Zynteglo betibeglogene autotemcel 20000000 1/1 Suspension, 1 suspension
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Other hematological agents class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Betibeglogene autotemcel injection is used to treat anemia (a lower than normal number of red blood cells) in people who require regular blood transfusions to treat beta thalassemia (Cooley's anemia; an inherited condition that causes a low number of red blood cells). Betibeglogene autotemcel injection is in a class of medications called autologous gene therapy, a type of medication prepared using cells from the patient's own blood stem cells. It works by helping your body to produce enough red blood cells so that regular blood transfusions are not necessary.
Read the full MedlinePlus article ↗- Yes — Zynteglo is designed as a one-time treatment. It permanently modifies your own stem cells so they produce working hemoglobin going forward. That said, the full process takes...
- There's quite a bit of preparation involved. First, you'll receive medications to push stem cells out of your bone marrow into your bloodstream, then they're collected through a pr...
- What happens to my body before I actually get the infusion?
- The most common side effects — many of which are actually related to the chemotherapy conditioning rather than the infusion itself — include mouth sores, fever, low white blood cel...
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🧪 Inactive Ingredients / Excipients
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UNII 2UT2KB9SRE
Cryopreservation solution containing DMSO and other cryoprotectants. It protects cells and tissues during freezing and storage by preventing ice crystal formation that could damage cell structures.
1 inactive ingredient listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
| Medicare Part B allowsASP · J3393 | No ASP payment limit on file for J3393 this quarter. | |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Zynteglo 20000000 1this 73554-3111-01 | Genetix | 1 suspension | — | — | FDA listed | — |
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⏳ Availability & biosimilar status
Biologics have no small-molecule generics; biosimilar competition is tracked in the FDA Purple Book.
Why the date isn’t exact: Biosimilar timing can change because patents may be challenged, settled, licensed, added or removed, and litigation can move the real date earlier or later.
🛈 What do these terms mean?
- Biologic patent
- A patent the reference product’s maker has publicly listed. A biosimilar generally can’t launch until these expire — unless they’re invalidated or resolved in a settlement.
- Reference-product exclusivity
- A flat 12 years of FDA market protection from the biologic’s first licensure (the BPCIA). No biosimilar can be licensed before it ends, regardless of patents.
- Interchangeable exclusivity
- The first interchangeable biosimilar can earn a period as the only interchangeable version (pharmacists can substitute it without the prescriber).
- Earliest biosimilar (LOE)
- The latest of all the dates above — the soonest a biosimilar can realistically reach the market. Litigation and settlements can move it earlier.
Biologics have no small-molecule “generics” — competition comes from FDA-licensed biosimilars, tracked in the FDA Purple Book.
| Code | What it grants | Expires |
|---|---|---|
| RefProduct | Reference-product exclusivity (12-year, BPCIA) — no biosimilar can be licensed before this date | Aug 17, 2034 |
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 73554-3111-01 You're viewing this | 1 SUSPENSION in 1 BAG (73554-3111-1) | 2022-08-17 | Active |
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| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | ✓ Available |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full FDA label FDA SPL
🎯 Indications and Usage ▾
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 )
⏱️ Dosage and Administration ▾
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 )
2.1Dose 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.
2.2Preparation 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 co…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS ZYNTEGLO is a cell suspension for intravenous infusion. ZYNTEGLO is composed of up to four infusion bags which contain 2.0 to 20 × 10 6 cells/mL suspended in cryopreservation solution [see How Supplied/Storage and Handling (16) ] . Each infusion bag contains approximately 20 mL of ZYNTEGLO.
A single dose of ZYNTEGLO contains a minimum of 5.0 × 10 6 CD34+ cells per kg of body weight, suspended in cryopreservation solution . See the Lot Information Sheet for actual dose. ZYNTEGLO is a cell suspension for intravenous infusion.
( 3 ) A single dose of ZYNTEGLO contains a minimum of 5.0 × 10 6 CD34+ cells/kg of body weight, in one or more infusion bags. ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS None. None. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS 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 )
5.1Delayed 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.
5.2Risk of Neutrophil Engraftment Failure There is a potential risk of neutrophil engraftment failure after treatment with ZYNTEGLO. Neutrophil engraftment failure is defined as failure to achieve three consecutive absolute neutrophil counts (ANC) ≥ 500 cells/microliter obtained on different days by Day 43 after infusion of ZYNTEGLO. Monitor neutrophil counts until engraftment has been achieved.
If neutrophil engraftment failure occurs in a patient treated with ZYNTEGLO, provide rescue treatment with the back-up collection of CD34+ cells.
