Zynteglo

Zynteglo is an FDA-registered drug product whose active ingredient is BETIBEGLOGENE AUTOTEMCEL. It is labelled by Genetix Biotherapeutics Inc. taken by intravenous and marketed as a cellular therapy product. Identifiers on file: NDC 73554-3111, application BLA125717, label effective 20260721. This page reproduces the FDA-approved label text so you can check what a product is, who makes it and how it is supplied before discussing it with a pharmacist or prescriber.

Across FDA labelling, products containing BETIBEGLOGENE AUTOTEMCEL are most often described in connection with: treatment adult, pediatric patients, require regular, red blood, cell rbc, usage zynteglo, autologous hematopoietic, stem cell-based. Wording differs between labels, and the full indications section on this page takes precedence when it is present.

1 INDICATIONS AND USAGE 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. ( 1 )

2 DOSAGE AND ADMINISTRATION 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. It is recommended that patients be maintained at a hemoglobin (Hb) ≥ 11 g/dL for at least 30 days prior to mobilization and 30 days prior to myeloablative conditioning. Granulocyte-colony stimulating factor (G-CSF) and plerixafor were used for mobilization and busulfan was used for myeloablative conditioning. Refer to the prescribing information for the mobilization agent(s) and the myeloablative conditioning agent(s) prior to treatment. Perform screening for hepatitis B virus (HBV), hepatitis C virus (HCV), human T-lymphotrophic virus 1 & 2 (HTLV-1/HTLV-2), and human immunodeficiency virus 1 & 2 (HIV-1/HIV-2) in accordance with clinical guidelines before collection of cells for manufacturing. Mobilization and Apheresis Patients are required to undergo HSC mobilization followed by apheresis to obtain CD34+ cells for product manufacturing. The target number of CD34+ cells to be collected is ≥ 12 × 10 6 CD34+ cells/kg. If the minimum dose of 5.0 × 10 6 CD34+ cells/kg is not met, the patient may undergo additional cycles of mobilization and apheresis, separated by at least 14 days, in order to obtain more cells for additional manufacture. Up to two drug product lots may be administered to meet the target dose. A back-up collection of CD34+ cells of ≥ 1.5 × 10 6 CD34+ cells/kg (if collected by apheresis) or > 1.0 × 10 8 TNC/kg (Total Nucleated Cells, if collected by bone marrow harvest) is required. These cells must be collected from the patient and be cryopreserved prior to myeloablative conditioning. The back-up collection may be needed for rescue treatment if there is: 1) compromise of hematopoietic stem cells or ZYNTEGLO before infusion, 2) primary engraftment failure, or 3) loss of engraftment after infusion with ZYNTEGLO. Myeloablative Conditioning Full myeloablative conditioning must be administered before infusion of ZYNTEGLO. Consult prescribing information for the myeloablative conditioning agent(s) prior to treatment. Stop iron chelation at least 7 days prior to myeloablative conditioning. Prophylaxis for hepatic veno-occlusive disease (VOD) is recommended [see Clinical Studies (14) ] . Prophylaxis for seizures should be considered, as appropriate. Do not begin myeloablative conditioning until the complete set of infusion bag(s) constituting the dose of ZYNTEGLO has been received and stored at the treatment center and the availability of the back-up collection is confirmed. After completion of the myeloablative conditioning, allow a minimum of 48 hours of washout before ZYNTEGLO infusion. Receipt and Storage of ZYNTEGLO ZYNTEGLO is shipped to the treatment center in the vapor phase of liquid nitrogen shipper. Confirm patient identifiers on the product label(s) and Lot Information Sheet within the shipper. If there are any concerns about the product or packaging upon receipt, contact Genetix Biotherapeutics at 1-833-999-6378. Keep the infusion bag(s) in the metal cassette(s) and transfer ZYNTEGLO from the vapor phase of liquid nitrogen shipper to the treatment center vapor phase of liquid nitrogen storage at ≤ -140°C (≤ -220°F). Store in the vapor phase of liquid nitrogen at ≤ -140°C (≤ -220°F) until ready for thaw and administration. Preparation of ZYNTEGLO for Infusion Coordinate the timing of ZYNTEGLO thaw and infusion. Confirm the infusion time in advance and adjust the start time of ZYNTEGLO thaw such that it will be available for infusion when the patient and healthcare providers are ready. 