BACKGROUND: Strimvelis (autologous CD34+ cells transduced to express adenosine 
deaminase [ADA]) is the first ex vivo stem cell gene therapy approved by the 
European Medicines Agency (EMA), indicated as a single treatment for patients 
with ADA-severe combined immunodeficiency (ADA-SCID) who lack a suitable matched 
related bone marrow donor. Existing primary immunodeficiency registries are 
tailored to transplantation outcomes and do not capture the breadth of safety 
and efficacy endpoints required by the EMA for the long-term monitoring of gene 
therapies. Furthermore, for extended monitoring of Strimvelis, the young age of 
children treated, small patient numbers, and broad geographic distribution of 
patients all increase the risk of loss to follow-up before sufficient data have 
been collected. Establishing individual investigator sites would be impractical 
and uneconomical owing to the small number of patients from each location 
receiving Strimvelis.
RESULTS: An observational registry has been established to monitor the safety 
and effectiveness of Strimvelis in up to 50 patients over a minimum of 15 years. 
To address the potential challenges highlighted above, data will be collected by 
a single investigator site at Ospedale San Raffaele (OSR), Milan, Italy, and 
entered into the registry via a central electronic platform. Patients/families 
and the patient's local physician will also be able to submit healthcare 
information directly to the registry using a uniquely designed electronic 
platform. Data entry will be monitored by a Gene Therapy Registry Centre (funded 
by GlaxoSmithKline) who will ensure that necessary information is collected and 
flows between OSR, the patient/family and the patient's local healthcare 
provider.
CONCLUSION: The Strimvelis registry sets a precedent for the safety monitoring 
of future gene therapies. A unique, patient-focused design has been implemented 
to address the challenges of long-term follow-up of patients treated with gene 
therapy for a rare disease. Strategies to ensure data completeness and patient 
retention in the registry will help fulfil pharmacovigilance requirements. 
Collaboration with partners is being sought to expand from a treatment registry 
into a disease registry. Using practical and cost-efficient approaches, the 
Strimvelis registry is hoped to encourage further innovation in registry design 
within orphan drug development.