5.3Risk of Insertional Oncogenesis There is a potential risk of lentiviral vector (LVV)-mediated insertional oncogenesis after treatment with ZYNTEGLO. Patients treated with ZYNTEGLO may develop hematologic malignancies and should be monitored lifelong. Monitor for hematologic malignancies with a complete blood count (with differential) at Month 6 and Month 12 and then at least annually for at least 15 years after treatment with ZYNTEGLO, and integration site analysis at Months 6, 12, and as warranted.
In the event that a malignancy occurs, contact Genetix Biotherapeutics at 1-833-999-6378 for reporting and to obtain instructions on collection of samples for testing.
5.4Hypersensitivity Reactions Allergic reactions may occur with the infusion of ZYNTEGLO. The dimethyl sulfoxide (DMSO) in ZYNTEGLO may cause hypersensitivity reactions, including anaphylaxis.
5.5Anti-retroviral and Hydroxyurea Use Patients should not take prophylactic HIV anti-retroviral medications or hydroxyurea for at least one month prior to mobilization, or for the expected duration for elimination of the medications, and until all cycles of apheresis are completed [see Drug Interactions (7.2) ] . If a patient requires anti-retrovirals for HIV prophylaxis, then confirm a negative test for HIV before beginning mobilization and apheresis of CD34+ cells.
5.6Interference with Serology Testing Patients who have received ZYNTEGLO are likely to test positive by polymerase chain reaction (PCR) assays for HIV due to integrated BB305 LVV proviral DNA, 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.
🤒 Adverse Reactions ▾
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.
6.1Clinical 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, phary…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS No formal drug interaction studies have been performed. ZYNTEGLO is not expected to interact with the hepatic cytochrome P-450 family of enzymes or drug transporters. Anti-retrovirals and Hydroxyurea : Do not take anti-retroviral medications or hydroxyurea for one month prior to mobilization, or for the expected duration for elimination of the medications, and until all cycles of apheresis are completed ( 7.2 ) Iron Chelation: Discontinue iron chelators 7 days prior to initiation of myeloablative conditioning.
Avoid use of myelosuppressive iron chelators for 6 months after ZYNTEGLO infusion. ( 7.3 )
7.1Live Vaccines Follow institutional guidelines for vaccine administration. The safety of immunization with live viral vaccines during or following ZYNTEGLO treatment has not been studied.
7.2Anti-retrovirals and Hydroxyurea Patients should not take anti-retroviral medications or hydroxyurea for at least one month prior to mobilization or the expected duration for elimination of the medications, and until all cycles of apheresis are completed [see Warnings and Precautions (5.5) ] . Anti-retroviral medications may interfere with manufacturing of the apheresed cells.
7.3Iron Chelation Drug-drug interactions between iron chelators and the myeloablative conditioning agent must be considered. Iron chelators should be discontinued at least 7 days prior to initiation of conditioning. The prescribing information for the iron chelator(s) and the myeloablative conditioning agent should be consulted for the recommendations regarding co-administration with CYP3A substrates.
Some iron chelators are myelosuppressive. After ZYNTEGLO infusion, avoid use of these iron chelators for 6 months. If iron chelation is needed, consider administration of non-myelosuppressive iron chelators .
Phlebotomy can be used in lieu of iron chelation, when appropriate [see Clinical Studies (14) ] .
7.4Erythropoiesis-Stimulating Agents There is no clinical experience with the use of erythropoiesis-stimulating agents in patients treated with ZYNTEGLO.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy 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.
8.2Lactation 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. Therefore, ZYNTEGLO is not recommended for women who are breastfeeding, and breastfeeding after ZYNTEGLO infusion should be discussed with the treating physician.
8.3Females and Males of Reproductive Potential Pregnancy Testing A negative serum pregnancy test must be confirmed prior to the start of mobilization and re-confirmed prior to conditioning procedures and before ZYNTEGLO administration. Contraception There are insufficient exposure data to provide a precise recommendation on duration of contraception following treatment with ZYNTEGLO. Women of childbearing potential and men capable of fathering a child should use an effective method of contraception (intra-uterine device or combination of hormonal and barrier contraception) from start of mobilization through at least 6 months after administration of ZYNTEGLO.
Advise patients of the risks associated with conditioning agents. Infertility There are no data on the effects of ZYNTEGLO on fertility. Data are available on the risk of infertility with myeloablative conditioning.
Advise patients of the option to cryopreserve semen or ova before treatment, if appropriate.
8.4Pediatric Use The safety and efficacy of ZYNTEGLO have been established in pediatric patients with β-thalassemia requiring regular transfusions. Use of ZYNTEGLO is supported by two Phase 3 studies [see Clinical Studies (14) ] that included 27 pediatric patients in the following age groups: 16 children (less than 12 years) and 11 adolescents (age 12 years to less than 18 years). No differences in efficacy or clinical safety were observed between the adult and pediatric subgroups.
