A new gene therapy approved!

This week GSK’s ex vivo gene therapy for ADA-SCID received its marketing authorization from the European Medicine Agency. This is awesome news for the medical world and patients.


What is ADA-SCID?

ADA-SCID a disease characterized by a failure of the immune system evident by a lack of or malfunctioning B and T cells and is colloquially referred to as ‘bubble-boy disease’ Whereas SCID can be caused by a number of genetic mutations, ADA-SCID is a result of a mutation in gene coding for the adenosine deaminase (ADA). ADA-SCID accounts for 10-20% of all SCID cases. Individuals with SCID are at risk to life-threatening infections. It follows an autosomal recessive pattern meaning that you have a 25% child getting it if both parents are carriers.

ADA is responsible for purine metabolism. Without it results in the toxic accumulation of metabolites that primarily affect lymphocyte development and function. Given ADA is also expressed in a number of other tissues, individuals also experience other complications such as motor function deficits, skeletal dysplasia, liver dysfunction to name a few.

Current treatment for ADA-SCID is patient isolation, bone marrow transplant (BMT) to reseed a functional immune system, antibiotics, antifungals, and enzyme replacement therapy (i.e.injections of ADA) (ERT). ERT is primarily used as an acute therapy while patients await BMT. Survival post-BMT is good for those that are a donor match and poor for those that aren’t.  Additionally, over the past two decades patients have had to promising gene therapy approaches through clinical trials.

ADA-SCID is very rare i.e. 1 in 200,000 to 1 in 1,000,000 new cases per year. Patients are typically diagnosed in infancy and will die before their birthday without treatment.

What is Strimvelis?

Strimvelis is an autologous ex vivo stem cell gene therapy. The patients hematopoietic stem cells are harvested from the bone marrow, are genetically modified through the insertion of a functional copy of the ADA gene into the host cell genome using a gamma retroviral vector. These transduced cells are capable of making the ADA enzyme and are re-infused back into the patient intravenously. GSK2696273 has been approved by the European’s Medicine Agency to treat patients who have ADA-SCID for whom no suitable human leukocyte antigen (HLA)-matched related stem cell donor is available.

Of the 18 patients treated in clinical trials with Strimvelis all are still alive after a median follow up of 6.9 years. More so there have experienced a significant reduction serious infections through the reconstitution of their immune systems.



Why is it a big deal?

It’s been a long road to say the least. ADA-SCID was the first successful gene therapy to be trialed in humans in 1990. The first patient to be treated is still alive today. However the development of leukemia in 5 out of the 20 boys that received gene therapy for XL-SCID (another form of SCID) (4 were cured) and the death of a patient in a another trial for another disease put a hold to clinical trials. With this came a retraction of investment into the space. Following years of research and development into next-gen vector designs and further clinical trials, the promise of gene therapy was reignited towards the end of the 2000s. Strimvelis represents the first corrective gene therapy for children in the world. It is the second gene therapy product approved by the EMA, the first being Glybera for lipoprotein lipase deficiency.

What’s next?

There are two aspects of this therapy that I will watch closely:

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