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| Trade names | Strimvelis |
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| Routes of administration | Intravenous |
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Autologous CD34+ enriched cell fraction that contains CD34+ cells transduced with retroviral vector that encodes for the human ADA cDNA sequence, sold under the brand name Strimvelis, is a medication used to treat severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID).[1]
ADA-SCID is a rare inherited condition in which there is a change (mutation) in the gene needed to make an enzyme called adenosine deaminase (ADA).[1] As a result, people lack the ADA enzyme.[1] Because ADA is essential for maintaining healthy lymphocytes (white blood cells that fight off infections), the immune system of people with ADA-SCID does not work properly and without effective treatment they rarely survive more than two years.[1]
Strimvelis is the first ex vivo autologous gene therapy approved by the European Medicines Agency (EMA).[2]
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Adenosine Deaminase Deficiency | SCID | Lecture 8
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ada scid
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A Stem Cell Cure for Bubble Baby Disease (SCID)
Transcription
Medical uses
Strimvelis is indicated for the treatment of people with severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID), for whom no suitable human leukocyte antigen (HLA)-matched related stem cell donor is available.[1]
Treatment
The treatment is personalized for each person; hematopoietic stem cell (HSCs) are extracted from the person and purified so that only CD34-expressing cells remain. Those cells are cultured with cytokines and growth factors and then transduced with a gammaretrovirus containing the human adenosine deaminase gene and then reinfused into the person. These cells take root in the person's bone marrow, replicating and creating cells that mature and create normally functioning adenosine deaminase protein, resolving the problem.[3][4][5] As of April 2016, the transduced cells had a shelf life of about six hours.[6]
Prior to extraction, the person is treated with granulocyte colony-stimulating factor in order to increase the number of stem cells and improve the harvest; after that but prior to reinfusion, the person is treated with busulfan or melphalan to kill as many of the person's existing HSCs to increase the chances of the new cells' survival.[4][5]
Side effects
The most common side effect is pyrexia (fever).[1]
Serious side effects may include effects linked to autoimmunity (when the immune system attacks the body's own cells) such as hemolytic anemia (low red blood cell counts due to their too rapid breakdown), aplastic anemia (low blood cell counts due to damaged bone marrow), hepatitis (liver inflammation), thrombocytopenia (low blood platelet count) and Guillain-Barré syndrome (damage to nerves that can result in pain, numbness, muscle weakness and difficulty walking).[1]
Leukemia is a risk of treatment with Strimvelis.[7]
History
The treatment was developed at San Raffaele Telethon Institute for Gene Therapy and developed by GlaxoSmithKline (GSK) through a 2010 collaboration with Fondazione Telethon and Ospedale San Raffaele. GSK, working with the biotechnology company MolMed S.p.A., developed a manufacturing process that was previously only suitable for clinical trials into one demonstrated to be robust and suitable for commercial supply.[8][9]
Strimvelis, the first ex vivo autologous gene therapy approved by the EMA, has demonstrated remarkable efficacy and safety in clinical trials for the treatment of ADA-SCID.[10]
In April 2016, a committee at the European Medicines Agency (EMA) recommended marketing approval for its use in children with adenosine deaminase deficiency, for whom no matched HSC donor is available, on the basis of a clinical trial that produced a 100% survival rate; the median follow-up time was 7 years after the treatment was administered.[3] 75% of people who received the treatment needed no further enzyme replacement therapy.[11] Efforts had begun 14 years before. The total number of children treated was reported as 22[12] and 18.[13] Around 80% of patients have no matched donor.[14] Strimvelis was approved [15] by the European Commission on 27 May 2016.
As of 2016,[update] the only site approved to manufacture the treatment was MolMed.[6]
In 2016, Strimvelis obtained Marketing Authorization in Europe while under GSK holding.[16]
In 2017, GSK announced it was looking to sell off Strimvelis,[17] and in March 2018, GSK sold Strimvelis to Orchard Therapeutics Ltd.; as of that time there had been only five sales of the product.[18]
As of 2023,[update] the product has been licensed in Iceland, Norway, Liechtenstein, and the UK.[16]
Society and culture
The condition affects about 14 people per year in Europe and 12 in the U.S.[19]
Economics
The price for the treatment was set at €594,000, twice the annual cost of enzyme replacement therapy injections.[20] Enzyme replacement therapy for ADA requires weekly injections and costs about US$4.25 million for one patient over ten years.[14]
Names
Strimvelis is the brand name.[3] The common name is autologous CD34+ enriched cell fraction that contains CD34+ cells transduced with retroviral vector that encodes for the human ADA cDNA sequence.[3]
References
- ^ a b c d e f g h "Strimvelis EPAR". European Medicines Agency (EMA). 17 September 2018. Archived from the original on 8 October 2023. Retrieved 11 June 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
- ^ "Pipeline". Orchard Therapeutics. 2 July 2021. Archived from the original on 15 June 2021. Retrieved 5 July 2021.
- ^ a b c d "Strimvelis" (PDF). European Medicines Agency (EMA). Archived (PDF) from the original on 24 June 2019. Retrieved 13 April 2016.