Engraftment times were longer in pediatric patients, but not associated with increases in infections or bleeding events. The median (min, max) time to neutrophil engraftment for patients less than 18 years was 26 (16, 39) days versus 21 (13, 27) days for patients 18 years or older. The median (min, max) time to platelet engraftment for patients less than 18 years was 50 (20, 94) days versus 43 (21, 58) days for patients 18 years or older.
Longer engraftment time was associated with intact spleens. The safety and efficacy of ZYNTEGLO in children less than 4 years of age have not been established. No data are available.
8.5Geriatric Use ZYNTEGLO has not been studied in patients > 65 years of age. Hematopoietic stem cell (HSC) transplantation must be appropriate for a patient to be treated with ZYNTEGLO.
8.6Patients Seropositive for Human Immunodeficiency Virus (HIV) 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 fr…
🤰 Pregnancy ▾
8.1Pregnancy 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.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and efficacy of ZYNTEGLO have been established in pediatric patients with β-thalassemia requiring regular transfusions. Use of ZYNTEGLO is supported by two Phase 3 studies [see Clinical Studies (14) ] that included 27 pediatric patients in the following age groups: 16 children (less than 12 years) and 11 adolescents (age 12 years to less than 18 years). No differences in efficacy or clinical safety were observed between the adult and pediatric subgroups.
Engraftment times were longer in pediatric patients, but not associated with increases in infections or bleeding events. The median (min, max) time to neutrophil engraftment for patients less than 18 years was 26 (16, 39) days versus 21 (13, 27) days for patients 18 years or older. The median (min, max) time to platelet engraftment for patients less than 18 years was 50 (20, 94) days versus 43 (21, 58) days for patients 18 years or older.
Longer engraftment time was associated with intact spleens. The safety and efficacy of ZYNTEGLO in children less than 4 years of age have not been established. No data are available.
🧓 Geriatric Use ▾
8.5Geriatric Use ZYNTEGLO has not been studied in patients > 65 years of age. Hematopoietic stem cell (HSC) transplantation must be appropriate for a patient to be treated with ZYNTEGLO.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action 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 ). β A-T87Q -globin can be quantified relative to other globin species in peripheral blood using high-performance liquid chromatography. β A-T87Q -globin expression is designed to correct the β/α-globin imbalance in erythroid cells of patients with β-thalassemia and has the potential to increase functional adult HbA and total Hb to normal levels and eliminate dependence on regular pRBC transfusions.
12.2Pharmacodynamics HbA T87Q generally increased steadily after ZYNTEGLO infusion and stabilized by approximately Month 6 after infusion (Figure 1). Patients had a Month 6 median (min, max) HbA T87Q of 8.7 (0.0, 12.0) g/dL in the ongoing Phase 3 studies, Study 1 and Study 2 (N = 35). HbA T87Q remained durable with a median (min, max) of 8.8 (0.3, 12.4) g/dL at Month 24 in the ongoing Phase 3 studies (N = 30).
HbA T87Q in the Phase 3 studies continued to remain durable at last follow-up through Month 36, demonstrating sustained expression of the β A-T87Q protein derived from irreversible integration of the β A-T87Q -globin gene into long-term hematopoietic stem cells (HSCs). Figure 1: Median of HbA T87Q Over Time Bars represent interquartile ranges , Only one patient in Study 1 had HbA T87Q data at Month 48; this patient did not achieve TI, which accounts for the drop in median HbA T87Q for Study 1 at Month 48 Figure 1
12.3Pharmacokinetics 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.
🧬 Mechanism of Action ▾
12.1Mechanism of Action 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 ). β A-T87Q -globin can be quantified relative to other globin species in peripheral blood using high-performance liquid chromatography. β A-T87Q -globin expression is designed to correct the β/α-globin imbalance in erythroid cells of patients with β-thalassemia and has the potential to increase functional adult HbA and total Hb to normal levels and eliminate dependence on regular pRBC transfusions.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING ZYNTEGLO is supplied in up to four infusion bags containing a frozen suspension of genetically modified autologous cells, enriched for CD34+ cells. Each bag contains approximately 20 mL. Each infusion bag is individually packed within an overwrap in a metal cassette.
ZYNTEGLO is shipped from the manufacturing facility to the treatment center storage facility in a cryoshipper, which may contain multiple metal cassettes intended for a single patient. A Lot Information Sheet is affixed inside the shipper. 20 mL infusion bag, overwrap, and metal cassette (NDC 73554-3111-1) Match the identity of the patient with the patient identifiers on the metal cassette(s), infusion bag(s), and Lot Information Sheet upon receipt.
