The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA), in conjunction with the Committee for Advanced Therapies (CAT), has issued a positive opinion recommending marketing authorisation for GlaxoSmithKline's Strimvelis to treat patients with a very rare disease called ADA-SCID (severe combined immunodeficiency due to adenosine deaminase deficiency).

The medicine is a stem cell gene therapy created for an individual patient from their own cells which is intended to correct the root cause of the disease. If approved by the European Commission, the medicine - currently known as GSK2696273 (autologous CD34+ cells transduced to express ADA) - will be commercialised under the brand name Strimvelis, for the treatment of patients with ADA-SCID for whom no suitable human leukocyte antigen (HLA)-matched related stem cell donor is available.

The gene therapy for the treatment of ADA-SCID 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 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.

Patrick Vallance, president, R&D, GSK said, “We welcome this opinion from the CHMP which is an important step towards making Strimvelis available to the children living with this incredibly rare and fatal condition. Going forward, we hope to apply this gene therapy platform technology across other diseases, enabling many more patients to benefit from this innovative treatment approach.”

Martin Andrews, head of the rare disease unit at GSK said, “This positive opinion is a major milestone in GSK’s commitment to the development of innovative, transformative medicines. If approved, Strimvelis will become the first corrective ex-vivo gene therapy for children to achieve regulatory approval anywhere in the world. With our shared mission and complementary expertise we believe this collaboration will continue to deliver much needed new medicines for patients with rare genetic diseases.”

Until the EU commission decision, Strimvelis will remain an investigational gene therapy which is not approved for use anywhere in the world.

ADA-SCID is a very rare disorder caused by a faulty gene inherited from both parents. This faulty gene stops the production of an essential protein called adenosine deaminase (ADA), which is required for the production of lymphocytes (a type of white blood cell). Children born with ADA-SCID do not develop a healthy immune system so cannot fight off everyday infections, which results in severe and life-threatening illness. Without prompt treatment, the disorder often proves fatal within the child’s first year of life. ADA-SCID is estimated to occur in approximately 15 patients per year in Europe.

Replacing faulty hematopoietic (or ‘blood’) stem cells has been carried out in the form of bone marrow transplants for more than 40 years. However, these transplants rely on cells taken from an immune matched, or closely related, immune matched donor.  As immune (or HLA) matching is never perfect, immune incompatibility can cause rejection called graft versus host disease (GvHD).  GvHD is a common life threatening side effect that requires management with potent immunosuppressant medicines which in themselves increase the risk of infection and other complications.

Strimvelis is only administered once and does not rely on a third-party donor so there is no risk of GvHD.  The patient’s own bone marrow cells are removed, and a vector is used to insert a normal copy of the ADA gene into the cells. This step is known as transduction. The gene-corrected cells are then re-introduced to the patient via an intravenous infusion, after which some of the cells home back to the bone marrow.  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 chemotherapy.

Pivotal clinical study (n=12) and overall population treated within the primary data package (n=18)

A 100% survival rate at 3 years post-treatment with Strimvelis (primary endpoint) has been observed for all 12 children in the pivotal study, with 92% having interventional-free survival (i.e. did not require enzyme replacement therapy for a period of >3 months post-treatment or hematopoietic stem cell transplantation).  All 18 children treated with Strimvelis who contributed data to the marketing authorisation application are alive today with a median follow-up duration of approximately 7 years, with the first of these having received this gene therapy over 13 years ago. Interventional-free survival within the evaluable population (n=17) was 82%.

Overall the safety findings are in line with those expected in children with ADA-SCID who have undergone treatment with low-dose chemotherapy and who are undergoing immune recovery. A significant reduction in severe infections has been documented and no leukaemic events have been observed to date.

Fondazione Telethon – Telethon is a major biomedical charity in Italy whose mission is to advance biomedical research towards the cure of rare genetic diseases.

Ospedale San Raffaele 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 it is part of the San Donato Hospital Group, the leading hospital group in Italy.  The group includes 18 hospitals with a total of more than 5000 beds, 4000 physicians and treats 4 million patients per year.

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.