitor platelet counts until platelet engraftment and recovery are achieved. Patients should be monitored for thrombocytopenia and bleeding. ( 5.1 ) Risk of Neutrophil Engraftment Failure: Monitor absolute neutrophil counts (ANC) after ZYNTEGLO infusion. If neutrophil engraftment does not occur administer rescue cells. ( 5.2 ) Risk of Insertional Oncogenesis: Monitor patients at least annually for hematologic malignancies for at least 15 years after ZYNTEGLO infusion. ( 5.3 ) Hypersensitivity Reactions: Monitor for hypersensitivity reactions during infusion. ( 5.4 ) 5.1 Delayed Platelet Engraftment Delayed platelet engraftment has been observed with ZYNTEGLO treatment. Bleeding risk is increased prior to platelet engraftment and may continue after engraftment in patients with prolonged thrombocytopenia; 15% of patients had ≥ Grade 3 decreased platelets on or after Day 100. Patients should be made aware of the risk of bleeding until platelet recovery has been achieved. Monitor patients for thrombocytopenia and bleeding according to standard guidelines. Conduct frequent platelet counts until platelet engraftment and platelet recovery are achieved. Perform blood cell count determination and other appropriate testing whenever clinical symptoms suggestive of bleeding arise. 5.2 Risk of Neutrophil Engraftment Failure There is a potential risk of neutrophil engraftment failure after treatment with ZYNTEGLO.

The following adverse reactions are described elsewhere in the labeling: Delayed Platelet Engraftment [see Warnings and Precautions (5.1) ] Risk of Neutrophil Engraftment Failure [see Warnings and Precautions (5.2) ] Risk of Insertional Oncogenesis [see Warnings and Precautions (5.3) ] Hypersensitivity Reactions [see Warnings and Precautions (5.4) ] The most common non-laboratory adverse reactions (incidence ≥ 20%) were mucositis, febrile neutropenia, vomiting, pyrexia (fever), alopecia (hair loss), epistaxis (nose bleed), abdominal pain, musculoskeletal pain, cough, headache, diarrhea, rash, constipation, nausea, decreased appetite, pigmentation disorder, and pruritus (itch). ( 6.1 ) The most common Grade 3 or 4 laboratory abnormalities (> 50%) include neutropenia, thrombocytopenia, leukopenia, anemia, and lymphopenia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Genetix Biotherapeutics at 1-833-999-6378 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety data described in this section reflect exposure to ZYNTEGLO in two open-label, single-arm clinical trials and one long-term follow-up study, in which 41 patients with β-thalassemia requiring regular transfusions were treated with ZYNTEGLO [see Clinical Studies (14) ].

8.1 Pregnancy Risk Summary There are no available data with ZYNTEGLO administration in pregnant women. Consider the risks associated with myeloablative conditioning agents on pregnancy and fertility. No reproductive and developmental toxicity studies in animals have been conducted with ZYNTEGLO to assess whether it can cause fetal harm when administered to a pregnant woman. It is not known whether ZYNTEGLO has the potential to be transferred to the fetus. Therefore, ZYNTEGLO should not be administered to women who are pregnant, and pregnancy after ZYNTEGLO infusion should be discussed with the treating physician. No nonclinical germline transmission studies have been conducted with ZYNTEGLO. 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. 8.2 Lactation Risk Summary There is no information regarding the presence of ZYNTEGLO in human milk, the effect on the breastfed infant, and the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for ZYNTEGLO and any potential adverse effects on the breastfed child from ZYNTEGLO.

Metabolism

ZYNTEGLO is an autologous gene therapy which includes hematopoietic stem cells (HSCs) that have been genetically modified ex vivo . The nature of ZYNTEGLO is such that conventional studies on pharmacokinetics, absorption, distribution, metabolism, and elimination are not applicable.

