exagamglogene autotemcel
{{Short description|Gene therapy}}
{{Use American English|date=December 2023}}
{{Use dmy dates|date=December 2023}}
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| tradename = Casgevy
| Drugs.com = {{drugs.com|monograph|exagamglogene-autotemcel}}
| MedlinePlus = a624018
| DailyMedID = Exagamglogene autotemcel
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| routes_of_administration = Intravenous
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| ATC_prefix = B06
| ATC_suffix = AX05
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| legal_CA = Rx-only
| legal_CA_comment = {{cite web | title=Notice: Multiple additions to the Prescription Drug List (PDL) [2024-12-20] | website=Health Canada | date=20 December 2024 | url=https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/prescription-drug-list/notices-changes/multiple-additions-2024-12-20.html | access-date=21 December 2024}}{{cite web | title=Casgevy product information | website=Health Canada | date=11 October 2024 | url=https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=104074 | access-date=27 December 2024}}
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| legal_UK = POM
| legal_UK_comment = {{cite web | title=Summary of Product Characteristics | url=https://mhraproducts4853.blob.core.windows.net/docs/70a9054b092d2565def369a673ac221b90ebe0fa | format=PDF | publisher=Medicines and Healthcare products Regulatory Agency (MHRA) | date=15 November 2023 | access-date=9 December 2023 | archive-date=8 December 2023 | archive-url=https://web.archive.org/web/20231208212339/https://mhraproducts4853.blob.core.windows.net/docs/70a9054b092d2565def369a673ac221b90ebe0fa | url-status=dead }}{{cite web | title=Casgevy 4–13 x 10Exp6 cells/mL dispersion for infusion | website=Electronic Medicines Compendium | date=24 November 2023 | url=https://www.medicines.org.uk/emc/product/15296/smpc | access-date=9 December 2023 | archive-date=9 December 2023 | archive-url=https://web.archive.org/web/20231209200747/https://www.medicines.org.uk/emc/product/15296/smpc | url-status=live }}
| legal_US = Rx-only
| legal_US_comment = {{cite web | title=Casgevy- exagamglogene autotemcel injection, suspension | website=DailyMed | date=22 January 2024 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7c3e12ad-e2fe-4d3f-a630-ea7364d9e846 | access-date=3 March 2024}}{{cite web | title=Casgevy | website=U.S. Food and Drug Administration (FDA) | date=8 December 2023 | url=https://www.fda.gov/vaccines-blood-biologics/casgevy | access-date=8 December 2023 | archive-date=19 December 2023 | archive-url=https://web.archive.org/web/20231219043210/https://www.fda.gov/vaccines-blood-biologics/casgevy | url-status=live }} {{PD-notice}}
| legal_EU = Rx-only
| legal_EU_comment = {{cite web | title=Casgevy product information | website=Union Register of medicinal products | date=12 February 2024 | url=https://ec.europa.eu/health/documents/community-register/html/h1787.htm | access-date=19 February 2024}}
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| DrugBank = DB15572
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| UNII = S53L777GM8
| KEGG = D12749
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| synonyms = CTX001, exa-cel
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Exagamglogene autotemcel, sold under the brand name Casgevy, is a gene therapy used for the treatment of sickle cell disease and transfusion-dependent beta thalassemia. It was developed by Vertex Pharmaceuticals and CRISPR Therapeutics.{{cite web | vauthors = Stein R | title=FDA advisers see no roadblocks for gene-editing treatment for sickle cell disease | website=NPR | date=31 October 2023 | url=https://www.npr.org/sections/health-shots/2023/10/31/1208041252/a-landmark-gene-editing-treatment-for-sickle-cell-disease-moves-closer-to-realit | access-date=4 December 2023 | archive-date=4 December 2023 | archive-url=https://web.archive.org/web/20231204214937/https://www.npr.org/sections/health-shots/2023/10/31/1208041252/a-landmark-gene-editing-treatment-for-sickle-cell-disease-moves-closer-to-realit | url-status=live }}
