Identification
- Summary
Lovotibeglogene autotemcel is an autologous CD34+ cell therapy used to treat sickle cell disease by providing a functional copy of the beta-globin gene
- Brand Names
- Lyfgenia
- Generic Name
- Lovotibeglogene autotemcel
- DrugBank Accession Number
- DB18680
- Background
Lovotibeglogene autotemcel consists of autologous hematopoietic stem and progenitor cells transduced with the BB305 lentiviral vector encoding a modified β-globin gene. Specifically, lovotibeglogene autotemcel provides a functional copy of a modified beta-globin gene (βA-T87Q-globin) that when combined with α-globin, produces hemoglobins with similar oxygen-binding capacity as wild type hemoglobin. Additionally, the T87Q mutation also inhibits HbS polymerization, thus limiting sickling of red blood cells.1,2
On December 8, 2023, lovotibeglogene autotemcel was approved by the FDA under the brand name Lyfgenia for the treatment of sickle cell disease (SCD) in patients ages 12 and older who have a history of vaso-occlusive events.3 It was approved alongside exagamglogene autotemcel (Casgevy), another gene therapy, with the two treatments comprising the first cell-based gene therapies for the treatment of SCD in patients 12 years and older to be approved by the FDA.4
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Gene Therapies
Other gene therapies - Synonyms
- Lovo-cel
- External IDs
- bb1111
Pharmacology
- Indication
Lovotibeglogene autotemcel is indicated for the treatment of patients 12 years of age or older with sickle cell disease and a history of vaso-occlusive events.2
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Sickle cell disease (scd) •••••••••••• ••••••• •• •••••••••••••• •••••• •••••••••• - Contraindications & Blackbox Warnings
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After lovotibeglogene autotemcel infusion, the transduced CD34+ HSCs engraft in the bone marrow and differentiate to produce red blood cells containing biologically active βA-T87Q-globin that will combine with α-globin to produce functional Hb containing βA-T87Q-globin (HbAT87Q). βA-T87Q-globin can be distinguished from wildtype βA-globin and from βS-globin through reverse-phase high-performance liquid chromatography (RPHPLC) or ultra-high performance liquid chromatography (UPLC). HbAT87Q has similar oxygen-binding affinity and oxygen hemoglobin dissociation curve to wild type HbA, reduces intracellular and total hemoglobin S (HbS) levels, and is designed to sterically inhibit polymerization of HbS thereby limiting the sickling of red blood cells.2
HbAT87Q generally increased steadily after lovotibeglogene autotemcel infusion and stabilized by approximately Month 6 after infusion. Patients had a Month 6 median (min, max) HbAT87Q of 5.2 (2.6, 8.8) g/dL in an ongoing Phase 1/2 Study Group C (Study 1-C) (N = 33). HbAT87Q remained durable with a median (min, max) of 5.5 (2.4, 9.4) g/dL at Month 24 (N = 34). HbAT87Q comprised a median (min, max) 45.7 (26.9, 63.2) (N = 34) percent of total non-transfused Hb at Month 24.2
Expression of HbAT87Q continued to remain durable through Month 48 (N = 10), demonstrating sustained expression of the βA-T87Q protein derived from irreversible integration of the βA-T87Q-globin gene into long-term hematopoietic stem cells (HSCs).2
- Mechanism of action
Lovotibeglogene autotemcel adds functional copies of a modified βA-globin gene (threonine [T] replaced with glutamine Q at position 87, T87Q or βA-T87Q-globin) into patients’ hematopoietic stem cells (HSCs) through transduction of autologous CD34+ cells with BB305 LVV.2
Target Actions Organism AHemoglobin subunit beta gene replacementHumans - Absorption
Lovotibeglogene autotemcel is an autologous gene therapy that 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.2
- Volume of distribution
Lovotibeglogene autotemcel is an autologous gene therapy that 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.2
- Protein binding
Lovotibeglogene autotemcel is an autologous gene therapy that 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.2
- Metabolism
Lovotibeglogene autotemcel is an autologous gene therapy that 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.2
- Route of elimination
Lovotibeglogene autotemcel is an autologous gene therapy that 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.2
- Half-life
Lovotibeglogene autotemcel is an autologous gene therapy that 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.2
- Clearance
Lovotibeglogene autotemcel is an autologous gene therapy that 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.2
- Adverse Effects
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There are no available data on lovotibeglogene autotemcel administration in pregnant women. Consider the risks associated with myeloablative conditioning agents on pregnancy and fertility.2
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, lovotibeglogene autotemcel should not be administered to women who are pregnant, and pregnancy after lovotibeglogene autotemcel infusion should be discussed with the treating physician.2
No carcinogenicity studies have been performed with lovotibeglogene autotemcel.2
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- No interactions found.
Products
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Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Lyfgenia Suspension 20000000 1/20mL Intravenous bluebird bio, Inc. 2023-12-08 Not applicable US 
Categories
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Humans
Chemical Identifiers
- UNII
- 2C6A9NH2Z8
- CAS number
- Not Available
References
- General References
- Kanter J, Thompson AA, Pierciey FJ Jr, Hsieh M, Uchida N, Leboulch P, Schmidt M, Bonner M, Guo R, Miller A, Ribeil JA, Davidson D, Asmal M, Walters MC, Tisdale JF: Lovo-cel gene therapy for sickle cell disease: Treatment process evolution and outcomes in the initial groups of the HGB-206 study. Am J Hematol. 2023 Jan;98(1):11-22. doi: 10.1002/ajh.26741. Epub 2022 Oct 10. [Article]
- FDA Approved Drug Products: LYFGENIA® (lovotibeglogene autotemcel) suspension for intravenous infusion [Link]
- bluebird bio Announces FDA Approval of LYFGENIA™ (lovotibeglogene autotemcel) for Patients Ages 12 and Older with Sickle Cell Disease and a History of Vaso-Occlusive Events [Link]
- FDA Press Announcements: FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease [Link]
- External Links
- 2671958
- Wikipedia
- Lovotibeglogene_autotemcel
Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Suspension Intravenous 20000000 1/20mL - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Targets
References
- FDA Approved Drug Products: LYFGENIA® (lovotibeglogene autotemcel) suspension for intravenous infusion [Link]
Drug created at October 17, 2023 16:23 / Updated at February 15, 2024 07:14