1. Remove each metal cassette from liquid nitrogen storage and remove each infusion bag from the metal cassette. 2. Confirm that ZYNTEGLO is printed on the infusion bag(s). 3. Confirm that patient identity matches the unique patient identifiers located on the ZYNTEGLO infusion bag(s). Do not infuse ZYNTEGLO if the information on the patient-specific label on the infusion bag does not match the intended patient, and contact Genetix Biotherapeutics at 1-833-999-6378. 4. Ensure the correct number of infusion bags are present. Use the accompanying Lot Information Sheet to confirm that each infusion bag is within the expiration date. 5. Inspect each infusion bag for any breaches of integrity before thawing and infusion. If an infusion bag is compromised, follow the local guidelines and contact Genetix Biotherapeutics immediately at 1-833-999-6378. 6. If more than one infusion bag is provided, thaw and administer each infusion bag completely before proceeding to thaw the next infusion bag. 7. Thaw ZYNTEGLO at 37°C (98.6°F) in a water bath or dry bath. Thawing of each infusion bag takes approximately 2 to 4 minutes. Do not leave ZYNTEGLO unattended. Do not submerge the infusion ports in a water bath. 8. After thaw, mix the contents gently by massaging the infusion bag to disperse clumps of cellular material until all of the contents are uniform. If visible cell clumps remain, continue to gently mix the contents of the bag. Most small clumps of cellular material should disperse with gentle manual mixing. Do not filter, wash, spin down and/or resuspend ZYNTEGLO in new media prior to infusion. 9. Do not sample, alter, irradiate or refreeze ZYNTEGLO. 2.3 Administration ZYNTEGLO is for autologous use only. The patient's identity must match the patient identifiers on the ZYNTEGLO cassette(s) and infusion bag(s). Do not infuse ZYNTEGLO if the information on the patient-specific label does not match the intended patient. Product must be administered within 4 hours after thawing. Do not use an in-line blood filter or an infusion pump. 1. Before infusion, confirm that the patient's identity matches the unique patient identifiers on the ZYNTEGLO infusion bag(s). Use the Lot Information Sheet to confirm the total number of infusion bags to be administered. 2. Expose the sterile port on the infusion bag by tearing off the protective wrap covering the port. 3. Access the infusion bag and infuse ZYNTEGLO as soon as possible after thawing and complete the infusion within 4 hours. 4. Administer each infusion bag of ZYNTEGLO via intravenous infusion over a period of less than 30 minutes. If more than one infusion bag is provided, administer each infusion bag completely before proceeding to thaw and infuse the next infusion bag. 5. Flush all ZYNTEGLO remaining in the infusion bag(s) and any associated tubing with at least 50 mL of 0.9% sodium chloride solution to ensure that as many cells as possible are infused into the patient. After ZYNTEGLO Administration Standard procedures for patient management after HSC transplantation should be followed after ZYNTEGLO infusion. Irradiate any blood products required within the first 3 months after ZYNTEGLO infusion. Granulocyte-colony stimulating factor (G-CSF) is not recommended for 21 days after ZYNTEGLO infusion. Restarting iron chelation after ZYNTEGLO infusion may be necessary and should be based on clinical practice [see Drug Interactions (7.3) and Clinical Studies (14) ] . Phlebotomy can be used in lieu of iron chelation, when appropriate. Patients should not donate blood, organs, tissues, or cells at any time in the future. ZYNTEGLO contains human blood cells that are genetically modified with replication-incompetent, self-inactivating lentiviral vector. Follow universal precautions and biosafety guidelines (Biosafety Level 2) for handling and disposal of ZYNTEGLO to avoid potential transmission of infectious diseases.

