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.
Contents
History
The treatment was developed at San Raffaele Telethon Institute for Gene Therapy (SR-Tiget) and developed by GlaxoSmithKline (GSK) through a 2010 collaboration with Fondazione Telethon and Ospedale San Raffaele (OSR). 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.
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. 75% of people who received the treatment needed no further enzyme replacement therapy. Efforts had begun 14 years before. The total number of children treated was reported as 22 and 18. Around 80% of patients have no matched donor. Strimvelis was approved by the European Commission on 27 May 2016.
As of 2016, the only site approved to manufacture the treatment was MolMed.
Society and culture
The condition affects about 14 people per year in Europe and 12 in the U.S.
The price for the treatment was set at €594k, 2 times the annual cost of enzyme replacement therapy injections. enzyme replacement therapy for ADA requires weekly injections and costs about $4.25 million for one patient over 10 years.
Treatment
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. As of April 2016, the transduced cells had a shelf life of about six hours.
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 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.
Side effects
The most common side effects in clinical trials were pyrexia, increased liver enzyme levels, anemia, neutropenia, hemolytic anaemia, aplastic anaemia and thrombocytopenia.