GSK, Fondazione Telethon and Ospedale San Raffaele announce publication of pivotal safety and efficacy of gene therapy for children with ADA-SCID

Issued: London

GSK, Fondazione Telethon and Ospedale San Raffaeletoday 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.

Survival outcomes

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. 

Prof. Alessandro Aiuti, Principal Investigator, San Raffaele Telethon Institute for Gene Therapy, Milan, commented, “For children with ADA-SCID who do not have a matched related donor, alternative options include continuous enzyme replacement therapy or a bone marrow transplant from an unrelated or less well-matched donor. Transplants from these donors may cause graft vs host disease (GvHD) in some patients and other complications which can be fatal to the patients.  Strimvelis is based on a single administration of gene corrected stem cells taken from patient’s own bone marrow so there is no risk of GvHD. This work has been possible thanks to the efforts of dedicated investigators and collaborators over many years, in particular Prof. Maria Grazia Roncarolo, who set up the Paediatric Clinical Research Unit of SR-Tiget, and Prof. Fabio Ciceri, Head of the San Raffaele Stem Cell Programme”.

Dr. Maria Pia Cicalese, lead author of the paper reporting the study said, “This paper documents persistence of efficacy for several years, as well as appropriate growth and regular school attendance in most patients which is encouraging”.

Dr. Francesca Ferrua, co-lead author of the study said, “Making a decision on the most appropriate treatment option is highly emotional and challenging for parents, and we are grateful to the parents who participated to the study which allowed us to gain crucial information through several years of follow up”. 

Jonathan Appleby, PhD, and Medicines Development Leader, GSK, commented, “We are delighted to publish this formal update on the long-term safety and efficacy of Strimvelis.  This stem cell gene therapy is the first to have received a positive opinion in Europe. Although Strimvelis has been tested in clinical trials and independently judged to be appropriate for more widespread use by the Committee for Medicinal Products for Human Use (CHMP), it is very important that we follow patients over the long-term and that we will continue to update the medical community with the data so that patients and physicians can make appropriate treatment choices.”

Safety findings

Overall the safety findings in the study were in line with those expected in children with ADA-SCID who have undergone treatment with low-dose chemotherapy and who are undergoing immune recovery. Adverse events were reported for all 18 patients; the most frequently reported being usual childhood infections including upper respiratory tract infection, gastroenteritis and rhinitis.  Of the 39 serious adverse events which were reported post-GT, 62% were infections, with the most common being device-related infections, for example, from the central venous catheter (CVC) used during the treatment.  Five patients reported SAEs due to CVC infection, three due to gastroenteritis and three due to pneumonia.  A number of patients also experienced neurologic, CNS or hearing impairments which continued post-GT. No leukaemic events have been observed to date.

Study population and analyses

The results are an integrated dataset from 18 subjects enrolled via two pilot studies (n=3), one pivotal study (n=12) with a long-term follow up component and a compassionate use programme (n=3). 

Patients with ADA-SCID were eligible to be treated if they lacked a suitable human leukocyte antigen (HLA)-matched donor and had received more than six months of ERT but were not responding well to this treatment, or if ERT was not a long-term treatment option.  The patients, who included 11 boys and seven girls, came from a variety of countries and ethnic backgrounds.  The median age of treatment was under two years of age (1.7 years, ranging from 5 months to 6 years). In the pre-treatment phase, back-up stem cells were harvested and frozen as a precaution in case of poor engraftment or technical issues with the creation of the gene therapy.  Since ADA-SCID is estimated to occur in approximately 15 patients only per year in Europe and is a life threatening condition, all the studies within the data analysis were non-randomised, single-arm and open-label.  

Following treatment, reconstitution of the immune system was measured using a number of tests including normalisation of T cell subsets, ADA enzyme activity present in the child’s blood, function of T cells, antibody response to vaccination and decreased use of intravenous immunoglobulin (IVIg). 

The treatment process

The patient’s own bone marrow cells were removed under general anaesthesia, and a vector was used to insert a normal copy of the ADA gene into the cells (known as transduction). The gene-corrected cells were then re-introduced to the patient via an intravenous infusion, after which some of the cells homed back to the bone marrow.  In order to improve the engraftment of the gene-modified cells in the patient’s bone marrow, patients were also pre-treated with a low-dose of the chemotherapy Busulfan.

About the development of Strimvelis

The pivotal clinical study for Strimvelis was generated in a trial initiated at SR-Tiget in 2002, the sponsor for which was Fondazione Telethon. All patients were treated at Hospital San Raffaele in Milan and all medicinal product was made by MolMed S.p.A.  GSK was the financial sponsor from April 2012 onward and reported the findings from the study which remains ongoing.

Results of the study, including a full list of investigators, are available in the Blood journal.

About the GSK / Telethon / OSR collaboration

The gene therapy for the treatment of ADA-SCID was originally developed at the San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), a joint operation by Ospedale San Raffaele (OSR) and Fondazione Telethon (Telethon), and was taken forward by GSK through a strategic collaboration formed in 2010 between GSK, OSR and Telethon.  Within the partnership 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.

GSK – one of the world’s leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer.  For further information please visit  Strimvelis™ is a registered trademark of the GSK Group Companies.

Fondazione Telethon – Fondazione Telethon is a major biomedical charity in Italy whose mission is to advance biomedical research towards the cure of rare genetic diseases. Throughout its 26 years of activity, the Telethon Foundation has invested over €450 million in funding over 2,500 projects to study 470 diseases, involving more than 1,500 researchers. For further information, visit

Ospedale San Raffaele - Ospedale San Raffaele (OSR) is a clinical-research-university hospital established in 1971 to provide international-level specialised care for the most complex and difficult health conditions. Since 2012 OSR is part of Gruppo Ospedaliero San Donato, the leading hospital group in Italy.  The hospital is a multi-specialty centre with over 50 clinical specialties and has over 1,300 beds. Research at OSR focuses on integrating basic, translational and clinical activities to provide the most advanced care to our patients. For further information, visit:

San Raffaele Telethon Institute for Gene Therapy (SR-TIGET) - Based in Milan, Italy, the San Raffaele-Telethon Institute for Gene Therapy (SR-TIGET) is a joint venture between the Ospedale San Raffaele and Telethon.  SR-TIGET was established in 1995 to perform research on gene transfer and cell transplantation and translate its results into clinical applications of gene and cell therapies for different genetic diseases. For further information, visit