The treatment was approved in the United Kingdom for the treatment of sickle cell disease and transfusion-dependent beta thalassemia in November 2023.{{cite press release | title=MHRA authorises world-first gene therapy that aims to cure sickle-cell disease and transfusion-dependent β-thalassemia | website=Medicines and Healthcare products Regulatory Agency (MHRA) | date=16 November 2023 | url=https://www.gov.uk/government/news/mhra-authorises-world-first-gene-therapy-that-aims-to-cure-sickle-cell-disease-and-transfusion-dependent-thalassemia | access-date=8 December 2023 | archive-date=25 November 2023 | archive-url=https://web.archive.org/web/20231125015409/https://www.gov.uk/government/news/mhra-authorises-world-first-gene-therapy-that-aims-to-cure-sickle-cell-disease-and-transfusion-dependent-thalassemia | url-status=live }}{{cite journal | vauthors = Sheridan C | title = The world's first CRISPR therapy is approved: who will receive it? | journal = Nature Biotechnology | date = November 2023 | volume = 42 | issue = 1 | pages = 3–4 | pmid = 37989785 | doi = 10.1038/d41587-023-00016-6 | url = https://www.nature.com/articles/d41587-023-00016-6 | access-date = 4 December 2023 | url-status = live | s2cid = 265350318 | archive-url = https://web.archive.org/web/20231204182913/https://www.nature.com/articles/d41587-023-00016-6 | archive-date = 4 December 2023 | url-access = subscription }}{{cite press release | title=Vertex and CRISPR Therapeutics Announce Authorization of the First CRISPR/Cas9 Gene-Edited Therapy, Casgevy (exagamglogene autotemcel), by the United Kingdom MHRA for the Treatment of Sickle Cell Disease and Transfusion-Dependent Beta Thalassemia | publisher=Vertex Pharmaceuticals | via=Business Wire | date=16 November 2023 | url=https://www.businesswire.com/news/home/20231115290500/en/%C2%A0Vertex-and-CRISPR-Therapeutics-Announce-Authorization-of-the-First-CRISPRCas9-Gene-Edited-Therapy-CASGEVY%E2%84%A2-exagamglogene-autotemcel-by-the-United-Kingdom-MHRA-for-the-Treatment-of-Sickle-Cell-Disease-and-Transfusion-Dependent-Beta-Thalassemia | access-date=9 December 2023 | archive-date=22 November 2023 | archive-url=https://web.archive.org/web/20231122154102/https://www.businesswire.com/news/home/20231115290500/en/%C2%A0Vertex-and-CRISPR-Therapeutics-Announce-Authorization-of-the-First-CRISPRCas9-Gene-Edited-Therapy-CASGEVY%E2%84%A2-exagamglogene-autotemcel-by-the-United-Kingdom-MHRA-for-the-Treatment-of-Sickle-Cell-Disease-and-Transfusion-Dependent-Beta-Thalassemia | url-status=live }} It was approved in the United States for the treatment of sickle cell disease in December 2023 and for the treatment of transfusion-dependent beta thalassemia in January 2024.{{cite press release | title=Vertex and CRISPR Therapeutics Announce US FDA Approval of Casgevy (exagamglogene autotemcel) for the Treatment of Sickle Cell Disease | publisher=Vertex Pharmaceuticals | via=Business Wire | date=8 December 2023 | url=https://www.businesswire.com/news/home/20231208951733/en/Vertex-and-CRISPR-Therapeutics-Announce-US-FDA-Approval-of-CASGEVY%E2%84%A2-exagamglogene-autotemcel-for-the-Treatment-of-Sickle-Cell-Disease | access-date=9 December 2023 | archive-date=9 December 2023 | archive-url=https://web.archive.org/web/20231209193910/https://www.businesswire.com/news/home/20231208951733/en/Vertex-and-CRISPR-Therapeutics-Announce-US-FDA-Approval-of-CASGEVY%E2%84%A2-exagamglogene-autotemcel-for-the-Treatment-of-Sickle-Cell-Disease | url-status=live }}{{Cite web |last=Commissioner |first=Office of the |date=2024-01-16 |title=FDA Roundup: January 16, 2024 |url=https://www.fda.gov/news-events/press-announcements/fda-roundup-january-16-2024 |archive-url=https://web.archive.org/web/20240116233635/https://www.fda.gov/news-events/press-announcements/fda-roundup-january-16-2024 |url-status=dead |archive-date=16 January 2024 |access-date=2024-01-19 |website=FDA |language=en}}
Exagamglogene autotemcel is the first cell-based gene therapy treatment utilizing CRISPR/Cas9 gene editing technology to be approved by the US Food and Drug Administration (FDA).{{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 | url-status=dead }} {{PD-notice}} The most common side effects include low levels of platelets and white blood cells, mouth sores, nausea, musculoskeletal pain, abdominal pain, vomiting, febrile neutropenia (fever and low white blood cell count), headache, and itching.
