- Bluebird Bio, a Cambridge, MA-based gene therapy company, unveiled new details on improvements to production processes for its LentiGlobin drug product, giving greater clarity into its regulatory plans in presentations to investors during its first R&D day held last week.
- The biotech claimed its new manufacturing process increased the average number of cells which contained corrected genes by between two and three times compared to initial methods. Bluebird hopes this will make its LentiGlobin product more effective in treating the blood disorders ß-thalassemia and sickle-cell disease.
- Investors shrugged off Bluebird's optimism, however, pushing Bluebird's stock down by over 13% Friday. The sell-off reversed steady gains over the past month, which had bid up the stock's price ahead of the "Gene Therapy" day.
Bluebird said it has successfully scaled up its clinical manufacturing under the new "process 2." All three of its LentiGlobin trials — HGB-207 and HGB-212 in ß-thalassemia and HGB-206 in sickle-cell — will now use the improved process for inserting the targeted gene sequences into patient hematopoietic stem cells ex-vivo.
Under the new method, two unspecified "enhancers" have been added to the transduction (transfer of DNA) step of the process. This has boosted the percentage of cells successfully transduced, increasing the vector copy number in the LentiGlobin drug product, according to a head-to-head in vitro comparison BlueBird conducted between the two methods (see chart).
Another comparison among sickle cell subject retains, or cells that were not newly extracted, showed a similar effect, albeit among fewer patient samples.
Bluebird Bio already opened enrollment into its HGB-207 Phase 3 trial under the new process back in September, aiming for transfusion independence among ß-thalassemia patients.
During the presentation last week, Bluebird also gave more details on the structure of its ß-thalassemia and sickle-cell studies, as well as outlining its regulatory plans moving forward.
HGB-207 will enroll two cohorts of patients with non-ß0/ß0 thalassemia — 15 adults and adolescents in one group and 8 pediatric patients in another. HGB-212, on the other hand, will enroll 15 patients of all ages with the ß0/ß0 genotype. That trial is expected to begin in 2017.
Previously, Bluebird had planned two 15-patient studies, each conducted across all genotypes but split based on age.
"We've reached general agreement with the Food and Drug Administration that we could file a biological license application or BLA for patient with transfusion dependent ß-thalassemia with a non-ß0/ß0 genotype based on HGB-207. This filing will be first made in adults and adolescence and then we intend to expand the indication based on the second cohort of HGB-207 for pediatric patients," said Anne-Virginie Eggimann, VP of regulatory science at Bluebird, speaking during the presentation last week.
No clinical data from testing done under the new process will be available at the upcoming meeting of the American Society of Hematology. But Bluebird CEO Nick Leschly emphasized that the next 18 months will be critical, both for LentiGlobin in ß-thalassemia and for its Lenti-D product in cerebral adrenoleukodystrophy.