bluebird bio today disclosed its first data, including some promising results, from a pair of clinical studies assessing its LentiGlobin™ gene therapy candidate—including a Phase III study that followed a change in its manufacturing process.
In the Phase III Northstar-2 (HGB-207) study of LentiGlobin in patients with transfusion-dependent β-thalassemia (TDT) and non-β0/β0 genotypes, early interim data showed that the first 3 of 15 patients treated to date achieved higher drug product vector copy number (DP VCN) and lentiviral vector positive (LVV+) cell production than in the earlier Northstar (HGB-204) study, bluebird said.
Those results are correlated with higher production of hemoglobin A (HbA)T87Q and ultimately may address known patient-to-patient variability, bluebird bio CMO David Davidson, M.D., said in a statement.
“The first patient treated in this study exemplifies the promise of gene therapy: discontinuing blood transfusions approximately a month after treatment and achieving a normal level of total hemoglobin production at six months post-treatment,” Dr. Davidson stated.
According to bluebird, the first patient achieved normal total hemoglobin (13.3 g/dL) after discontinuing transfusions; producing 9.5 g/dl of HbAT87Q at last follow-up.
bluebird cautioned that the data was early, and that not all three patients enjoyed results as positive as the first patient. The second patient showed a lower percentage of LVV+ cells (53%) than either patients 1 (77%) or 3 (77% and 82%). However, neither patients 2 or 3 had sufficient follow-up to record clinically relevant data for total hemoglobin or days since last transfusion.
Northstar-2 is an ongoing, open-label, single-dose, international, multicenter study designed to evaluate the safety and efficacy of LentiGlobin drug product for the treatment of patients with TDT and non-β0/β0 genotypes. As of June 2, the drug product had been manufactured for six patients. The median DP VCN for these patients was 3.0 (range: 2.4–4.0), compared to a median DP VCN of 0.7 (range: 0.3–1.5) in Northstar.
“Although early, these data add to the growing body of clinical evidence that indicate that LentiGlobin may offer a transformative benefit for patients with TDT,” added Alexis Thompson, MD, of Ann & Robert H. Lurie Children’s Hospital of Chicago, a primary investigator on the study.
The Phase III study followed what the company said was an improvement in the manufacturing process by which the patient’s cells are transduced with the LentiGlobin viral vector, a change aimed at increasing vector copy number and the percentage of cells successfully transduced.
bluebird bio also announced results from its Phase I/II HGB-205 study, designed to assess LentiGlobin in patients with TDT and severe sickle cell disease (SCD). Those results, according to the company, showed the potential for durable treatment effect of LentiGlobin, with stable HbAT87Q production through 3.5 years of follow-up and sustained clinical benefit.
The company cited data from four TDT patients, all of whom remained free of transfusions since shortly after receiving LentiGlobin. At the last study visit, one patient had been free of transfusions for 41.9 months, compared with 38.7 months, 20.3 months, and 20.4 months for the other three patients—the last of which was also homozygous for the severe β+ mutation IVS1-110.
In the three patients with SCD, the patient with the best results was producing 50% HbAT87Q , well above the approximately 30% anti-sickling hemoglobin level predicted to have potential clinical impact on the disease, at last follow-up 31.7 months following treatment.
The other two SCD patients showed levels of 20% and 15% at last follow-up (6.1 months and 3.4 months after treatment, respectively.)
HGB-205 is an ongoing, open-label, single-center study in which four patients with TDT, and three with severe SCD, have undergone infusion with LentiGlobin drug product as of June 2.
“We are beginning to see evidence of the long-term durability of benefit from treatment with LentiGlobin, with some TDT patients even transitioning off of chelation therapy,” said the HGB-205 study’s primary investigator, Marina Cavazzana, M.D., Ph.D., a professor of medicine at Paris Descartes University, research director at the Centre for Clinical Research in Biotherapy, Necker Hospital, and at the Imagine Institute of Genetic Diseases in Paris.