Gene therapy exceeds expectations in β-thalassemia
In HGB-205, there were no AEs considered possibly or probably related to LentiGlobin.
The 3 serious AEs were tooth infection and major depression (both grade 3), as well as pneumonia (grade 2).
Efficacy
The median time to neutrophil engraftment was 18.5 days (range, 14.0 to 30.0) in HGB-204 and 16.5 days (range, 14.0 to 29.0) in HGB-205.
The median time to platelet engraftment was 39.5 days (range, 19.0 to 191.0) in HGB-204 and 23.0 days (range, 20.0 to 26.0) in HGB-205.
In both studies, the median follow-up was 26 months (range, 15 to 42) after LentiGlobin infusion.
At last follow-up, all but 1 of the 13 patients with a non-β0/β0 genotype had stopped receiving RBC transfusions.
At the last study visit (12 to 36 months post-treatment), the median HbAT87Q level in these patients was 6.0 g/dL (range, 3.4 to 10.0), and the median total hemoglobin was 11.2 g/dL (range, 8.2 to 13.7).
In the 8 patients with a β0/β0 genotype and the 1 patient with 2 copies of the IVS1-110 mutation, the median annualized transfusion volume decreased by 73% after LentiGlobin infusion.
Two patients with a β0/β0 genotype were able to stop receiving RBC transfusions, as was the patient with 2 copies of the IVS1-110 mutation.
At their most recent study visit (12 months to 30 months), these 3 patients had median HbAT87Q levels of 8.2 g/dL, 6.8 g/dL, and 6.6 g/dL, respectively. Their median total hemoglobin levels were 9.0 g/dL, 10.2 g/dL, and 8.3 g/dL, respectively.
For the 6 patients with a β0/β0 genotype who continued to receive RBC transfusions, the median HbAT87Q level was 4.2 g/dL (range, 0.3 to 8.7) at the last study visit.
“There is room for improvement, as we’d like to see the elimination of dependency on transfusion even for patients with the most severe form of the disease,” said study author Philippe Leboulch, MD, of Brigham and Women’s Hospital in Boston, Massachusetts.
“But there is also hope with protocol modifications we have introduced in our phase 3 trials.”