4 CONTRAINDICATIONS None. None. ( 4 )

6 ADVERSE REACTIONS 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) ]. The median (min, max) age across the trials was 13 (4, 34) years; 49% were females; 49% were Asian, 44% White, 5% Other, 2% Not Reported. The median (min, max) duration of follow-up was 27.2 (4.1, 48.2) months. In the two trials, serious adverse reactions occurred in 37% of patients as of last follow-up. The most common serious adverse reactions (> 3%) were pyrexia (fever), thrombocytopenia, liver veno-occlusive disease, febrile neutropenia, neutropenia, and stomatitis. There were no deaths. The most common adverse reactions (≥ 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). Table 1 presents the non-laboratory treatment emergent adverse reactions reported in at least 10% of patients and Table 2 describes the laboratory abnormalities of Grade 3 or 4 that occurred in at least 10% of patients. Table 1: Summary of Non-Laboratory Treatment Emergent Adverse Reactions in at Least 10% of Patients; Day 1 – Month 24 After ZYNTEGLO Administration Includes adverse events associated with busulfan myeloablative conditioning. (N = 41) Adverse Reaction % Any Grade % Grade 3 or Higher Blood and lymphatic system disorders Febrile neutropenia 51 51 Gastrointestinal disorders Mucositis Mucositis includes anal inflammation, mucosal inflammation, oral mucosal exfoliation, oral mucosal roughening, pharyngeal inflammation, stomatitis. Encompasses more than one system organ class. 95 63 Vomiting 49 0 Abdominal pain Abdominal pain includes abdominal pain, abdominal pain lower, abdominal discomfort, abdominal pain upper. 39 2 Diarrhea 27 0 Nausea 24 2 Constipation 24 0 Dyspepsia 10 5 Gingival bleeding 10 2 General disorders and administration site conditions Pyrexia 49 12 Fatigue 12 0 Hepatobiliary disorders Venoocclusive liver disease 10 7 Infections and infestations Viral infection Viral infection includes BK virus infection, human rhinovirus test positive, influenza, influenza like illness, parainfluenza virus infection, rhinovirus infection, SARS-CoV-2 test positive, viral infection. 17 2 Upper respiratory tract infections Upper respiratory tract infections include upper airway cough syndrome, upper respiratory tract infection, viral upper respiratory tract infection, pharyngitis, pharyngitis streptococcal. 15 0 Nasopharyngitis 12 0 Sepsis Sepsis includes bacterial sepsis, neutropenic sepsis, fungal sepsis, sepsis. 10 10 Injury, poisoning and procedural complications Procedural pain 15 0 Transfusion reaction 15 0 Metabolism and nutrition disorders Decreased appetite 24 15 Musculoskeletal and connective tissue disorders Musculoskeletal pain Musculoskeletal pain includes musculoskeletal pain, musculoskeletal chest pain, bone pain, musculoskeletal discomfort, chest pain, myalgia, neck pain, non-cardiac chest pain, pain in extremity, spinal pain, tendon pain, back pain. 37 0 Nervous system disorders Headache Headache includes headache, migraine. 29 0 Respiratory, thoracic and mediastinal disorders Epistaxis 42 20 Cough Cough includes cough, upper-airway cough syndrome, productive cough. 34 0 Oropharyngeal pain Oropharyngeal pain includes oropharyngeal pain, oral pain, oropharyngeal discomfort, jaw pain. 15 0 Dyspnea 12 0 Hypoxia 12 7 Rhinitis Rhinitis includes rhinitis, rhinorrhea, rhinitis allergic. 12 0 Skin and subcutaneous tissue disorders Alopecia 44 0 Rash Rash includes acne, dermatitis acneiform, dermatitis atopic, macule, petechiae, rash, rash follicular, rash macular, rash maculo-papular, rash pruritic, rash pustular, rash vesicular. 27 0 Pigmentation disorder Pigmentation disorder includes oral pigmentation, pigmentation disorder, skin hyperpigmentation, skin hypopigmentation. 24 0 Pruritus 22 0 Vascular disorders Hypertension 10 0 Other clinically important adverse reactions that occurred in less than 10% of patients include the following: Cardiac disorders: congestive heart failure (2%) Hepatobiliary disorders: Serious hepatic veno-occlusive disease (VOD) occurred in 3 (7%) patients; of these three, two had not received prophylaxis for VOD. All patients who experienced serious VOD received treatment with defibrotide and recovered. Patients with β-thalassemia requiring regular transfusions may be at an increased risk of VOD following myeloablative conditioning. 1 Infections and infestations : pneumonia (7%) Infusion-related reaction including abdominal pain (7%) and tachycardia (2%). Table 2: Grade 3 or 4 Treatment Emergent Laboratory Abnormalities Occurring in ≥ 10% of Patients Following Treatment with ZYNTEGLO Includes lab abnormalities associated with busulfan myeloablative conditioning. from Day 1 to Month 24 (N = 41) The denominator is 36 for hyperglycemia, due to missing data. Laboratory Abnormality Baseline lab values were assessed prior to apheresis. Grade 3 or 4 (%) Abbreviations: ALT: alanine aminotransferase Neutropenia 100 Thrombocytopenia 100 Leukopenia 100 Anemia 95 Lymphopenia 61 ALT Increased 24 Hypophosphatemia 20 Hyperglycemia 14 Hypokalemia 12 Hyperbilirubinemia 10 Hyponatremia 10 Platelet Engraftment Delay Platelet engraftment was defined as three consecutive platelet values ≥ 20,000 cells/microliter, obtained on different days after ZYNTEGLO infusion, with no platelet transfusions administered for 7 days immediately preceding and during the evaluation period. Forty-one patients treated with ZYNTEGLO achieved platelet engraftment by a median of Day 46 (range 20 - 94) in clinical studies. Patients without a spleen reached the criterion for platelet engraftment earlier as compared to patients with an intact spleen: median Day 42 (range, 21 - 53 days) vs. median Day 50 (range, 20 - 94 days), respectively. Patients achieving platelet engraftment at ≥ Day 46 did not have an increased incidence of bleeding compared with patients with platelet engraftment at < Day 46. Neutrophil Engraftment While all subjects achieved neutrophil engraftment after ZYNTEGLO in the clinical studies, 7% of patients remained dependent on G-CSF beyond Day 43, one through Day 77. G-CSF discontinuation was followed by transient decreases in neutrophil counts to < 500 cells/microliter after Day 43 in six (15%) patients.

What is Zynteglo used for?
1 INDICATIONS AND USAGE 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. ( 1 )

Who makes Zynteglo?
Genetix Biotherapeutics Inc. is the labeler of record for Zynteglo.

What form does Zynteglo come in?
administered by intravenous. Strengths and pack sizes vary by label, so compare the NDC on your pack with the identifier listed on this page.

Is Zynteglo prescription or over-the-counter?
The FDA label for this product is recorded as cellular therapy. Marketing status can differ between strengths and countries, so check the dispensing rules where you live.

Has Zynteglo been recalled?
No FDA recall record in our database matches this product name or manufacturer. Recall data is updated periodically, so a very recent notice may not appear here yet.

Where does this information come from?
All content is reproduced from FDA Structured Product Labelling data via openFDA. It is provided for identification and reference only and is not medical advice.