Analysis of children with ADA-SCID and treated with autologous CD34+ cells known as Strimvelis is published in Blood- GSK

GSK, Fondazione Telethon and Ospedale San Raffaele announced the publication in BLOOD of the long-term safety and efficacy data from an analysis of 18 children with ADA-SCID treated with hematopoietic stem cell gene therapy between 2000 and 2010 at the San Raffaele Telethon Institute for Gene Therapy (SR-Tiget). Children with ADA-SCID, a very rare inherited disorder caused by a faulty gene, do not develop a healthy immune system which often proves fatal within the child’s first year of life.

The publication reports long-term outcomes in 18 patients treated with the investigational gene therapy (autologous CD34+ cells transduced to express ADA - now known as Strimvelis). The key efficacy endpoint for the analysis was survival. All 18 patients were alive after a median follow-up of 6.9 years (ranging from 2.3 to 13.4 years) at the data cut on 8th May 2014. Immune reconstitution was observed from six months post-treatment for the majority of patients, and was sustained over time as was the presence of cells containing the healthy ADA gene. In addition to overall survival, intervention-free survival and infection rates were also measured. Intervention-free survival was defined as survival without receiving a further stem cell transplant post-treatment with gene therapy (GT) or continuous enzyme replacement therapy (ERT) for more than three months. Fifteen of the 18 patients (83%) did not require these interventions. Three subjects required the re-introduction of ERT following treatment with GT, and two of those received a conventional BMT when an HLA-matched sibling was born.

The absolute number of severe infections seen post-GT was reduced when compared to the pre-treatment period (from 1.17 severe infections per patient year of observation to 0.26 severe infections per patient year up to three years post-GT, and dropping to 0.07 severe infections per patient year between four and eight years post-GT). Overall, for most patients, infection rates reduced over time in parallel with the reconstitution of the immune system. At the time of reporting, 12 out of 14 patients (86%) surveyed were attending pre-school/school as appropriate for their age.