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Zynteglo is a brand name for Betibeglogene Autotemcel. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: 4.1 Therapeutic indication Zynteglo is indicated for the treatment of patients 12 years and older with transfusion-dependent β-thalassaemia (TDT) who do not have a β0/β0 genotype, for whom haematopoietic stem cell (HSC) transplantation is appropriate but a human leukocyte antigen (HLA)-matched related HSC donor is not…
Verbatim from this product's EMA label. Tap a section to expand.
Zynteglo must be administered in a qualified treatment centre by a physician(s) with experience in HSC transplantation and in the treatment of patients with TDT. Medicinal product no longer authorised3 Patients are expected to enrol in a registry and will be followed in the registry in order to better understand the long-term safety and efficacy of Zynteglo.
0 × 106 CD34+ cells/kg. In clinical studies doses up to 20 × 106 CD34+ cells/kg have been administered. The minimum recommended dose is the same for adults and adolescents 12 years of age and older. 4) and should only be administered once.
1 for a description of the mobilisation regimen used in clinical studies). The minimum target number of CD34+ cells to be collected is 12 × 106 CD34+ cells/kg. 0 × 106 CD34+ cells/kg is not met after initial medicinal product manufacturing, the patient may undergo one or more additional cycles of mobilisation and apheresis, separated by at least 14 days, in order to obtain more cells for additional manufacture.
0 × 108 TNC/kg (if collected by bone marrow harvest) is required. These cells must be collected from the patient and be cryopreserved prior to myeloablative conditioning and infusion with Zynteglo. 4). 4). 1 for a description of the myeloablative regimen used in clinical studies).
It is recommended that patients maintain haemoglobin (Hb) ≥11 g/dL for at least 30 days prior to mobilisation and during myeloablative conditioning. Iron chelation should be stopped at least 7 days prior to myeloablative conditioning.
Prophylaxis for hepatic veno-occlusive disease (VOD) is recommended. 1 for a description of the prophylaxis regimen used in clinical studies). Myeloablative conditioning should not begin until the complete set of infusion bag(s) constituting the dose of Zynteglo has been received and stored at the administration site, and the availability of the back-up collection is confirmed.
6 for details on Zynteglo administration and handling. After Zynteglo administration Any blood products required within the first 3 months after Zynteglo infusion should be irradiated. 1). Phlebotomy can be used in lieu of iron chelation, when appropriate.
Medicinal product no longer authorised4 Special populations Elderly Zynteglo has not been studied in patients >65 years of age. 4). No dose adjustment is required. Renal impairment Zynteglo has not been studied in patients with renal impairment.
Summary of the safety profile The safety of Zynteglo was evaluated in 45 patients with TDT. 2%). Given the small patient population and size of Medicinal product no longer authorised8 cohorts, adverse reactions in the table below do not provide a complete perspective on the nature and frequency of these events.
Tabulated list of adverse reactions Adverse reactions are listed by MedDRA body system organ class and by frequency convention. Frequencies are defined as: very common (≥1/10), and common (≥1/100 to <1/10). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.
Tables 1, 2, and 3 are lists of adverse reactions attributed to mobilisation/apheresis, myeloablative conditioning, and Zynteglo, respectively, experienced by patients with TDT in clinical trials with Zynteglo. Table 1 Adverse reactions attributed to mobilisation/apheresis System Organ Class (SOC) Very Common (≥10%) Common (≥1% - <10%) Blood and lymphatic system disorders Thrombocytopenia Splenomegaly, Leukocytosis Metabolism and nutrition disorders Hypocalcaemia Hypokalaemia, Hypomagnesaemia Psychiatric disorders Agitation Nervous system disorders Headache, Peripheral sensory neuropathy Dizziness, Head discomfort, Paraesthesia Cardiac disorders Cardiac flutter Vascular disorders Hypotension Respiratory, thoracic and mediastinal disorders Hypoxia, Epistaxis Gastrointestinal disorders Nausea Vomiting, Lip swelling, Abdominal pain, Abdominal pain upper, Paraesthesia oral Skin and subcutaneous tissue disorders Rash, Hyperhidrosis Musculoskeletal and connective tissue disorders Bone pain Back pain, Musculoskeletal discomfort General disorders and administration site conditions Pyrexia, Influenza like illness, Chest discomfort, Chest pain, Injection site reaction, Catheter site haemorrhage, Catheter site bruise, Injection site bruising, Fatigue, Non-cardiac chest pain, Catheter site