{{Short description|Gene therapy}} {{Use American English|date=December 2023}} {{Use dmy dates|date=December 2023}} {{cs1 config |display-authors=6}} {{Infobox drug | image = | width = | alt = | caption =
<!-- Gene therapy data --> | gt_target_gene = | gt_vector = | gt_nucleic_acid_type = | gt_editing_method = | gt_delivery_method =
<!-- Clinical data --> | pronounce = | tradename = Lyfgenia | Drugs.com = {{drugs.com|parent|Lyfgenia}} | MedlinePlus = | DailyMedID = Lovotibeglogene autotemcel | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> | pregnancy_AU_comment = | pregnancy_category = | routes_of_administration = Intravenous | class = | ATC_prefix = B06 | ATC_suffix = AX06 | ATC_supplemental = | biosimilars =
<!-- Legal status --> | legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled --> | legal_AU_comment = | legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F --> | legal_BR_comment = | legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII --> | legal_CA_comment = | legal_DE = <!-- Anlage I, II, III or Unscheduled --> | legal_DE_comment = | legal_NZ = <!-- Class A, B, C --> | legal_NZ_comment = | legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C --> | legal_UK_comment = | legal_US = Rx-only | legal_US_comment = <ref name="Lyfgenia FDA label">{{cite web | title=Lyfgenia- lovotibeglogene autotemcel suspension | website=DailyMed | date=22 December 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0d1b475e-5781-2bd1-e063-6294a90a7311 | access-date=30 December 2023}}</ref><ref name="FDA Lyfgenia">{{cite web | title=Lyfgenia | website=U.S. Food and Drug Administration (FDA) | date=8 December 2023 | url=https://www.fda.gov/vaccines-blood-biologics/lyfgenia | access-date=9 December 2023 | archive-date=8 December 2023 | archive-url=https://web.archive.org/web/20231208210239/https://www.fda.gov/vaccines-blood-biologics/lyfgenia | url-status=live }} {{PD-notice}}</ref> | legal_EU = | legal_EU_comment = | legal_UN = <!-- N I, II, III, IV / P I, II, III, IV --> | legal_UN_comment = | legal_status = <!-- For countries not listed above -->
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<!-- Identifiers --> | CAS_number = | CAS_supplemental = | PubChem = | IUPHAR_ligand = | DrugBank = DB18680 | ChemSpiderID = | UNII = 2C6A9NH2Z8 | KEGG = D12765 | ChEBI = | ChEMBL = | NIAID_ChemDB = | PDB_ligand = | synonyms = bb1111, lovo-cel, LentiGlobin for sickle cell disease
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'''Lovotibeglogene autotemcel''', sold under the brand name '''Lyfgenia''', is a lentiviral gene therapy used for the treatment of sickle cell disease.<ref name="Lyfgenia FDA label" /><ref name="FDA PR 20231208" /><ref>{{cite journal |last1=Kanter |first1=Julie |last2=Thompson |first2=Alexis A. |last3=Pierciey |first3=Francis J. |last4=Hsieh |first4=Matthew |last5=Uchida |first5=Naoya |last6=Leboulch |first6=Philippe |last7=Schmidt |first7=Manfred |last8=Bonner |first8=Melissa |last9=Guo |first9=Ruiting |last10=Miller |first10=Alex |last11=Ribeil |first11=Jean-Antoine |last12=Davidson |first12=David |last13=Asmal |first13=Mohammed |last14=Walters |first14=Mark C. |last15=Tisdale |first15=John F. |title=Lovo-cel gene therapy for sickle cell disease: Treatment process evolution and outcomes in the initial groups of the HGB -206 study |journal=American Journal of Hematology |date=January 2023 |volume=98 |issue=1 |pages=11–22 |doi=10.1002/ajh.26741|pmid=36161320 |pmc=10092845 |s2cid=252544370 |doi-access=free }}</ref><ref>{{cite journal |last1=Sheridan |first1=Cormac |title=The world's first CRISPR therapy is approved: who will receive it? |journal=Nature Biotechnology |date=21 November 2023 |volume=42 |issue=1 |pages=3–4 |doi=10.1038/d41587-023-00016-6 |pmid=37989785 |s2cid=265350318 |url=https://www.nature.com/articles/d41587-023-00016-6 |access-date=4 December 2023 |archive-date=4 December 2023 |archive-url=https://web.archive.org/web/20231204182913/https://www.nature.com/articles/d41587-023-00016-6 |url-status=live |url-access=subscription }}</ref>
The most common side effects include stomatitis (mouth sores of the lips, mouth, and throat), low levels of platelets, white blood cells, and red blood cells, and febrile neutropenia (fever and low white blood cell count), consistent with chemotherapy and underlying disease.<ref name="FDA PR 20231208" />
The US Food and Drug Administration (FDA) approved lovotibeglogene autotemcel in December 2023.<ref name="FDA PR 20231208">{{cite web | title=FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease | website=U.S. Food and Drug Administration (FDA) | date=8 December 2023 | url=https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease | access-date=8 December 2023 | archive-date=8 December 2023 | archive-url=https://web.archive.org/web/20231208165916/https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease }} {{PD-notice}}</ref><ref>{{cite press release | title=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 | publisher=Bluebird Bio | via=Business Wire | date=8 December 2023 | url=https://www.businesswire.com/news/home/20231208492260/en/bluebird-bio-Announces-FDA-Approval-of-LYFGENIA%E2%84%A2-lovotibeglogene-autotemcel-for-Patients-Ages-12-and-Older-with-Sickle-Cell-Disease-and-a-History-of-Vaso-Occlusive-Events | access-date=9 December 2023}}</ref>
