Gene Therapy for β-Thalassaemia Approaches European Market Approval

Tuesday, 16 April 2019

Gene therapy continues to evolve with new emerging treatments finally reaching its promised potential: providing a one-time lifelong cure for even the rarest and most severe of genetic disorders. IAPO member Thalassaemia International Federation explores this topic by highlighting the significant conditional approval for the first universal cure for the clinically most important type of thalassaemia, β-thalassaemia. 


The need for a cure

Thalassaemias are inherited diseases that reduce the ability of red blood cells to provide the body with oxygen. The diseases affect tens of thousands of patients worldwide and in their severest form and without adequate care are lethal in early childhood. Only a fraction of patients find compatible donors for a curative stem cell transplantation, while others require lifelong management with blood transfusions and medication, at inherent risks, substantial cost and overall reduced quality of life. Therefore researchers and clinicians have for decades been working towards a universal cure for thalassaemia patients.


Conditional marketing approval by the European Medicines Agency

Friday, 29th March 2019 was a significant date for thalassaemic patients in this quest, because it saw the conditional marketing approval in Europe of the first universal cure for the clinically most important type of thalassaemia, β-thalassaemia. Beta-thalassaemia is caused by deficient production of β-globin. The new treatment, marketed by Bluebird Bio Inc. under the name of Zynteglo, is based on the insertion of a functional β-globin gene in the patients’ own blood stem cells and may therefore provide the patient with functional β-globin for a lifetime. The treatment has proven safe and efficient in long-running clinical trials.


Universal, but not for all 

Any transfusion-dependent β-thalassemia patient over the age of 12 and without a compatible donor would be eligible for treatment pending its final approval by the European Commission later in the year. However, as with any new medical development, patients for whom alternative treatments are currently failing may eagerly welcome this new treatment option, while those with good disease management may want to wait until gene therapy for thalassaemia has become more affordable. And potentially still more efficient and safer.



It is difficult for companies to create profits with one-off curative treatments, such as Zynteglo. Moreover, all gene therapy treatments are quite costly, because of high development and production costs. There is still no official price tag for Zynteglo, but the conceptually similar treatment Strimvelis for the immunodeficiency ADA-SCID costs over €500,000 per treatment. Still, thalassemia patients are far more numerous than ADA-SCID patients, and Zynteglo may also be suitable for millions of patients with the related sickle cell disease, which may result in much lower pricing for Zynteglo long-term. Because of the high lifetime cost of disease management, some health systems may spend public money on curative treatments such as Zynteglo. Particularly for low - and middle - income countries, however, it may turn out that the new curative treatment will be reserved for those few who can afford to pay for it out of their own pockets.


Efficiency versus Safety

Current limitations in the delivery technology mean that the therapeutic gene is inferior to its natural equivalent. This creates a dilemma. On the one hand, the severest forms of β-thalassemia may stay transfusion-dependent or may only be turned into transfusion-independent, milder forms of the disease at low gene doses. On the other hand, a higher gene dosage would be more efficient but would also increase the risk of adverse events, such as leukemia. 


Future alternatives

Other products similar to Zynteglo may prove more efficient, but are at earlier stages of development. Meanwhile, new treatments, such as those based on genome editing instead of gene addition, may have higher medical efficacy and inherently lower risk for the patients. However, those treatments are only now entering clinical trials and are still years away from assessment for approval by regulatory authorities.


A shift in perspective

Is it tenable to abort a thalassemic pregnancy if curative treatments are available? For most societies, disease prevention will remain critical to keeping disease management or expensive curative treatments affordable. At the same time the prospect of Zynteglo and of other upcoming cures is already changing the attitudes of thalassemic patients and of couples with at-risk pregnancies. This will give rise to an essential debate of principles. Zynteglo will not be the final word in gene therapy for β-thalassaemia, but it contributes to a new sense of empowerment and of perspective for thalassaemic patients, and that in itself is already quite ‘therapeutic’. 

This article was written by:

Carsten Werner Lederer, PhD
TIF Expert Advisor
Laboratory Scientific Officer & Assistant Professor 
Molecular Genetics Thalassaemia Department
The Cyprus Institute of Neurology and Genetics & The Cyprus School of Molecular Medicine

For more information:
Thalassaemia International Federation
PO Box 28807, 2083 Strovolos, Cyprus
Tel: +357 22 319 129
Fax: +357 22 314 552