pain, Injection site pain, Puncture site pain, Pain Investigations Blood magnesium decreased Injury, poisoning and procedural complications Citrate toxicity, Contusion, Procedural pain Medicinal product no longer authorised9 Table 2 Adverse reactions attributed to myeloablative conditioning SOC Very Common (≥10%) Common (≥1% - <10%) Infections and infestations Neutropenic sepsis, Systemic infection, Staphylococcal infection, Pneumonia, Lower respiratory tract infection, Urinary tract infection, Mucosal infection, Cellulitis, Vaginal infection, Rash pustular, Folliculitis, Gingivitis, Vulvovaginal candidiasis Blood and lymphatic system disorders Febrile neutropenia, Neutropenia, Thrombocytopenia, Leukopenia, Anaemia Lymphopenia, Leukocytosis, Monocyte count decreased, Neutrophilia, Mean cell haemoglobin concentration increased Endocrine disorders Primary hypogonadism Metabolism and nutrition disorders Decreased appetite Hypocalcaemia, Hypokalaemia, Metabolic acidosis, Fluid overload, Fluid retention, Hypomagnesaemia, Hyponatraemia, Hypophosphataemia, Hyperphosphataemia Psychiatric disorders Insomnia Anxiety Nervous system disorders Headache Dizziness, Lethargy, Dysgeusia, Ageusia, Memory impairment Eye disorders Conjunctival haemorrhage Ear and labyrinth disorders Vertigo Cardiac disorders Cardiac failure congestive, Atrial fibrillation Vascular disorders Hypotension, Haematoma, Hot flush Respiratory, thoracic and mediastinal disorders Epistaxis, Pharyngeal inflammation Hypoxia, Pulmonary mass, Dyspnoea, Pleural effusion, Rales, Upper-airway cough syndrome, Cough, Laryngeal pain, Hiccups, Oropharyngeal pain Gastrointestinal disorders Stomatitis, Vomiting, Nausea, Diarrhoea, Gingival bleeding, Constipation, Abdominal pain, Anal inflammation Anal haemorrhage, Gastritis, Gastrointestinal inflammation, Abdominal distension, Abdominal pain upper, Anal fissure, Dyspepsia, Dysphagia, Oesophagitis, Haemorrhoids, Proctalgia, Lip dry Hepatobiliary disorders Veno-occlusive liver disease, Alanine aminotransferase increased, Aspartate aminotransferase increased, Blood bilirubin increased Cholecystitis, Cholelithiasis, Hepatomegaly, Jaundice, Transaminases increased, Gamma-glutamyltransferase increased Skin and subcutaneous tissue disorders Alopecia, Pruritus, Skin hyperpigmentation Petechiae, Ecchymosis, Pain of skin, Palpable purpura, Pigmentation disorder, Pruritus Medicinal product no longer authorised10 SOC Very Common (≥10%) Common (≥1% - <10%) generalised, Purpura, Sweat gland disorder, Urticaria, Dry skin, Rash Musculoskeletal and connective tissue disorders Bone pain, Myalgia, Pain in extremity, Back pain Renal and urinary disorders Haematuria, Pollakiuria Reproductive system and breast disorders Vaginal haemorrhage Ovarian failure, Menstruation irregular, Premature menopause, Blood follicle stimulating hormone increased, Blood testosterone decreased General disorders and administration site conditions Pyrexia, Fatigue, Mucosal inflammation Face oedema, Hypothermia, Feeling cold, Pain, Xerosis Investigations C-reactive protein increased, Aspergillus test positive, Blood potassium decreased, Weight decreased, Blood alkaline phosphatase decreased, Blood magnesium decreased, Forced expiratory flow decreased, Protein total decreased, Blood albumin decreased, Reticulocyte count decreased, Reticulocyte percentage decreased Injury, poisoning and procedural complications Transfusion reaction, Skin abrasion Table 3 Adverse reactions attributed to Zynteglo SOC Very Common (≥10%) Common (≥1% - <10%) Blood and lymphatic system disorders Thrombocytopenia, Leukopenia, Neutropenia Vascular disorders Hot flush Respiratory, thoracic and mediastinal disorders Dyspnoea Gastrointestinal disorders Abdominal pain Musculoskeletal and connective tissue disorders Pain in extremity General disorders and administration site conditions Non-cardiac chest pain Description of selected adverse reactions Bleeding Bleeding is a potential complication of […]
Traceability The traceability requirements of cell-based advanced therapy medicinal products must apply. To ensure traceability the name of the product, the batch number and the name of the treated patient should be kept for a period of 30 years.
General Warnings and precautions of the mobilisation agents and the myeloablative conditioning agent must be considered. Patients treated with Zynteglo should not donate blood, organs, tissues or cells for transplantation at any time in the future.
This information is provided in the Patient Alert Card which must be given to the patient after treatment. Zynteglo is intended solely for autologous use and must not be administered to other patients. Confirm that the patient’s identity matches the unique patient identification information on the Zynteglo infusion bag(s) and metal cassette(s).
