Lovotibeglogene Autotemcel

LYFGENIA adds functional copies of a modified β A -globin gene (threonine [T] replaced with glutamine [Q] at position 87, T87Q or β A-T87Q -globin) into patients' hematopoietic stem cells (HSCs) through transduction of autologous CD34+ cells with BB305 LVV. After LYFGENIA infusion, the transduced CD34+ HSCs engraft in the bone marrow and differentiate to produce red blood cells containing biologically active β A-T87Q -globin that will combine with α-globin to produce functional Hb containing β A-T87Q -globin (HbA T87Q ).

• LYFGENIA is indicated for the treatment of patients 12 years of age or older with sickle cell disease and a history of vaso-occlusive events. LYFGENIA is an autologous hematopoietic stem cell-based gene therapy indicated for the treatment of patients 12 years of age or older with sickle cell disease and a history of vaso-occlusive events.

• 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 LYFGENIA manufacturing. ( 2.2 ) Dosing of LYFGENIA 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 3 × 10 6 CD34+ cells/kg. ( 2.1 ) Myeloablative conditioning must be administered before infusion of LYFGENIA. ( 2.2 ) Following myeloablative conditioning, allow a minimum of 48 hours of washout before LYFGENIA infusion. ( 2.2 ) Verify that the patient's identity matches the unique patient identification information on the LYFGENIA infusion bag(s) prior to infusion. ( 2.2 ) Do not sample, alter, irradiate, or refreeze LYFGENIA. ( 2.2 ) Do not use an in-line blood filter or an infusion pump. ( 2.3 ) Administer LYFGENIA within 4 hours after thawing. ( 2.3 ) Administer each infusion bag of LYFGENIA via intravenous infusion over a period of less than 30 minutes. ( 2.3 ) 2.1 Dose LYFGENIA is provided as a single dose for infusion containing a suspension of CD34+ cells in one to four infusion bags. The minimum recommended dose of LYFGENIA is 3 × 10 6 CD34+ cells/kg. See the Lot Information Sheet provided with the product shipment for additional information pertaining to dose.

Delayed Platelet Engraftment : Monitor patients frequently for thrombocytopenia and bleeding until platelet engraftment and platelet recovery are achieved. ( 5.2 ) Neutrophil Engraftment Failure: Monitor absolute neutrophil counts (ANC) after LYFGENIA infusion. If neutrophil engraftment does not occur, administer rescue cells. ( 5.3 ) Insertional Oncogenesis : There is a potential risk of insertional oncogenesis after treatment with LYFGENIA. ( 5.4 ) Hypersensitivity Reactions: Monitor for hypersensitivity reactions during infusion. ( 5.5 ) 5.1 Hematologic Malignancy Hematologic malignancy has occurred in patients treated with LYFGENIA (Study 1, Group A). At the time of initial product approval, two patients treated with an earlier version of LYFGENIA using a different manufacturing process and transplant procedure (Study 1, Group A) developed acute myeloid leukemia (AML). One patient with α-thalassemia trait (Study 1, Group C) has been diagnosed with myelodysplastic syndrome (MDS) [see Adverse Reactions (6.1) ] . The additional hematopoietic stress associated with mobilization, conditioning, and infusion of LYFGENIA, including the need to regenerate the hematopoietic system, may increase the risk of a hematologic malignancy. Patients with sickle cell disease have an increased risk of hematologic malignancy as compared to the general population. 3, 4 Patients treated with LYFGENIA may develop hematologic malignancies and should have lifelong monitoring.