Keep the infusion bag(s) in the metal cassette(s) and store in the vapor phase of liquid nitrogen at less than or equal to -140°C (≤ -220°F) until ready for thaw and administration. Thaw ZYNTEGLO prior to infusion [see Dosage and Administration (2.2) ]. Do not re-freeze after thawing.
Do not irradiate ZYNTEGLO, as this could lead to inactivation.
📦 Storage and Handling ▾
Match the identity of the patient with the patient identifiers on the metal cassette(s), infusion bag(s), and Lot Information Sheet upon receipt. Keep the infusion bag(s) in the metal cassette(s) and store in the vapor phase of liquid nitrogen at less than or equal to -140°C (≤ -220°F) until ready for thaw and administration. Thaw ZYNTEGLO prior to infusion [see Dosage and Administration (2.2) ].
Do not re-freeze after thawing. Do not irradiate ZYNTEGLO, as this could lead to inactivation.
📋 Description ▾
11 DESCRIPTION ZYNTEGLO (betibeglogene autotemcel) is a β A-T87Q -globin gene therapy consisting of autologous CD34+ cells, containing hematopoietic stem cells (HSCs), transduced with BB305 LVV encoding β A-T87Q -globin, suspended in cryopreservation solution. ZYNTEGLO is intended for one-time administration to add functional copies of a modified form of the β-globin gene (β A-T87Q -globin gene) into the patient's own HSCs. ZYNTEGLO is prepared from the patient's own HSCs, which are collected via apheresis procedure(s).
The autologous cells are enriched for CD34+ cells, then transduced ex vivo with BB305 LVV, a self-inactivating LVV. The promoter, a regulatory element of the LVV that controls the expression of the transgene selected for BB305 LVV, is a cellular (non-viral) promoter that controls gene expression specific to the erythroid lineage cells (red blood cells and their precursors). BB305 LVV encodes β A-T87Q -globin.
The transduced CD34+ cells are washed, formulated into a suspension, and then cryopreserved. ZYNTEGLO is frozen in a patient-specific infusion bag(s) and is thawed prior to administration [see Dosage and Administration (2.2) , How Supplied/Storage and Handling (16) ] . The thawed product is colorless to white to red, including shades of white or pink, light yellow, and orange, and may contain small proteinaceous particles.
Due to the presence of cells, the solution may be clear to slightly cloudy and may contain visible cell aggregates. The formulation contains 5% dimethyl sulfoxide (DMSO).
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Ensure that patients understand the risk of manufacturing failure. In case of manufacturing failure or the need for additional cells, additional cell collection and manufacturing of ZYNTEGLO would be needed [see Dosage and Administration (2.2) ] .
Prior to treatment, advise patients of the following: Risks associated with mobilization and myeloablative conditioning agents [see Dosage and Administration (2.2) , Use in Specific Populations (8.1 , 8.3) ] . Delayed platelet engraftment – A risk of bleeding exists after myeloablative conditioning and before platelet engraftment and may continue after engraftment in patients who have continued thrombocytopenia [see Warnings and Precautions (5.1) ] . Risk of neutrophil engraftment failure –Patients who experience neutrophil engraftment failure will receive rescue treatment with their back-up collection of CD34+ cells [see Warnings and Precautions (5.2) ] .
Risk of insertional oncogenesis – There is a potential risk of insertional oncogenesis after treatment with ZYNTEGLO. Patients should be monitored lifelong. Monitoring will include assessment for hematologic malignancies with a complete blood count at Month 6 and Month 12 and then at least annually for at least 15 years after treatment with ZYNTEGLO.
This will include integration site analysis at Months 6, 12, and as warranted [see Warnings and Precautions (5.3) ] . Advise patients to seek immediate attention for the following: New or worsening bleeding or bruising. Platelet recovery following ZYNTEGLO infusion could be delayed, potentially resulting in an increased risk of bruising or bleeding until platelet recovery has been achieved [see Warnings and Precautions (5.1) , Adverse Reactions (6.1) ] .
Advise patients to: Monitor for signs and symptoms of bleeding and have frequent blood draws for platelet counts, until platelet recovery has been achieved [see Warnings and Precautions (5.1) ] . Have their treating physician contact Genetix Biotherapeutics at 1-833-999-6378 if they are diagnosed with a malignancy [see Warnings and Precautions (5.3) ] . Advise patients that they should not donate blood, organs, tissues, or cells at any time in the future [see Dosage and Administration (2.3) ] .
Advise patients that they may test positive for HIV if tested using a PCR assay after being treated with ZYNTEGLO [see Warnings and Precautions (5.6) ] .