Strimvelis

Strimvelis is the first ex-vivo stem cell gene therapy to treat patients with a very rare disease called ADA-SCID (Severe Combined Immunodeficiency due to Adenosine Deaminase deficiency), a rare disorder caused by the absence of an essential protein called adenosine deaminase (ADA), which is required for the production of lymphocytes. Children born with ADA-SCID do not develop a healthy immune system so cannot fight off everyday infections, which results in severe and life-threatening illness. Without prompt treatment, the disorder often proves fatal within the child’s first year of life. ADA-SCID is estimated to occur in approximately 15 patients per year in Europe.

History

The treatment was initially developed at San Raffaele Telethon Institute for Gene Therapy (SR-Tiget) and developed by GlaxoSmithKline (GSK) through a strategic collaboration formed in 2010 with Fondazione Telethon and Ospedale San Raffaele (OSR). Within the collaboration GSK, working with the biotechnology company MolMed S.p.A, has applied its expertise in product development to optimise, standardise and characterise a manufacturing process that was previously only suitable for clinical trials into one that has been demonstrated to be robust and suitable for commercial supply.

In April 2016, a committee at the European Medicines Agency 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.[1] 75% of people who received the treatment needed no further enzyme replacement therapy.[2] These results were part of efforts that had begun 14 years before. The total number of children treated was reported as 22[3] and 18.[4] Around 80% of children with the condition have no matched donor.[5] Strimvelis has definitely been approved [6] by the European Commission on 27 May 2016.

As of 2016, the only site approved to manufacture the treatment was MolMed.[7]

Society and culture

The condition affects about 14 people per year in Europe and 12 in the U.S.[8]

The price for the treatment was unknown as of April 2016, but a comparable treatment is Glybera, the first gene therapy approved by European regulators in 2012, which costs about $1m per patient.[4] GSK said that it was considering payment models, including payments made over several years, and a risk-sharing program where payers get a refund if the treatment doesn't work.[5] The existing enzyme replacement therapy for ADA requires weekly injections and costs about $4.25 million for one patient over 10 years.[5]

Research

The treatment is personalized for each patient; hematopoietic stem cell (HSCs) are extracted from the patient 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 patient. 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.[1][9][10] As of April 2016, the transduced cells had a shelf life of about six hours.[7]

Prior to extraction, the patient 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 the reinfusion, the patient 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.[9][10]

The most common side effects in clinical trials have been pyrexia, increased liver enzyme levels, anemia, neutropenia, hemolytic anaemia, aplastic anaemia and thrombocytopenia.[1]

References

  1. 1 2 3 EMA Strimvelis Page accessed April 13, 2016
  2. ↑ Booth C et al. Treating Immunodeficiency through HSC Gene Therapy. Trends Mol Med. 2016 Apr;22(4):317-27. PMID 26993219
  3. ↑ Denise Roland for the Wall Street Journal. April 1, 2016 Glaxo’s Potential Cure for “Bubble Boy Disease” One Step Closer
  4. 1 2 Andrew Ward for the Financial Times. April 1, 2016 GSK to allow staggered payments for EMA-approved gene therapy
  5. 1 2 3 Ketaki Gokhale for Bloomberg News. April 1, 2016 Glaxo's `Bubble Boy' Gene Therapy Wins EU Drug Agency Nod
  6. ↑
  7. 1 2 Ben Adams for FierceBiotech Apr 4, 2016 Strimvelis to be the start of a whole new gene therapy platform for GSK and partners
  8. ↑ Regalado, Antonio (May 6, 2016). "Gene Therapy's First Out-and-Out Cure Is Here". MIT Technology Review. Retrieved 2016-05-12.
  9. 1 2 Candotti F. Gene transfer into hematopoietic stem cells as treatment for primary immunodeficiency diseases. Int J Hematol. 2014 Apr;99(4):383-92. Review. PMID 24488786
  10. 1 2 Touzot F, et al Gene therapy for inherited immunodeficiency. Expert Opin Biol Ther. 2014 Jun;14(6):789-98. doi: 10.1517/14712598.2014.895811. Epub 2014 Mar 8. Review. PMID 24823313
This article is issued from Wikipedia - version of the 11/18/2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.