Gene Therapy Looks Promising for Transfusion-Dependent β-Thalassemia

Transfusion-dependent β-thalassemia is a severe genetic disease characterized by reduced or absent hemoglobin levels
Transfusion-dependent β-thalassemia is a severe genetic disease characterized by reduced or absent hemoglobin levels

A majority of patients with transfusion-dependent β-thalassemia (TDT) were able to achieve freedom from chronic blood transfusion after receiving the gene therapy LentiGlobin (autologous CD34+ cells transduced with the BB305 vector; bluebird bio, Inc.), according to data from two Phase 1/2 studies. Findings from these studies were published in the New England Journal of Medicine.

The safety and efficacy of LentiGlobin were evaluated in 2 independent 2-year clinical studies: HGB-204 (Northstar, N=18), an open-label, single-dose, nonrandomized, multicenter Phase 1/2 study in patients with TDT, and HGB-205 (N=4), an ongoing open-label, single-dose, nonrandomized, single-center Phase 1/2 study in patients with TDT and severe sickle cell disease. 

Interim results from both studies showed that one-time treatment with LentiGlobin gene therapy eliminated the need for transfusions for most of the 22 patients who were followed for ≥2 years. Specifically, 12 of 13 patients with a non-β00 genotype stopped receiving regular red blood cell transfusions (median time since last transfusion: 27 months). Nine patients with β00 or IVS1-110/IVS1-110 genotype (functional adult hemoglobin production nearly or completely eliminated) had a 73% decrease in median transfusion volume, of which 3 patients stopped receiving regular red blood cell transfusions; the 6 remaining patients continued to receive transfusions with all but one having clinically meaningful reductions in the number and volume of transfusions. 

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By 36 months post-treatment, the degree of hemolysis was fully corrected in 2 of 4 patients with TDT who stopped receiving transfusions after LentiGlobin therapy in HGB-205. Moreover, 3 patients with non-β00 genotypes transitioned to therapeutic phlebotomy to decrease iron overload accumulated from previous chronic transfusions

“Nearly all patients in the two studies with a non-β00 genotype achieved freedom from chronic blood transfusions and, importantly, several of these patients reached normal or near-normal total hemoglobin levels and sustained those levels throughout the interim study period," stated Dave Davidson, MD, CMO of bluebird bio. 

According to the Company, the safety characteristics of LentiGlobin appear consistent with myeloablative conditioning with busulfan. In the Northstar study, there were 5 mild adverse events and 9 serious adverse events reported (including veno-occlusive liver disease), however none were considered to be treatment-related; in HGB-205, 3 serious adverse events were reported. 

For more information visit NEJM.org.