Date: 2016-05-26
Type of information: Granting of a Market Authorisation in the EU
Product name: Strimvelis™ - GSK2696273 (autologous CD34+ cells transduced to express adenosine deaminase)
Compound: autologous CD34+ cells transduced to express adenosine deaminase (ADA)
Therapeutic area: Rare diseases - Genetic diseases
Action mechanism:
- gene therapy. Strimvelis™ GSK2696273 is an autologous ex vivo stem cell gene therapy. Haematopoietic progenitor and stem cell of the patient (typically children) are harvested from the bone marrow in a hospital setting and then taken to a cell processing facility where they undergo a tightly controlled manufacturing process. Under this laboratory setting, a retrovirus (based upon the Moloney Murine Leukaemia Virus MoMLV) is used to enter cells and insert the corrected gene. The gene-corrected cells are then re-introduced to the patient via an intravenous infusion. This procedure takes about 1 week. In order to improve the engraftment of the gene-modified cells in the patient’s bone marrow, patients are also pre-treated with low dose busulfan (a chemotherapy). Recovery from busulfan can take 2 months, during which time the patient remains in hospital. When the gene-corrected cells are reintroduced to the patient and successful engraftment has taken place, the cells begin producing the ADA protein, thus restoring the patient’s ability to make lymphocytes which can then fight off infections. Using the patient’s own cells avoids the risk of immune-incompatibility, which is a common and life threatening complication associated with bone marrow transplant.
- This gene therapy was originally developed by Ospedale San Raffaele (OSR) and Fondazione Telethon (Telethon), through their joint San Raffaele Telethon Institute for Gene Therapy (SR-TIGET) 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 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.
- In April 2018, GSK has transfered its portfolio of approved and investigational rare disease gene therapies, including Strimvelis™, to Orchard Therapeutics.
- Strimvelis™ was designated as an orphan medicinal product in 2005.
Company: Orchard Therapeutics (UK)
Disease: adenosine deaminase severe combined immunodeficiency syndrome (ADA-SCID)
Latest news:
- • On April 1, 2016, the Committee for Medicinal Products for Human Use (CHMP) has recommended granting a marketing authorisation in the European Union (EU) for Strimvelis™ to treat patients with ADA-SCID (severe combined immunodeficiency due to adenosine deaminase deficiency), who have no matching donor for a stem cell transplant. The effects of Strimvelis™ were studied in a pivotal clinical trial involving 12 patients. All of the patients included in this trial are still alive, with an average follow-up period of 7 years. The most common side effects observed in this study include fever, increased hepatic enzyme levels, autoimmune reactions, such as anaemia, neutropenia, and autoimmune haemolytic anaemia, aplastic anaemia and thrombocytopenia. This study was carried out in accordance with a Paediatric Investigation Plan (PIP), which was agreed by the Agency’s Paediatric Committee. To ensure close long-term follow-up, the applicant for Strimvelis™, is required to enrol all patients who receive the medicines, in a registry to monitor and report its long-term effects.
The assessment of Strimvelis™ was carried out by the Committee on Advanced Therapies (CAT). At its March 2016 meeting, the CAT recommended the adoption of a marketing authorisation for Strimvelis. The CAT’s recommendation was considered by the Committee for Medicinal Products for Human Use (CHMP) which agreed with the CAT and issued a positive opinion.
- • On May 5, 2015, GSK, Fondazione Telethon (Telethon) and Ospedale San Raffaele (OSR) announced the submission of a marketing application to the European Medicines Agency (EMA) for a gene therapy (GSK2696273) to treat patients with a rare disease, adenosine deaminase severe combined immunodeficiency syndrome (ADA-SCID), for whom no suitable human leukocyte antigen (HLA)-matched related stem cell donor is available. The European Marketing Application is based on results from 18 children treated with the investigational gene therapy, twelve of whom were enrolled in a pivotal clinical trial conducted at San Raffaele Telethon Institute for Gene Therapy (TIGET). The first child was treated over thirteen years ago and all patients are alive today. Three of the eighteen patients required either long term (>3 month) enzyme replacement therapy or follow up bone marrow transplant. No significant tolerability events considered related to the gene therapy or leukemic events have been reported to date. Plans to publish data supporting the regulatory filing in a scientific peer-reviewed journal are in progress.
- The marketing application follows on from a strategic alliance formed in 2010 between GSK, OSR and Telethon. The alliance takes forward over 15 years of research performed at TIGET – one of the pioneers that successfully brought ex vivo gene therapy from pre-clinical studies to the treatment of patients. Since in-licensing the ADA-SCID gene therapy development programme in 2010, GSK – working with the biotechnology company MolMed S.p.A - optimised, characterised and validated both the vector and cell manufacturing methods. GSK also led regulatory plans, with support from TIGET investigators, to develop a marketing application by following standards described in the European Union for Advanced Therapy Medicinal Products. If approved, the gene therapy will first be made available at OSR in Milan, Italy with GSK as the marketing authorisation holder.
- ADA-SCID is the lead programme under the GSK/OSR/Telethon collaboration. Under the terms of the agreement, GSK has exclusive options to develop six further applications of ex vivo stem cell therapy, using the gene transfer technology developed by TIGET scientists. GSK has already exercised its option to develop two further programmes in rare diseases called metachromatic leukodystrophy (MLD) and Wiskott-Aldrich syndrome (WAS), which are both currently in clinical trials.
Patents:
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization:
UE authorization: 2016-05-26
Favourable opinion UE: 2016-04-01
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE:
OTC status:
Other news:
Is general: Yes