== Medical uses == Lovotibeglogene autotemcel is indicated for the treatment of people aged twelve years of age and older with sickle cell disease and a history of vaso-occlusive events.<ref name="Lyfgenia FDA label" /><ref name="FDA PR 20231208" />
The recipient's blood stem cells are genetically modified to produce HbA (T87Q), a gene-therapy derived hemoglobin A, which is similar to the normal adult hemoglobin produced in persons not affected by sickle cell disease.<ref name="FDA PR 20231208" /> Red blood cells containing HbA (T87Q) have a lower risk of sickling and occluding blood flow.<ref name="FDA PR 20231208" /> These modified stem cells are then delivered to the recipient.<ref name="FDA PR 20231208" />
The gene therapy is made from the recipient's own blood stem cells, which are modified, and are given back as a one-time, single-dose infusion as part of a hematopoietic (blood) stem cell transplant.<ref name="FDA PR 20231208" /> Prior to treatment, the recipient's own stem cells are collected, and then the recipient must undergo myeloablative conditioning (high-dose chemotherapy), a process that removes cells from the bone marrow so they can be replaced with the modified cells in lovotibeglogene autotemcel.<ref name="FDA PR 20231208" />
== Side effects == The US FDA label contains a black box warning about hematologic malignancy (blood cancer).<ref name="Lyfgenia FDA label" /><ref name="FDA PR 20231208" />
== History == The safety and effectiveness of lovotibeglogene autotemcel is based on the analysis of data from a single-arm, 24-month multicenter study in participants with sickle cell disease and history of Vaso-occlusive episodes (VOEs) between the ages of twelve and fifty years.<ref name="FDA PR 20231208" /> Effectiveness was evaluated based on complete resolution of VOEs (VOE-CR) between six and eighteen months after infusion with lovotibeglogene autotemcel.<ref name="FDA PR 20231208" /> Twenty-eight (88%) of 32 participants achieved VOE-CR during this time period.<ref name="FDA PR 20231208" />
The FDA granted the application for lovotibeglogene autotemcel priority review, orphan drug, fast track, and regenerative medicine advanced therapy designations.<ref name="FDA PR 20231208" /> The FDA granted approval of Lyfgenia to Bluebird Bio Inc.<ref name="FDA PR 20231208" />
In March 2025, Cohen Children's Medical Center announced that through the use of this treatment the first person in New York State was cured of sickle cell anemia.<ref>{{cite web | title=Long Island man is first in New York history to be cured of sickle cell anemia - CBS New York | website=CBS News | date=13 March 2025 | url=https://www.cbsnews.com/newyork/news/sickle-cell-anemia-cure-new-york/ }}</ref>
== Society and culture == === Economics === The cost effectiveness threshold of the therapy is estimated to be between {{US$|1.35 million}} to $2.05 million.<ref>{{cite web |title=ICER Publishes Final Evidence Report on Gene Therapies for Sickle Cell Disease |url=https://icer.org/news-insights/press-releases/icer-publishes-final-evidence-report-on-gene-therapies-for-sickle-cell-disease/ |website=Institute for Clinical and Economic Review |access-date=4 December 2023 |archive-date=4 December 2023 |archive-url=https://web.archive.org/web/20231204221956/https://icer.org/news-insights/press-releases/icer-publishes-final-evidence-report-on-gene-therapies-for-sickle-cell-disease/ |url-status=live }}</ref>
=== Brand names === Lovotibeglogene autotemcel is the international nonproprietary name.<ref>{{cite journal | year = 2022 | title = International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 87 | journal = WHO Drug Information | volume = 36 | issue = 1 | hdl = 10665/352794 | hdl-access = free }}</ref>
Lovotibeglogene autotemcel is sold under the brand name Lyfgenia.<ref name="Lyfgenia FDA label" />
== References == {{reflist}}
== Further reading == * {{cite journal | vauthors = Kanter J, Walters MC, Krishnamurti L, Mapara MY, Kwiatkowski JL, Rifkin-Zenenberg S, Aygun B, Kasow KA, Pierciey FJ, Bonner M, Miller A, Zhang X, Lynch J, Kim D, Ribeil JA, Asmal M, Goyal S, Thompson AA, Tisdale JF | title = Biologic and Clinical Efficacy of LentiGlobin for Sickle Cell Disease | journal = The New England Journal of Medicine | volume = 386 | issue = 7 | pages = 617–628 | date = February 2022 | pmid = 34898139 | doi = 10.1056/NEJMoa2117175 | doi-access = free | title-link = doi }}
== External links == * {{cite web | title=Lovotibeglogene Autotemcel (Code C176855) | website=NCI Thesaurus | url=https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI%20Thesaurus&code=C176855 | archive-url=https://web.archive.org/web/20231210071725/https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI%20Thesaurus&code=C176855 | archive-date=10 December 2023 }}
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{{DEFAULTSORT:Lovotibeglogene Autotemcel}} Category:Approved gene therapies Category:Drugs acting on the blood and blood forming organs Category:Lentiviruses Category:Orphan drugs Category:Sickle-cell disease