On Friday 27th May, GlaxoSmithKline (GSK) received approval from the European Commission to market their landmark ADA-SCID gene therapy drug for a rare genetic disorder in children across Europe. The drug, Strimvelis, is the first ever gene therapy drug that promises treatments for children suffering from a life-limiting disease called adenosine deaminase severe combined immunodeficiency (ADA-SCID). This breakthrough work has been carried out by GSK in collaboration with Italian firms, Fondazioine Telethon and Ospedale San Raffaele.

Strimvelis has come as the second approved gene therapy drug after Glybera in Europe. Glybera, from uniQure, was approved in 2012 and treated lipoprotein lipase deficiency in patients. However, the drug development of Strimvelis, being associated with one of the biggest pharmaceutical companies, will have a global impact magnified manifold.

Earlier this year in April, GSK got a positive feedback from the Medicinal Products for Human Use (CHMP) of the European Medicines (EMA) along with the Committee for Advanced Therapies (CAT) that recommended granting of marketing authorization for the drug. As this recommendation was soon followed by a grant approval from EU, this could be seen as a milestone towards revolutionizing treatment strategies for many genetic diseases.

What Is ADA-SCID?

ADA-SCID is a rare immunodeficiency disease in which a child’s immune system is highly compromised. This rare disease is estimated to affect 1 in every 200,000 newborns worldwide. The condition occurs when the ADA gene is mutated. This gene encodes the enzyme adenosine deaminase.

While this enzyme may be involved in different functions, it is most active in the functioning of lymphocytes. Due to this genetic aberration, the combined absence of T-lymphocyte and B- lymphocyte functioning makes the child vulnerable against pathogenic invasion. Children born with ADA-SCID easily fall prey to bacterial, viral or fungal infections.

The infections can persistent for a longer duration. A particular infection can keep coming back otherwise comorbidity of infections is commonly observed in children with ADA-SCID. With increased severity of infections, children get seriously ill and most children with this condition cannot live past their second birthday. These children commonly suffer from pneumonia, skin rashes and chronic diarrhea. As they grow up, serious pulmonary infections, malnutrition and other life threatening medical conditions may be faced.

How Does The ADA-SCID Gene Therapy Drug Work?

Strimvelis is an ex-vivo stem cell gene therapy that makes use of hematopoietic stem cells extracted from the bone marrow of the patient. The drug is administered only once in a lifetime and it does not require any third party donor. As a third party donor is not required in this therapy, the risk of graft-versus-host disease is eliminated altogether.

In graft-versus-host disease, the complications in the treatment increase when the recipient’s immune system rejects the donor’s cells and an immune response is triggered against these cells. To reduce the cell rejection, health professionals administer immunosuppressant drugs. This, however makes a person prone to catching other pathogenic infections. To counteract these complications, the mode of action used for Strimvelis is safe.

In this procedure, the extracted stem cells that carry the faulty gene are treated in a laboratory setting and reintroduced into the patient via IV infusion. A vector is used that carries the corrected pair of genes into the system of the patient. As the vector carrying the cells with modified genes is injected back into the patients’ system, low doses of chemotherapy are also administered. The use of chemotherapy eliminates the remaining diseased cells in the system. Once the diseased cells are eliminated from the system, the newly replenished normal cells take up the task of producing correct proteins.

During the clinical trials of Strimvelis, a 100% success rate was observed. 18 children were given the drug in the pivotal study. In follow-up visits stretching up to 7 years’ time, the children’s immune system was found to be functioning normally, with all the children being alive till date.

Experts have long been trying to make use of gene therapy to treat genetic diseases permanently. However, this has been a rocky journey for experts who have been working in the field of gene therapy for years.

It was in 1999 when the first clinical trial for gene therapy took place. The unforeseen complications led to the death of the 18-year old patient who suffered from a serious liver disease. The initial clinical trials were met with fatal complications like activation of oncogenes or the reaction of the body’s immune system to the viral particle used as vectors.

Due to these discouraging results of the initial efforts, big pharmaceutical companies decided not to further invest their time, money and energy in this unyielding cause. But with this breakthrough, from a big pharmaceutical company such as GSK, other prominent pharmaceutical companies will be encouraged to resume their efforts for the formulation of gene therapy drugs for various genetic diseases such as muscular dystrophy, cystic fibrous, Huntington’s disease and dozens of other rare genetic conditions.

One of the pioneers of gene therapy development, Prof Alan Boyd, has welcomed this drug approval and commented, “Most of the hard work has been done by small companies. But as some of these products have come closer to market, Big Pharma has come back in.”

When being asked about the drug piece, R&D president at GSK, Mr. Patrick Vallance said, “We are absolutely committed to getting the price right. It’s obvious that you can’t charge a price that is unaffordable.”

After receiving drug marketing approval, the drug has taken a stride forward and will soon reach clinical practices in Europe. While the FDA has yet not given approval to Strimvelis, we will only be able to look at the fate of Strimvelis from different aspects in the coming times.