Do not infuse Zynteglo if the information on the patient specific label on the infusion bag(s) or metal cassette(s) do not match the intended patient. Risks associated with TDT and iron overload Patients with TDT experience iron overload due to chronic red blood cell (RBC) transfusions that can lead to end organ damage.
, patients with cardiac T2* <10 msec by magnetic resonance imaging (MRI). MRI of the liver should be performed on all patients prior to myeloablative conditioning. It is recommended that patients with MRI results demonstrating liver iron content ≥15 mg/g undergo liver biopsy for further evaluation.
If the liver biopsy demonstrates bridging fibrosis, cirrhosis, or active hepatitis, HSC transplantation with myeloablative conditioning is not appropriate. Risk of insertional oncogenesis No cases of myelodysplasia, leukaemia, or lymphoma have been reported in clinical studies with Zynteglo in patients with TDT.
There are no reports of LVV-mediated insertional mutagenesis resulting in oncogenesis after treatment with Zynteglo. Nevertheless, there is a theoretical risk of myelodysplasia, leukaemia, or lymphoma after treatment with Zynteglo. Patients should be monitored at least annually for myelodysplasia, leukaemia, or lymphoma (including with a complete blood count) for 15 years post treatment with Zynteglo.
1. 6). Previous treatment with HSC gene therapy. Contraindications to the mobilisation agents and the myeloablative conditioning agent must be considered. Medicinal product no longer authorised5
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73 m2 to ensure HSC transplantation is appropriate. No dose adjustment is required. Hepatic impairment Zynteglo has not been studied in patients with hepatic impairment. ). No dose adjustment is required. Paediatric population The safety and efficacy of Zynteglo in children <12 years of age have not yet been established.
Patients seropositive for human immunodeficiency virus (HIV) or human T-lymphotropic virus (HTLV) Zynteglo has not been studied in patients with HIV-1, HIV-2, HTLV-1, or HTLV-2. A negative serology test for HIV is necessary to ensure acceptance of apheresis material for Zynteglo manufacturing.
Apheresis material from patients with a positive test for HIV will not be accepted for Zynteglo manufacturing. 6 for full details on the administration process). After completion of the 4-day course of myeloablative conditioning, there must be a minimum of 48 hours of washout before Zynteglo infusion.
Before infusion, it must be confirmed that the patient’s identity matches the unique patient information on the Zynteglo infusion bag(s). 4). Zynteglo infusion should be completed as soon as possible and no more than 4 hours after thawing.
Each infusion bag should be administered in less than 30 minutes. In the event that more than one infusion bag is provided, all infusion bags must be administered. The entire volume of each infusion bag should be infused. Standard procedures for patient management after HSC transplantation should be followed after Zynteglo infusion.
If myelodysplasia, leukaemia, or lymphoma is detected in any patient who received Zynteglo, blood samples should be collected for integration site analysis. 2). Interference with serology testing It is important to note that patients who have received Zynteglo are likely to test positive by polymerase chain reaction (PCR) assays for HIV due to LVV provirus insertion, resulting in a false positive test for HIV.
Therefore, patients who have received Zynteglo should not be screened for HIV infection using a PCR-based assay. Medicinal product no longer authorised6 Engraftment failure as measured by neutrophil engraftment Treatment with Zynteglo involves the infusion and engraftment of CD34+ HSCs that have been genetically modified ex vivo with a LVV.
In clinical trials, no patients failed to engraft bone marrow, as measured by neutrophil engraftment (N=45). 0 (13, 38) after medicinal product infusion. Failure of neutrophil engraftment is a short-term but potentially severe risk, defined as failure to achieve 3 consecutive absolute neutrophil counts (ANC) ≥500 cells/μL obtained on different days by Day 43 after infusion of Zynteglo.
2). Delayed platelet engraftment Platelet engraftment is defined as 3 consecutive platelet values ≥20 × 109/L obtained on different days after Zynteglo infusion, with no platelet transfusions administered for 7 days immediately preceding and during the evaluation period.
0 (19, 191) in clinical trials (N=45). No correlation was observed between incidence of bleeding and delayed platelet engraftment. Patients should be made aware of the risk of bleeding until platelet recovery has been achieved. Patients should be monitored for thrombocytopenia and bleeding according to standard guidelines.
Platelet counts should be monitored according to medical judgment until platelet engraftment and platelet recovery are achieved. Blood cell count determination and other appropriate testing should be promptly considered whenever clinical symptoms suggestive of bleeding arise.
5). If a patient requires anti-retrovirals for HIV prophylaxis, Zynteglo treatment, including mobilisation and apheresis of CD34+ cells through Zynteglo infusion, should be delayed until an HIV infection could be adequately ruled out according to local guidance for HIV testing.
Sodium content This medicinal product contains 391-1564 mg sodium per dose equivalent to 20 to 78% of the WHO recommended maximum daily intake of 2 g sodium for an adult.