Very small beta-thalassemia gene therapy trial gets investors' blood up

Two patients with the serious inherited blood disorder beta-thalassemia have been able to stop blood transfusions 12 days after receiving experimental gene therapy.

The LentiGlobin treatment, developed by Bluebird bio, builds on a previous prototype which allowed one patient to stop receiving blood transfusions after 12 months.

This positive clinical data, presented at the 19th Annual Congress of the European Hematology Association in Milan, Italy, offers hope to the 288,000 patients with beta-thalassemia worldwide.

'Thalessemia major patients are very sick', explains Professor Marina Cavazzana-Calvo of the Necker-Enfants Malades Hospital, Paris, who was the principle investigator of the study. 'They have to receive transfusions regularly for all of their life. Because of this huge number of transfusions they suffer from a huge iron overload. To set up a treatment that can make them free of any transfusion treatment should be a great step toward curative treatment'.

Beta-thalassemia is caused by a missing or defective gene which prevents oxygen-carrying hemoglobin from functioning properly. Bluebird’s LentiGlobin treats the disease by inserting a fully functional human beta-globin gene into the patient’s blood-forming hematopoietic stem cells using a modified HIV virus, often referred to as a lentivirus.

In 2010 a beta-thalassemia patient treated with a previous version of the therapy was able to go without blood transfusions for six years (reported in BioNews 576). However, in this instance the patient still required transfusions for 12 months after receiving the therapy. Since then, Bluebird, whose aim is to develop gene therapy products to treat patients with severe genetic and orphan diseases, has improved both the ability of the virus to insert the corrected gene and the process by which hematopoietic stem cells are extracted, and it is these improvements which are responsible for the positive clinical findings.

'Following the [gene] transplant, we're seeing near normal levels of hemoglobin,' said Bluebird's chief medical officer David Davidson. 'These early results far exceeded our expectations'.

Bluebird's shares jumped 70 percent on the interim results from the phase I/II study. The surprisingly strong findings have excited investors and fuelled hope that Bluebird could file with the US Food and Drug Administration sooner than expected.