A gene therapy trial for transfusion-dependent thalassaemia, an inherited blood disorder, gave positive results in an interim analysis, with the majority of patients being transfusion-free following treatment.
The two Phase I/II trials enrolled a total of 22 patients, 15 of whom achieved transfusion-free status, while the remaining number required less frequent transfusions.
"Reducing or stopping transfusions is important for patients with thalassaemia because they are a double-edged sword—essential for survival but also responsible for life-changing, life-shortening side-effects,” University of Oxford professor of paediatric haematology Irene Roberts said.
The gene therapy—known as LentiGlobin—was developed by Massachusetts-based company Bluebird Bio. It works through genetically correcting cells and transplanting them back into the patient’s body. Using a modified virus, the defective gene in participants’ blood stem cells were altered in the lab before being reinfused in patients to try and stimulate red blood cell production.
Prior to the infusion, subjects first had to undergo chemotherapy to remove all blood stem cells with defective genes from their bodies. Participants were monitored for 15 to 42 months after receiving the new cells.
The study found patients typically reached peak haemoglobin production at nine to 12 months following infusion. Treatment-related adverse events seen were typical of autologous stem cell transplantation, and no safety issues were attributed to the gene therapy in either study.
"We saw remarkable outcomes using LentiGlobin gene therapy, with most patients no longer needing monthly transfusions,” lead author Dr Alexis Thompson said.
“These study results exceeded our expectations with clinical benefit for nearly all patients, and suggest that gene therapy may be an effective treatment for thalassaemia in the future.”
The researchers warn that the longer term effects are not yet known, and participants are due to be monitored for a further 15 years. Others have voiced concerns over the expense of the treatment, questioning whether it would be possible to administer it in developing countries, where the majority of cases occurs. Despite these uncertainties, Bluebird Bio has stated its plans to seek approval for its treatment in Europe by the end of this year.
A new Phase III trial is due to start, examining the treatment in younger patients.
“While these gene therapy trials were the largest for thalassaemia to date, we need to evaluate effectiveness in a much larger population,” said Thompson.
“Since we saw such positive results, we are now enrolling patients as young as 5 years old on a Phase III trial of gene therapy for transfusion-dependent thalassaemia.”
Results from the study were published in the New England Journal of Medicine.
Thalassaemia impairs patients’ ability to produce enough haemoglobin in their red blood cells, which in turn hinders oxygen reaching all parts of the body. Symptoms typically include anaemia, tiredness and shortness of breath. In extreme cases patients require red blood cell transfusions every month in order to survive, though this can lead to serious complications due to iron toxicity and viral infections.
Globally, roughly 300,000 people suffer from beta-thalassaemia, making the condition one of the most common genetic disorders. The majority of cases occur in Mediterranean countries, the Middle East, Asia, India, and parts of Africa and South America. In the US, around 10,000 to 15,000 patients have beta-thalassaemia.