bluebird bio announced new data from patients in Group C of its ongoing Phase I/II HGB-206 study of LentiGlobin for sickle cell disease (SCD) at the 24th European Hematology Association (EHA) Congress

bluebird bio announced new data from patients in Group C of its ongoing Phase I/II HGB-206 study of the company’s investigational LentiGlobin gene therapy for sickle cell disease (SCD) at the 24th European Hematology Association (EHA) Congress.

“The latest Group C data from our ongoing Phase I/II study show robust production of gene therapy-derived anti-sickling hemoglobin, HbAT87Q, such that patients with six or more months of follow-up after treatment with LentiGlobin for sickle cell disease had median sickle hemoglobin levels reduced to 50 percent or less of total hemoglobin, in the absence of blood transfusions. The potential for gene therapy with LentiGlobin to fundamentally alter the pathophysiology of sickle cell disease was also supported by the normalization of hemolysis markers, increase in total hemoglobin and substantial reduction in vaso-occlusive crises relative to baseline,” said David Davidson, M.D., chief medical officer, bluebird bio. “Further insight into these encouraging clinical results was provided by findings from an exploratory assay used to evaluate the expression of HbAT87Q, which demonstrated 70 percent or more of patient red blood cells contain HbAT87Q at nine months after treatment.”

Phase 1/II: HGB-206 : HGB-206 is an ongoing, Phase 1/II open-label study designed to evaluate the efficacy and safety of LentiGlobin gene therapy for SCD that includes three treatment cohorts: Groups A, B and C. As of March 7, 2019, 25 patients were enrolled and a total of 13 patients had been treated with LentiGlobin in Group C, with a median post-treatment follow-up of nine months (1.0 – 15.2 months). “The severity of sickle cell disease is not always recognized, and many people are unaware that individuals are debilitated by the effects of sickle cell disease,” said Julie Kanter, M.D., University of Alabama at Birmingham, Birmingham, Ala. “Group C of the Phase 1/II HGB-206 study of LentiGlobin now includes multiple patients with at least one year of follow-up, and in these individuals, many with a history of vaso-occlusive crises, their symptoms appear to be resolving. There have been no incidents of acute chest syndrome or serious vaso-occlusive crises reported, and many of their labs are approaching normal.”

Eight of the 13 treated patients in Group C had at least six months of follow-up at the time of the data cutoff. In these patients, production of gene therapy-derived hemoglobin (HbAT87Q) ranged from 4.5–8.8 g/dL and total unsupported hemoglobin (Hb) levels ranged from 10.2–15.0 g/dL at the last study visit. The median concentration of HbAT87Q continued to increase, accounting for greater than 50 percent of total Hb in patients with at least 12 months of follow up (n=4). No ACS or serious vaso-occlusive crisis (VOC) was reported in patients in Group C at up to 15 months post-treatment with LentiGlobin. In an exploratory analysis, key markers of hemolysis, including reticulocyte counts, lactate dehydrogenase (LDH) and total bilirubin concentration, trended toward normal levels. As of the data cutoff date, the safety data from all patients in HGB-206 are reflective of underlying SCD, the known side effects of hematopoietic stem cell (HSC) collection and myeloablative conditioning. There have been no serious adverse events (SAEs) related to LentiGlobin for SCD. One mild, non-serious event of hot flush was reported that the investigator considered to be related to LentiGlobin for SCD; it occurred and resolved on the day of drug product infusion and did not require treatment.

Established tools, including high-performance liquid chromatography (HPLC), are used to measure the amount of HbAT87Q in a blood sample. In order to detect HbAT87Q and HbS protein expression at a cellular level, bluebird bio has utilized a new, exploratory assay to demonstrate the pancellular expression of HbAT87Q in patients treated with LentiGlobin. The assay enables detection of HbAT87Q and HbS protein expression at a cellular level. Results from this assay showed that in samples from five patients who were at least nine months post-treatment, on average, at least 70 percent of each patient’s RBCs expressed HbAT87Q.