Graft versus host disease, a potentially life-threatening complication, occurs more frequently and at greater severity when HSCT is performed with unrelated or less well-matched donors compared with MSD/MFDs. HSCT is potentially corrective for the immunological manifestations of ADA-SCID, but is recommended as first-line treatment only when a matched sibling/family donor (MSD/MFD) is available in order to achieve optimal immune reconstitution and overall survival. Treatment options include haematopoietic stem cell transplantation (HSCT), enzyme replacement therapy (ERT) and gene therapy. ĪDA-SCID can be fatal within the first year without treatment and requires early intervention. ADA deficiency is an ultra-rare immunodeficiency, with reported incidence rates of between 0.17 and 0.55 per 100,000 live births, translating to less than 50 children per year in the United States (US) and the European Union (EU). Diagnosis of SCID is usually made early in life, either through newborn screening (introduced in some states of the USA ) or after patients present with severe opportunistic infections, diarrhoea and a failure to thrive. Accumulation of toxic metabolites of purine nucleotides, normally metabolised by ADA, results in apoptosis in developing lymphocytes, absence of humoral and cellular immune function and severe combined immunodeficiency (SCID). Using practical and cost-efficient approaches, the Strimvelis registry is hoped to encourage further innovation in registry design within orphan drug development.Īdenosine deaminase (ADA) deficiency is a monogenic disorder of purine metabolism. Collaboration with partners is being sought to expand from a treatment registry into a disease registry. Strategies to ensure data completeness and patient retention in the registry will help fulfil pharmacovigilance requirements. 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. The Strimvelis registry sets a precedent for the safety monitoring of future gene therapies. 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. 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. 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. ResultsĪn observational registry has been established to monitor the safety and effectiveness of Strimvelis in up to 50 patients over a minimum of 15 years. Establishing individual investigator sites would be impractical and uneconomical owing to the small number of patients from each location receiving Strimvelis. 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. 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. Strimvelis (autologous CD34+ cells transduced to express adenosine deaminase ) 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.
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