- ^ a b Candotti F (April 2014). "Gene transfer into hematopoietic stem cells as treatment for primary immunodeficiency diseases". International Journal of Hematology. 99 (4): 383–92. doi:10.1007/s12185-014-1524-z. PMID 24488786. S2CID 8356487.
- ^ a b Touzot F, Hacein-Bey-Abina S, Fischer A, Cavazzana M (June 2014). "Gene therapy for inherited immunodeficiency". Expert Opinion on Biological Therapy. 14 (6): 789–98. doi:10.1517/14712598.2014.895811. PMID 24823313. S2CID 207483238.
- ^ a b Ben Adams for FierceBiotech 4 April 2016 Strimvelis to be the start of a whole new gene therapy platform for GSK and partners Archived 14 April 2016 at the Wayback Machine
- ^ "Orchard Statement on Strimvelis, a Gammaretroviral Vector-Based Gene Therapy for ADA-SCID". Orchard Therapeutics (Press release). 30 October 2020. Archived from the original on 9 July 2021. Retrieved 5 July 2021.
- ^ "GSK receives positive CHMP opinion in Europe for Strimvelis™, the first gene therapy to treat very rare disease, ADA-SCID" (Press release). London: GSK. 1 April 2016. Archived from the original on 6 February 2024. Retrieved 8 March 2024.
- ^ "GSK and MolMed sign immunodeficiency deal". 9 August 2011. Archived from the original on 6 February 2024. Retrieved 8 March 2024.
- ^ Papaioannou I, Owen JS, Yáñez-Muñoz RJ (August 2023). "Clinical applications of gene therapy for rare diseases: A review". Int J Exp Pathol. 104 (4): 154–176. doi:10.1111/iep.12478. PMC 10349259. PMID 37177842.
- ^ Booth C, Gaspar HB, Thrasher AJ (April 2016). "Treating Immunodeficiency through HSC Gene Therapy" (PDF). Trends in Molecular Medicine. 22 (4): 317–327. doi:10.1016/j.molmed.2016.02.002. PMID 26993219. Archived (PDF) from the original on 24 July 2018. Retrieved 8 March 2024.
- ^ Roland D (1 April 2016). "Glaxo's Potential Cure for "Bubble Boy Disease" One Step Closer". The Wall Street Journal. Archived from the original on 20 January 2017. Retrieved 11 March 2017.
- ^ Ward A (1 April 2016). "GSK to allow staggered payments for EMA-approved gene therapy". The Financial Times. Archived from the original on 8 March 2024. Retrieved 13 April 2016.
- ^ a b Gokhale K (1 April 2016). "Glaxo's 'Bubble Boy' Gene Therapy Wins EU Drug Agency Nod". Bloomberg News. Archived from the original on 31 July 2016. Retrieved 11 March 2017.
- ^ "StrimvelisTM receives European marketing authorisation to treat very rare disease, ADA-SCID - GSK". Archived from the original on 1 August 2016. Retrieved 22 July 2016.
- ^ a b Fratini ES, Migliavacca M, Barzaghi F, Fossati C, Giannelli S, Monti I, et al. (2023). "Hemophagocytic inflammatory syndrome in ADA-SCID: report of two cases and literature review". Front Immunol. 14: 1187959. doi:10.3389/fimmu.2023.1187959. PMC 10331599. PMID 37435083.
- ^ "GSK gives up on rare diseases as gene therapy gets two customers". Reuters. 26 July 2017. Archived from the original on 11 September 2018. Retrieved 11 September 2018.
- ^ Paton J (6 March 2018). "Tiny U.K. Biotech Takes On Glaxo's $730,000 Gene Therapy". Bloomberg. Archived from the original on 11 September 2018. Retrieved 11 September 2018.
- ^ Regalado A (6 May 2016). "Gene Therapy's First Out-and-Out Cure Is Here". MIT Technology Review. Archived from the original on 19 September 2020. Retrieved 12 May 2016.
- ^ "Does the EU price of Strimvelis create a new 'glass ceiling'? - groupH - Comment =". www.grouph.com. November 2016. Archived from the original on 20 July 2017. Retrieved 26 February 2017.
Further reading
- "Strimvelis for treating adenosine deaminase deficiency–severe combined immunodeficiency". NICE. 7 February 2018. Archived from the original on 18 December 2023. Retrieved 8 March 2024.
- Aiuti A, Roncarolo MG, Naldini L (June 2017). "ex vivo gene therapy in Europe: paving the road for the next generation of advanced therapy medicinal products". EMBO Molecular Medicine. 9 (6): 737–740. doi:10.15252/emmm.201707573. PMC 5452047. PMID 28396566.
- South E, Cox E, Meader N, Woolacott N, Griffin S (June 2019). "® for Treating Severe Combined Immunodeficiency Caused by Adenosine Deaminase Deficiency: An Evidence Review Group Perspective of a NICE Highly Specialised Technology Evaluation". PharmacoEconomics - Open. 3 (2): 151–161. doi:10.1007/s41669-018-0102-3. PMC 6533345. PMID 30334168.
This page was last edited on 8 March 2024, at 03:15