Strimvelis Explained

Tradename:Strimvelis
Routes Of Administration:Intravenous
Atc Prefix:None
Legal Eu:Rx-only
Drugbank:DB16367

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). As a result, people lack the ADA enzyme. 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.

Strimvelis is the first ex vivo autologous gene therapy approved by the European Medicines Agency (EMA).[2]

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.

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.

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.

Side effects

The most common side effect is pyrexia (fever).

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).

Leukemia is a risk of treatment with Strimvelis.[6]

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.[7] [8]

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.[9]

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. 75% of people who received the treatment needed no further enzyme replacement therapy.[10] Efforts had begun 14 years before. The total number of children treated was reported as 22[11] and 18.[12] Around 80% of patients have no matched donor.[13] Strimvelis was approved [14] by the European Commission on 27 May 2016.

the only site approved to manufacture the treatment was MolMed.[15]

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]

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, twice the annual cost of enzyme replacement therapy injections.[20] Enzyme replacement therapy for ADA requires weekly injections and costs about for one patient over ten years.

Names

Strimvelis is the brand name. 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.

Further reading

Notes and References

  1. Web site: Strimvelis EPAR . 11 June 2020 . European Medicines Agency (EMA) . 17 September 2018 . 8 October 2023 . https://web.archive.org/web/20231008142429/https://www.ema.europa.eu/en/medicines/human/EPAR/strimvelis . live . Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  2. Web site: Pipeline . Orchard Therapeutics . 2 July 2021 . 5 July 2021 . 15 June 2021 . https://web.archive.org/web/20210615101210/https://www.orchard-tx.com/approach/pipeline/ . live .
  3. Web site: European Medicines Agency (EMA) . Strimvelis . 13 April 2016 . 24 June 2019 . https://web.archive.org/web/20190624043728/https://www.ema.europa.eu/en/documents/product-information/strimvelis-epar-product-information_en.pdf . live .
  4. Candotti F . 8356487 . Gene transfer into hematopoietic stem cells as treatment for primary immunodeficiency diseases . International Journal of Hematology . 99 . 4 . 383–92 . April 2014 . 24488786 . 10.1007/s12185-014-1524-z . free .
  5. Touzot F, Hacein-Bey-Abina S, Fischer A, Cavazzana M . 207483238 . Gene therapy for inherited immunodeficiency . Expert Opinion on Biological Therapy . 14 . 6 . 789–98 . June 2014 . 24823313 . 10.1517/14712598.2014.895811 .
  6. Orchard Statement on Strimvelis, a Gammaretroviral Vector-Based Gene Therapy for ADA-SCID . Orchard Therapeutics . 30 October 2020 . 5 July 2021 . 9 July 2021 . https://web.archive.org/web/20210709185410/https://ir.orchard-tx.com/news-releases/news-release-details/orchard-statement-strimvelisr-gammaretroviral-vector-based-gene . live .
  7. GSK receives positive CHMP opinion in Europe for Strimvelis™, the first gene therapy to treat very rare disease, ADA-SCID. 1 April 2016. London. GSK. 8 March 2024. 6 February 2024. https://web.archive.org/web/20240206012009/https://www.gsk.com/en-gb/media/press-releases/gsk-receives-positive-chmp-opinion-in-europe-for-strimvelis-the-first-gene-therapy-to-treat-very-rare-disease-ada-scid/. live.
  8. Web site: GSK and MolMed sign immunodeficiency deal . 9 August 2011 . 8 March 2024 . 6 February 2024 . https://web.archive.org/web/20240206012044/https://www.pmlive.com/pharma_news/gsk_and_molmed_sign_immunodeficiency_deal_323306 . live .