The following adverse reactions are described elsewhere in the labeling: Hematologic Malignancy [see Warnings and Precautions (5.1) ] Delayed Platelet Engraftment [see Warnings and Precautions (5.2) ] Neutrophil Engraftment Failure [see Warnings and Precautions (5.3) ] Insertional Oncogenesis [see Warnings and Precautions (5.4) ] Hypersensitivity Reactions [see Warnings and Precautions (5.5) ] Most common adverse reactions ≥ Grade 3 (incidence ≥ 20%) were stomatitis, thrombocytopenia, neutropenia, febrile neutropenia, anemia, and leukopenia. ( 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. Safety was based on patients with sickle cell disease in one open-label, single-arm clinical trial and one long-term follow-up study. Of the 54 patients who initiated stem cell collection, the median (min, max) age across the studies was 25 (12, 43) years, 63% were males, 89% were Black or African American, 2% were Asian, 2% White/Caucasian and 4% were not reported. The median (min, max) duration of follow-up was 42 (12, 87) months. Mobilization and apheresis triggered SAEs of sickle cell crisis in 6 (14%, 6/44) patients who initiated mobilization in the intent-to-treat population.

8.1 Pregnancy Risk Summary There are no available data on LYFGENIA 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 LYFGENIA to assess whether it can cause fetal harm when administered to a pregnant woman. It is not known whether LYFGENIA has the potential to be transferred to the fetus. Therefore, LYFGENIA should not be administered to women who are pregnant, and pregnancy after LYFGENIA infusion should be discussed with the treating physician. 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 LYFGENIA 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 LYFGENIA and any potential adverse effects on the breastfed child from LYFGENIA. Therefore, LYFGENIA is not recommended for women who are breastfeeding, and breastfeeding after LYFGENIA infusion should be discussed with the treating physician.

Metabolism

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

1. 1Alopecia526%
2. 2Mucosal Inflammation526%
3. 3Pain421%
4. 4Nausea316%
5. 5Stomatitis316%
6. 6Ageusia211%
7. 7Oral Pain211%
8. 8Pruritus211%
9. 9Vomiting211%
10. 10Anxiety15.3%
11. 11Autoimmune Haemolytic Anaemia15.3%
12. 12Blood Pressure Decreased15.3%
13. 13Chapped Lips15.3%
14. 14Decreased Appetite15.3%
15. 15Dizziness15.3%

The 2 most recently updated of 2 ClinicalTrials.gov registrations naming Lovotibeglogene Autotemcel as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Study Evaluating the Safety and Efficacy of Lovo-cel in Severe Sickle Cell Disease
  Completed · Phase 1 · Phase 2 · Interventional · 54 enrolled · Genetix Biotherapeutics Inc.
  NCT02140554updated 2025-03-14
• A Study Evaluating Gene Therapy With BB305 Lentiviral Vector in Sickle Cell Disease
  Active not recruiting · Phase 3 · Interventional · 35 enrolled · Genetix Biotherapeutics Inc.
  NCT04293185updated 2024-12-10

Frequently asked questions

How does Lovotibeglogene Autotemcel work?

LYFGENIA adds functional copies of a modified β A -globin gene (threonine [T] replaced with glutamine [Q] at position 87, T87Q or β A-T87Q -globin) into patients' hematopoietic stem cells (HSCs) through transduction of autologous CD34+ cells with BB305 LVV. After LYFGENIA infusion, the transduced CD34+ HSCs engraft in the bone marrow and differentiate to produce red blood cells containing biologically active β A-T87Q -globin that will combine with α-globin to produce functional Hb containing β A-T87Q -globin (HbA T87Q ).

What is Lovotibeglogene Autotemcel used for?

According to FDA labeling, Lovotibeglogene Autotemcel carries indications including: LYFGENIA is indicated for the treatment of patients 12 years of age or older with sickle cell disease and a history of vaso-occlusive events. LYFGENIA is an autologous hematopoietic stem cell-based gene therapy indicated for the treatment of patients 12 years of age or older with sickle cell disease and a history of vaso-occlusive events.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Lovotibeglogene Autotemcel?

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

What are the brand names for Lovotibeglogene Autotemcel?

Lovotibeglogene Autotemcel is marketed under brand names including Lyfgenia.

What are the contraindications for Lovotibeglogene Autotemcel?

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