1. 1Epistaxis1633%
2. 2Endocrine Disorder1021%
3. 3Hypothalamo-pituitary Disorder1021%
4. 4Venoocclusive Liver Disease715%
5. 5Mucosal Inflammation48.3%
6. 6Platelet Count Decreased48.3%
7. 7Acute Myeloid Leukaemia36.3%
8. 8Haematemesis36.3%
9. 9Primary Hypogonadism36.3%
10. 10Pyrexia36.3%
11. 11Thrombocytopenia36.3%
12. 12Alopecia24.2%
13. 13Ascites24.2%
14. 14Bacteraemia24.2%
15. 15Cognitive Disorder24.2%

The 8 most recently updated of 8 ClinicalTrials.gov registrations naming Betibeglogene Autotemcel as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Study of Participants with Β-Thalassemia Treated with Betibeglogene Autotemcel
  Recruiting · Observational · 150 enrolled · Genetix Biotherapeutics Inc.
  NCT06271512updated 2025-02-11
• Study to Assess the Efficacy and Safety of CLBS12 in Patients with Critical Limb Ischemia (CLI)
  Completed · Phase 2 · Interventional · 33 enrolled · Lisata Therapeutics, Inc.
  NCT02501018updated 2024-10-09
• A Study Evaluating the Efficacy and Safety of the LentiGlobin® BB305 Drug Product in Participants With Transfusion-Dependent β-Thalassemia
  Completed · Phase 3 · Interventional · 19 enrolled · Genetix Biotherapeutics Inc.
  NCT03207009updated 2024-03-07
• A Study Evaluating the Efficacy and Safety of the LentiGlobin® BB305 Drug Product in Participants With Transfusion-Dependent β-Thalassemia, Who do Not Have a β0/β0 Genotype
  Completed · Phase 3 · Interventional · 24 enrolled · Genetix Biotherapeutics Inc.
  NCT02906202updated 2023-06-18
• Study of Intracoronary CD34+ Cell Administration in Patients With Early Coronary Atherosclerosis
  Completed · Phase 1 · Interventional · 21 enrolled · Mayo Clinic
  NCT03471611updated 2022-02-07
• Autologous Followed by Non-myeloablative Allogeneic Transplantation for Non-Hodgkin's Lymphoma
  Terminated · Phase 2 · Interventional · 50 enrolled · Stanford University
  NCT00481832updated 2018-02-14
• Peripheral Stem Cell Transplant in Treating Patients With Multiple Myeloma
  Completed · Phase 2 · Interventional · 60 enrolled · Alliance for Clinical Trials in Oncology
  NCT00028600updated 2016-07-04
• An Efficacy and Safety Study of Autologous Cluster of Differentiation 34 (CD34+) Hematopoietic Progenitor Cells Transduced With Placebo or an Anti- Human Immunodeficiency Virus Type 1 (HIV-1) Ribozyme (OZ1) in Participants With HIV-1 Infection
  Completed · Phase 2 · Interventional · 1 enrolled · Janssen-Cilag Pty Ltd
  NCT00074997updated 2016-06-20

Frequently asked questions

How does Betibeglogene Autotemcel work?

ZYNTEGLO adds functional copies of a modified β-globin gene into patients' hematopoietic stem cells (HSCs) through transduction of autologous CD34+ cells with BB305 LVV. After ZYNTEGLO infusion, transduced CD34+ HSCs engraft in the bone marrow and differentiate to produce RBCs containing biologically active β A-T87Q -globin (a modified β-globin protein) that will combine with α-globin to produce functional adult Hb containing β A-T87Q -globin (HbA T87Q ).

What is Betibeglogene Autotemcel used for?

According to FDA labeling, Betibeglogene Autotemcel carries indications including: ZYNTEGLO is indicated for the treatment of adult and pediatric patients with β-thalassemia who require regular red blood cell (RBC) transfusions. ZYNTEGLO 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 (RBC) transfusions.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Betibeglogene Autotemcel?

Betibeglogene Autotemcel is classified as Other hematological agents, Beta-globin Gene Transfer, Hemoglobin Function Restoration.

What are the brand names for Betibeglogene Autotemcel?

Betibeglogene Autotemcel is marketed under brand names including Zynteglo.

What are the contraindications for Betibeglogene Autotemcel?

Betibeglogene Autotemcel labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.