Outcomes for Initial Patient Cohorts with up to 33 Months of Follow-up in the Hgb-206 Phase 1 Trial

BackgroundSickle cell disease (SCD) is a progressively debilitating genetic disease causing significant morbidity and early mortality for which a universal curative therapy is lacking. Expression of an anti-sickling β-globin via gene transfer into hematopoietic stem cells (HSCs) may reduce or eliminate SCD symptoms. LentiGlobin Drug Product (DP) contains autologous CD34+ cells transduced with the BB305 lentiviral vector (LVV) encoding β-globin with an anti-sickling substitution (T87Q). The safety and efficacy of LentiGlobin in adults with severe SCD is being evaluated in the ongoing multi-center Phase 1 study HGB-206 (NCT02140554). The first 7 patients (Group A) received DP from bone marrow harvested (BMH) HSCs and demonstrated stable but sub-optimal gene therapy-derived hemoglobin (HbAT87Q). The protocol was amended to include pre-harvest transfusions, increased target busulfan levels and a refined DP manufacturing process (Group B). The study is now enrolling patients in Group C, treated under modified protocol and including DP manufactured from plerixafor-mobilized HSCs. Data from patients in fully enrolled Groups A and B are shown here.MethodsPatients ≥18 years old with severe SCD, as previously described, were enrolled. CD34+ cells from BMH were transduced with the BB305 LVV to produce LentiGlobin DP. Following myeloablative busulfan conditioning, patients were infused with DP. Group A patients received DP from the original manufacturing process. One Group B...

Source: Blood - November 21, 2018 Category: Hematology Authors: Kanter, J., Tisdale, J. F., Kwiatkowski, J. L., Krishnamurti, L., Mapara, M. Y., Schmidt, M., Miller, A. L., Pierciey, F. J., Shi, W., Ribeil, J.-A., Walters, M. C., Thompson, A. A. Tags: 114. Hemoglobinopathies, Excluding Thalassemia-Clinical: Poster I Source Type: research