Lovotibeglogene autotemcel

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. Limitations of Use Following treatment with LYFGENIA, patients with α-thalassemia trait (-α3.7/-α3.7) may experience anemia with erythroid dysplasia that may require chronic red blood cell transfusions. LYFGENIA has not been studied in patients with more than two α-globin gene deletions.

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 ). β A-T87Q -globin can be distinguished from wildtype β A -globin and from β S -globin through reverse-phase high-performance liquid chromatography (RPHPLC) or ultra-high performance liquid chromatography (UPLC).

For autologous use only. For one-time single-dose intravenous 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. Dosing of LYFGENIA is based on the number of CD34+ cells in the infusion bag(s) per kg of body weight. The minimum recommended dose is 3 × 10 6 CD34+ cells/kg. Myeloablative conditioning must be administered before infusion of LYFGENIA. Following myeloablative conditioning, allow a minimum of 48 hours of washout before LYFGENIA infusion. Verify that the patient's identity matches the unique patient identification information on the LYFGENIA infusion bag(s) prior to infusion. Do not sample, alter, irradiate, or refreeze LYFGENIA. Do not use an in-line blood filter or an infusion pump. Administer LYFGENIA within 4 hours after thawing.

None. None.

Boxed warning (hematologic malignancy): Hematologic malignancy has occurred in patients treated with LYFGENIA. Monitor patients closely for evidence of malignancy through complete blood counts at least every 6 months and through integration site analysis at Months 6, 12, and as warranted. Delayed Platelet Engraftment: Monitor patients frequently for thrombocytopenia and bleeding until platelet engraftment and platelet recovery are achieved. Neutrophil Engraftment Failure: Monitor absolute neutrophil counts (ANC) after LYFGENIA infusion. If neutrophil engraftment does not occur, administer rescue cells. Insertional Oncogenesis: There is a potential risk of insertional oncogenesis after treatment with LYFGENIA. Hypersensitivity Reactions: Monitor for hypersensitivity reactions during infusion.

The following adverse reactions are described elsewhere in the labeling: Hematologic Malignancy Delayed Platelet Engraftment Neutrophil Engraftment Failure Insertional Oncogenesis Hypersensitivity Reactions Most common adverse reactions ≥ Grade 3 (incidence ≥ 20%) were stomatitis, thrombocytopenia, neutropenia, febrile neutropenia, anemia, and leukopenia.

No formal drug interaction studies have been performed. LYFGENIA is not expected to interact with the hepatic cytochrome P-450 family of enzymes or drug transporters. Anti-retrovirals: Discontinue anti-retroviral medications at least one month prior to mobilization and until all cycles of apheresis are completed. There are some long-acting anti-retroviral medications that may require a longer duration of discontinuation for elimination of the medication. Hydroxyurea: Discontinue 2 months prior to mobilization and 2 days prior to conditioning. Iron chelation: Discontinue at least 7 days prior to mobilization and conditioning.

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. Do not re-freeze after thawing.