Medical uses
In the UK, exagamglogene autotemcel is indicated for the treatment of transfusion-dependent beta thalassemia and sickle cell disease in patients aged 12 years and older who should be treated with hematopoietic stem cell transplantation but for whom a suitable stem cell donor is not available.
In the US, exagamglogene autotemcel is indicated for the treatment of sickle cell disease in people aged 12 years and older with recurrent vaso-occlusive crises, and for the treatment of people with transfusion-dependent beta-thalassemia.{{cite press release | title=FDA Roundup: January 16, 2024 | website=U.S. Food and Drug Administration (FDA) | date=16 January 2024 | url=https://www.fda.gov/news-events/press-announcements/fda-roundup-january-16-2024 | access-date=17 January 2024 | archive-date=17 January 2024 | archive-url=https://web.archive.org/web/20240117084736/https://www.fda.gov/news-events/press-announcements/fda-roundup-january-16-2024 | url-status=dead }}
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. 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 exagamglogene autotemcel. The modified blood stem cells are transplanted back into the recipient where they engraft (attach and multiply) within the bone marrow and increase the production of fetal hemoglobin (HbF), a type of hemoglobin that facilitates oxygen delivery.
Side effects
History
The safety and effectiveness of exagamglogene autotemcel were evaluated in an ongoing single-arm, multi-center trial in adult and adolescent participants with sickle cell disease. Participants had a history of at least two protocol-defined severe vaso-occlusive crises during each of the two years prior to screening. The primary efficacy outcome was freedom from severe vaso-occlusive crisis episodes for at least twelve consecutive months during the 24-month follow-up period. A total of 44 participants were treated with exagamglogene autotemcel. Of the 31 participants with sufficient follow-up time to be evaluable, 29 (93.5%) achieved this outcome. All treated participants achieved successful engraftment with no participants experiencing graft failure or graft rejection.
The US Food and Drug Administration (FDA) granted the application for exagamglogene autotemcel priority review, orphan drug, fast track, and regenerative medicine advanced therapy designations. The FDA granted approval of Casgevy to Vertex Pharmaceuticals.
Society and culture
= Legal status =
In December 2023, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a conditional marketing authorization for the medicinal product Casgevy, intended for the treatment of transfusion‑dependent β‑thalassemia and sickle cell disease.{{cite press release | title=First gene editing therapy to treat beta thalassemia and severe sickle cell disease | website=European Medicines Agency (EMA) | date=15 December 2023 | url=https://www.ema.europa.eu/en/news/first-gene-editing-therapy-treat-beta-thalassemia-and-severe-sickle-cell-disease | access-date=16 December 2023 | archive-date=16 December 2023 | archive-url=https://web.archive.org/web/20231216021859/https://www.ema.europa.eu/en/news/first-gene-editing-therapy-treat-beta-thalassemia-and-severe-sickle-cell-disease | url-status=live }} As Casgevy is an advanced therapy medicinal product, the CHMP positive opinion is based on an assessment by the Committee for Advanced Therapies. The applicant for this medicinal product is Vertex Pharmaceuticals (Ireland) Limited.{{cite web | title=Casgevy EPAR | website=European Medicines Agency (EMA) | date=14 December 2023 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/casgevy | access-date=16 December 2023 | archive-date=19 December 2023 | archive-url=https://web.archive.org/web/20231219032405/https://www.ema.europa.eu/en/medicines/human/EPAR/casgevy | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Exagamglogene autotemcel was approved for medical use in the European Union in February 2024.