  9. Papaioannou I, Owen JS, Yáñez-Muñoz RJ . Clinical applications of gene therapy for rare diseases: A review . Int J Exp Pathol . 104 . 4 . 154–176 . August 2023 . 37177842 . 10349259 . 10.1111/iep.12478.
  10. Booth C, Gaspar HB, Thrasher AJ . Treating Immunodeficiency through HSC Gene Therapy . Trends in Molecular Medicine . 22 . 4 . 317–327 . April 2016 . 26993219 . 10.1016/j.molmed.2016.02.002 . free . 8 March 2024 . 24 July 2018 . https://web.archive.org/web/20180724005707/http://discovery.ucl.ac.uk/1481142/3/Booth_Treating%20Immunodeficiency%20through%20HSC%20Gene%20Therapy%20Figure%202.pdf . live .
  11. Web site: Denise . Roland . The Wall Street Journal . 1 April 2016 . Glaxo's Potential Cure for "Bubble Boy Disease" One Step Closer . 11 March 2017 . 20 January 2017 . https://web.archive.org/web/20170120112925/http://www.wsj.com/articles/glaxos-potential-cure-for-bubble-boy-disease-one-step-closer-1459525907 . live .
  12. Web site: Andrew . Ward . The Financial Times . 1 April 2016 . GSK to allow staggered payments for EMA-approved gene therapy . 13 April 2016 . 8 March 2024 . https://web.archive.org/web/20240308031511/https://www.ft.com/content/48f54b84-f7ef-11e5-96db-fc683b5e52db#axzz45j5rqAkB . live .
  13. Web site: Ketaki . Gokhale . Bloomberg News . 1 April 2016 . Glaxo's 'Bubble Boy' Gene Therapy Wins EU Drug Agency Nod . 11 March 2017 . 31 July 2016 . https://web.archive.org/web/20160731090159/http://www.bloomberg.com/news/articles/2016-04-01/glaxo-gene-therapy-for-rare-disease-wins-eu-drug-agency-backing . live .
  14. Web site: StrimvelisTM receives European marketing authorisation to treat very rare disease, ADA-SCID - GSK. 22 July 2016. 1 August 2016. https://web.archive.org/web/20160801135347/http://www.gsk.com/en-gb/media/press-releases/2016/strimvelistm-receives-european-marketing-authorisation-to-treat-very-rare-disease-ada-scid/. dead.
  15. Ben Adams for FierceBiotech 4 April 2016 Strimvelis to be the start of a whole new gene therapy platform for GSK and partners
  16. Fratini ES, Migliavacca M, Barzaghi F, Fossati C, Giannelli S, Monti I, Casiraghi M, Ferrua F, Recupero S, Consiglieri G, Calbi V, Tucci F, Gallo V, Bernardo ME, Cenciarelli S, Palmoni M, Moni M, Galimberti L, Duse M, Leonardi L, Sieni E, Soncini E, Porta F, Notarangelo LD, De Santis R, Ladogana S, Aiuti A, Cicalese MP . Hemophagocytic inflammatory syndrome in ADA-SCID: report of two cases and literature review . Front Immunol . 14 . 1187959 . 2023 . 37435083 . 10331599 . 10.3389/fimmu.2023.1187959. free .
  17. News: GSK gives up on rare diseases as gene therapy gets two customers . Reuters . 26 July 2017 . 11 September 2018 . 11 September 2018 . https://web.archive.org/web/20180911191405/https://www.reuters.com/article/us-gsk-results-rare-diseases-idUSKBN1AB2EE . live .
  18. News: Paton . James . Tiny U.K. Biotech Takes On Glaxo's $730,000 Gene Therapy . Bloomberg . 6 March 2018 . 11 September 2018 . 11 September 2018 . https://web.archive.org/web/20180911191413/https://www.bloomberg.com/news/articles/2018-03-06/tiny-biotech-takes-on-goliath-glaxo-s-730-000-gene-therapy . live .
  19. Web site: Gene Therapy's First Out-and-Out Cure Is Here. Regalado. Antonio. 6 May 2016. MIT Technology Review. 12 May 2016. 19 September 2020. https://web.archive.org/web/20200919082313/https://www.technologyreview.com/2016/05/06/160343/gene-therapys-first-out-and-out-cure-is-here/. live.
  20. Web site: Does the EU price of Strimvelis create a new 'glass ceiling'? - groupH - Comment =. November 2016. www.grouph.com. https://web.archive.org/web/20170720063404/http://grouph.com/does-the-eu-price-of-strimvelis-create-a-new-glass-ceiling/. 20 July 2017. 26 February 2017. live.

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