The scale of SCIDNET ambition is that this will not be restricted:
a) to the EU, but will build models and practices that can be used globally and
b) to SCID, but the methods and technologies developed will be transferable to other rare and also common bone marrow disorders.
For monogenic diseases of the bone marrow, gene therapy has the potential to be a permanently curative therapy through gene transfer into self-renewing HSCs. The major ambition is now to perform studies that allow marketing authorisation application. In SCIDNET we have the opportunity in the LV ADA SCID study, to bring to licence one of the first curative gene therapy medicines. In current trials, patients have had to travel to the treatment site with resulting disruption and costs to family and healthcare. Furthermore, the need to infuse freshly transduced cells restricts the amount of conditioning that can be given and also does not allow for full characterisation of the transduced cell product before it is infused into patients. Our strategy of shipping cells to a central site, freezing gene corrected cells and shipping the product back to the patient bedside anywhere in Europe and ultimately the world, is unprecedented for gene therapy and will result in highly novel procedures and protocols.
The technologies and protocols that we adopt for the ADA SCID study will act as a paradigm and template for other gene therapy trials that follow, initially LV SCID-X1 and Artemis that will be part of the SCIDNET programme, but also RAG1/2 that may come after SCIDNET. However, our ambition is that this can become standard practice for future bone marrow gene therapy studies not just for the immune system but for a large number of other rare metabolic diseases as well as the more common haemoglobinopathies.
Economic and commercial impact
Gene therapy for SCID will considerably reduce healthcare costs for the treatment of this condition and potentially many others. Gene therapy for SCID-X1 and ADA-SCID is undertaken with minimal chemotherapy and most patients have a limited hospital stay of approximately 4-5 weeks, thereby considerably reducing in-patient treatment costs in comparison to a 20 week average stay for patients undergoing a fully conditioned procedure.
In addition to the reduced inpatient stay costs which may reduce costs by as much as 50%, a successful ADA SCID gene therapy outcome means that patients can stop highly expensive enzyme replacement therapy (approximate cost €400,000 per patient per year). Similarly, autologous stem cell gene therapy has the potential to off-set ERT for a number of other monogenic metabolic lysosomal disorders. In these other conditions (see Table 4) such as MPS-I and Pompe disease. A one-off autologous stem cell gene therapy procedure can be curative and can negate the lifelong requirement for this form of replacement therapy.
