Strimvelis

Strimvelis (GSK 2696273) is a treatment in development for adenosine deaminase deficiency, a form of severe combined immunodeficiency.[1]

The treatment is personalized for each person who will receive it; 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 transfected with a gammaretrovirus containing the human adenosine deaminase gene, and then given back to 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.[2][3][4] As of April 2016, the transfected cells had a shelf life of about six hours.[5]

Prior to the the HSCs being extracted, the person is first treated with granulocyte colony-stimulating factor in order to increase the number of stem cells in the person and improving the harvest; after that but prior to the treatment being administered, the person is treated with busulfan or melphalan to kill off as many of the person's existing HSCs to increase the chances of the new cells' survival.[2][4]

The most common side effects in clinical trials have been pyrexia, increased liver enzyme levels, anemia, neutropenia, hemolytic anaemia, aplastic anaemia, and thrombocytopenia.[3]

In April 2016, a committee at the European Medicines Agency recommended marketing approval for its use in children for whom no matched HSC donor is available, on the basis of a clinical trial in which there was 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.[6] These results were part of efforts by the Italian doctors that had begun 14 years before; the total number of children treated has been reported as 22[7] and 18.[8] Around 80% of children with the condition have no matched donor.[9]

As of 2016, the only site in the world approved to manufacture the treatment was at the Italian biotechnology company MolMed, which was started by scientists at Vita-Salute San Raffaele University,[10] and which had been collaborating with scientists there to develop the treatment.[5]

GlaxoSmithKline had licensed the intellectual property around the treatment in 2010, and GSK submitted the marketing application to the EMA.[7] As of April 2016 GSK said that it intended to improve the treatment to increase the shelf life of the transfected cells, and that it was also considering creating more centers where the treatment could be made. GSK also said at that time that it intended to use the underlying methods as a platform to develop treatments for other diseases.[7]

How much GSK would charge 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.[8] GSK said that it was considering various models for payment, including payments made over several years, and a risk-sharing program where payers get a refund if the treatment doesn't work.[9] The enzyme replacement therapy for ADA requires weekly injections and costs about $4.25 million for one patient over 10 years.[9]

References

  1. ↑ Adis Insight. GSK 2696273 Last updated Apr 6, 2016.
  2. 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
  3. 1 2 3 EMA Strimvelis Page accessed April 13, 2016
  4. 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
  5. 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
  6. ↑ Booth C et al. Treating Immunodeficiency through HSC Gene Therapy. Trends Mol Med. 2016 Apr;22(4):317-27. PMID 26993219
  7. 1 2 3 Denise Roland for the Wall Street Journal. April 1, 2016 Glaxo’s Potential Cure for “Bubble Boy Disease” One Step Closer
  8. 1 2 Andrew Ward for the Financial Times. April 1, 2016 GSK to allow staggered payments for EMA-approved gene therapy
  9. 1 2 3 Ketaki Gokhale for Bloomberg News. April 1, 2016 Glaxo's `Bubble Boy' Gene Therapy Wins EU Drug Agency Nod
  10. ↑ "MolMed Company Overview". The San Raffaele Biomedical Science Park.
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