New hope for children with the ultra-rare immune disorder ADA-SCID: Gene therapy Strimvelis recommended for approval by EMA’s CHMP

Last Updated on

April 02, 2016 – The European Medicines Agency (EMA) has recommended granting a marketing authorisation in the European Union (EU) for a new gene therapy for the treatment of patients with adenosine-deaminase-deficient severe combined immunodeficiency (ADA-SCID), who have no matching donor for a stem cell transplant. Children born with this disorder have virtually no immunity to fight off everyday bacterial, fungal or viral infections.

ADA-SCID is an ultra-rare immune disorder, caused by a faulty gene inherited from both parents that stops the production of adenosine deaminase. Without this enzyme, the body is unable to break down a toxic substance called deoxyadenosine. The toxin builds up and destroys infection-fighting

Autosomal recessive pattern of inheritance of a chromosome carrying a faulty gene, labeled in orange in the present illustration.

Autosomal recessive pattern of inheritance of a chromosome carrying a faulty gene, labeled in orange in the present illustration.

lymphocytes. Children born with ADA-SCID are severely impaired in their ability to fight infections. The disorder can also lead to various non-immunological health problems, including a failure to grow and develop normally, hearing loss and liver and kidney problems. Symptoms normally appear in the first six months of life. The disease is usually fatal in the first two years of life, unless the function of the immune system can be restored.

There is no authorised medicine to treat ADA-SCID in the EU. Transplantations of blood-forming stem cells from the bone marrow of a healthy person have been conducted, but the success of this treatment depends on how close is the match between the stem-cell donor and the patient. Typically, ADA-SCID sufferers who receive stem cell transplants from genetically-matched siblings have a good chance of survival and recovery of the immune system. However, survival of patients who have no related matched donor is poor, mainly because of the risk of graft versus host disease, whereby the T-cells in the donated tissue attack the body cells of the recipient. This requires immunosuppressant treatment and increases the risk of infection, the main cause of death after transplantation.

Some patients received enzyme replacement therapy with pegylated adenosine deaminase (PEG-ADA) on a compassionate use basis, although this treatment is not authorised anywhere in the EU. Enzyme replacement requires lifelong weekly injections. Based on the experience so far, there appears to be a loss in immune function over time in patients receiving PEG-ADA, making them again more susceptible to infections.

Gene therapy could offer an alternative treatment with better prognosis for patients without a suitable transplant donor. Strimvelis is manufactured from a patient’s own immature bone marrow cells (called CD34+ cells) into which a normal adenosine deaminase enzyme gene has been inserted. After these cells are injected back into the patient, the cells are able to develop into the different types of blood and immune cells. This is expected to give the patient life-long ability to produce lymphocytes that can fight off infections.

Using a patient’s own cells avoids the risk of graft versus host disease, and lowers the risk of infections due to immunosuppression. It also reduces the dose of chemotherapy needed to prepare a patient for treatment compared to bone marrow transplant. Furthermore, gene therapy is not dependent upon a donor search, so it can be made available to any patient.

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 pyrexia (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), EMA’s specialised scientific committee for advanced therapy medicinal products, such as gene or cell therapies. 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.

Strimvelis was designated as an orphan medicinal product in 2005. Orphan designationgives medicine developers access to incentives such as fee reductions for scientific advice, or the possibility to obtain 10 years’ market exclusivity for an authorised orphan-designated medicine. It is a key instrument available in the EU to encourage the development of medicines for patients with rare diseases. The applicant received scientific advice from the Agency on various aspects of the application dossier throughout the medicine’s development.

The opinion adopted by the CHMP at its March 2016 meeting is an intermediary step on Strimvelis’ path to patient access. The CHMP opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorisation. Once a marketing authorisation has been granted, decisions about price and reimbursement will take place at the level of each Member State, taking into account the potential role/use of this medicine in the context of the national health system of that country.

Tags: , , , , , , , ,
About the Author
thassodotcom Ph.D.; Professor in Pharmacology and Toxicology. Senior expert in theragenomic and personalized medicine and individualized drug safety. Senior expert in pharmaco- and toxicogenetics. Senior expert in human safety of drugs, chemicals, environmental pollutants, and dietary ingredients.

Your opinion


No comments yet

thasso: conditions

thasso: tweets

thasso post: magazine

View my Flipboard Magazine.

thasso: categories

thasso: archives

thasso: simple chat

You must be a registered user to participate in this chat.

  • Scientists highlight potential of exposome research January 23, 2020
    Over the last two decades, the health sciences have been transformed by genomics, which has provided insights into genetic risk factors for human disease. While powerful, the genomics revolution has also revealed the limits of genetic determinants, which account for only a fraction of total disease risk. A new article in the journal Science argues […]
  • Researchers uncover mechanism for how common gene therapy vectors enter cells January 23, 2020
    Researchers led by a team at Massachusetts Eye and Ear have identified a novel cellular entry factor for adeno-associated virus vector (AAV) types—the most commonly used viral vectors for in vivo gene therapy. AAVs are vectors—or vehicles—that are created from a virus that is made harmless by molecular engineering, and have shown promise transporting genetic […]
  • Largest-ever study ties over 100 genes to autism January 23, 2020
    More than 100 genes appear to be involved in autism spectrum disorders (ASD), according to the largest genetic study of the condition to date.
  • Researchers uncover the genomics of health January 23, 2020
    Most diseases have a genetic component. To better understand disease, researchers led by the Garvan Institute of Medical Research are analysing genetic information to determine what keeps us healthy.
  • Study explores cognitive function in people with mental illness January 22, 2020
    A study funded by the Veterans Administration and directed by researchers at the University of Miami Miller School of Medicine has shown few differences in the profiles of genes that influence cognition between people with schizophrenia, bipolar disorder and the general population. This surprising finding could provide new insights into therapies designed to improve cognition. […]
  • Lung microbiome may help predict outcomes in critically ill patients January 24, 2020
    Changes in the lung microbiome may help predict how well critically ill patients will respond to care, according to new research published online in the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.
  • NIH study finds benefits of fetal surgery for spina bifida persist through school age January 24, 2020
    Children as young as 6 years old who underwent fetal surgery to repair a common birth defect of the spine are more likely to walk independently and have fewer follow-up surgeries, compared to those who had traditional corrective surgery after birth, according to researchers funded by the National Institutes of Health.
  • What goes up may actually be down January 24, 2020
    A new study in Frontiers in Neuroscience used virtual reality to determine how people plan their movements by 'seeing' gravity using visual cues in the landscape around them, rather than 'feeling it' through changes in weight and balance.
  • Benefits of fetal surgery for spina bifida persist in school-age children January 24, 2020
    In a follow-up to the landmark 2011 study that demonstrated prenatal surgery for spina bifida has measurable benefits over surgery after birth for one of the most disabling neural tube defects, researchers have published new findings. These findings show significant physical and emotional benefits a decade later in school-age children who received corrective surgery in […]
  • Benefits of fetal surgery for spina bifida continue through school age January 24, 2020
    The benefits of fetal surgery to repair spina bifida, a procedure pioneered at Vanderbilt University Medical Center (VUMC) in 1997, continue through school age, a National Institutes of Health (NIH) study reports today in the journal Pediatrics.