Bluebird's gene therapy 2.0 weans beta-thalassemia patients off blood transfusions

Nick Leschly, CEO of Bluebird Bio

Gene therapy 2.0 at bluebird bio is demonstrating some early signs of success with an upgrade to its experimental therapy for the genetic blood disorder beta-thalassemia demonstrating promising results in a pair of patients, weaning them off the regular blood transfusions needed to stay alive.

Cambridge, MA-based Bluebird ($BLUE) has been testing an improved lentiviral vector needed to get a corrective beta-globin gene in place to repair their ability to produce hemoglobin in a study of LentiGlobin BB305. One of those subjects produced 6.6 g/dL of therapeutic betaAT87Q-globin at 4.5 months as a result of the therapy and another hit 4.2 g/dL of betaAT87Q-globin at two months--enough to prevent the need for further monthly transfusions and symptoms like severe anemia and splenomegaly, at least for now.

The data were cheered on by investors Monday morning as the biotech's volatile stock rocketed up more than 50% in premarket trading.

Bluebird has been tinkering with its lentiviral tech to come up with a new-and-improved therapy that can be easier to produce and more effective for patients. Their presentation this weekend at a scientific conference in Milan suggests that their work is paying off as hoped for, and bluebird CEO Nick Leschly tells FierceBiotech that the results provide a positive sign that the new tech can be more widely used in its other pipeline projects.

"If you step back," says Leschly, "one of the big questions is how do you do gene therapy in an industrial fashion, one that is scalable and reproducible." And this new product "well exceeded our expectations."

Gene therapy work has been going on in the clinic for decades now, but a string of biotechs like bluebird feel that they've managed to overcome the flaws that destroyed so many earlier efforts. And in small studies like these, they've been presenting key proof-of-concept data for a new wave of treatments pointed to future registration trials. In bluebird's case, stem cells are extracted from patient and then treated with the lentivirus before being reinjected into the patient, with the correcting gene sequence inserted into the chromosome.

Success for this approach on beta-thalassemia could be defined as fewer transfusions, says Leschly. "If we can get near transfusion independent, that would be spectacular." Even better would be a "one-time, transformative treatment" that could provide a cure for these patients. The biotech is also looking for, and seeing, a much faster rate of response.

Put in context, adds Dave Davidson, the chief medical officer in bluebird and a veteran of Genzyme, the earlier version of this therapy took a year to generate enough hemoglobin in one of the patients. Now investigators are counting the initial response in a matter of days.

For the two subjects treated in bluebird's study using the earlier version lentiviral HPV569 product, one still no longer requires blood transfusions after 72 months. The two are producing 2.7 g/dL and 0.4 g/dL of therapeutic betaA-T87Q-globin post-transplant, respectively.

In this particular early-stage study bluebird has now recruited four of the 7 patients it needs, while investigators are also at work scouting for 15 patients needed for a sister study.

Bluebird, a 2012 Fierce 15 company, was one of a group of star biotechs to put together successful IPOs last year. Initially backed by Third Rock and Genzyme, the team reorganized and renamed Genetix back in 2010 and went on to strike a CAR-T development deal with Celgene ($CELG). The lead program at bluebird is focused on childhood cerebral ALD while investigators are also pursuing another program for LentiGlobin in sickle cell disease as well. 

- here's the release

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