= Economics =
The therapy has a US list price of {{US$|2.2 million}}.{{Cite web |vauthors=Feuerstein A |date=8 December 2023 |title=In historic decision, FDA approves a CRISPR-based medicine for treatment of sickle cell disease |url=https://www.statnews.com/2023/12/08/fda-approves-casgevy-crispr-based-medicine-for-treatment-of-sickle-cell-disease/ |access-date=10 December 2023 |website=STAT |archive-date=9 December 2023 |archive-url=https://web.archive.org/web/20231209102125/https://www.statnews.com/2023/12/08/fda-approves-casgevy-crispr-based-medicine-for-treatment-of-sickle-cell-disease/ |url-status=live }} The cost effectiveness threshold of the therapy in the US is estimated to be between $1.35 million and $2.05 million{{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/ |url-status=live |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/ |archive-date=4 December 2023 |access-date=4 December 2023 |website=Institute for Clinical and Economic Review}} depending on perspective (healthcare vs limited societal) and assuming the willingness to pay for 1 quality-adjusted life year (QALY) at $100,000–$150,000.{{Cite web |title=Value Assessment Framework |url=https://icer.org/our-approach/methods-process/value-assessment-framework/ |access-date=10 December 2023 |website=Institute for Clinical and Economic Review |archive-date=14 November 2023 |archive-url=https://web.archive.org/web/20231114183927/https://icer.org/our-approach/methods-process/value-assessment-framework/ |url-status=live }}
The UK price is estimated to be {{GBP|1 million}}.{{Cite news |vauthors=Pinkstone J, Searles M |date=16 November 2023 |title=Life-changing blood disease treatment approved at £1m cost per patient |work=The Telegraph |url=https://www.telegraph.co.uk/news/2023/11/16/gene-therapy-blood-disorders-sickle-cell-approved-uk-mhra/ |access-date=10 December 2023 |archive-date=10 December 2023 |archive-url=https://web.archive.org/web/20231210220429/https://www.telegraph.co.uk/news/2023/11/16/gene-therapy-blood-disorders-sickle-cell-approved-uk-mhra/ |url-status=live }}{{cite journal | vauthors = Wong C | title = UK first to approve CRISPR treatment for diseases: what you need to know | journal = Nature | volume = 623 | issue = 7988 | pages = 676–677 | date = November 2023 | pmid = 37974039 | doi = 10.1038/d41586-023-03590-6 | title-link = doi | doi-access = free | bibcode = 2023Natur.623..676W }}
References
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Further reading
{{refbegin}}
- {{cite journal | vauthors = Frangoul H, Locatelli F, Bhatia M, Mapara MY, Molinari L, Sharma A, Lobitz S, de Montalembert M, Rondelli D, Steinberg M, Walters MC | display-authors = 6 |title=Efficacy and Safety of a Single Dose of Exagamglogene Autotemcel for Severe Sickle Cell Disease |journal=Blood |date=November 2022 |volume=140 |issue=Supplement 1 |pages=29–31 |doi=10.1182/blood-2022-162353|s2cid=254352365 |doi-access=free }}
- {{cite journal | vauthors = Locatelli F, Lang P, Li A, Corbacioglu S, de la Fuente J, Wall DA, Liem R, Meisel R, Mapara MY, Shah AJ, Cappellini MD, Kattamis A, Sheth S, Bobruff Y, Bower L, Zhang L, Sharma A, Song Y, Hobbs W, Frangoul H | display-authors = 6 |title=Efficacy and Safety of a Single Dose of Exagamglogene Autotemcel for Transfusion-Dependent β-Thalassemia |journal=Blood |date=November 2022 |volume=140 |issue=Supplement 1 |pages=4899–4901 |doi=10.1182/blood-2022-166881|s2cid=256788715 |doi-access=free }}
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External links
- {{cite web | title=Exagamglogene Autotemcel (Code C169042) | website=NCI Thesaurus | url=https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=ncit&code=C169042 }}
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