Presentations at EHA highlight gene therapy approaches to beta-thalassemia, sickle cell disease


Two completely different gene therapy approaches to treating two blood problems have been the topic of displays at a hematology assembly Friday, with each exhibiting efficacy.

Cambridge, Massachusetts-based bluebird bio stated that knowledge from its Phase III examine of Zynteglo (betibeglogene autotemcel) – also referred to as LentiGlobin – in transfusion-dependent beta-thalassemia (TDT) introduced at the European Hematology Association’s digital annual convention confirmed {that a} majority of sufferers achieved transfusion independence and maintained near-normal hemoglobin ranges. Meanwhile, Boston-based Vertex Pharmaceuticals and Zug, Switzerland-based accomplice CRISPR Therapeutics introduced the presentation of early knowledge from their Phase I/II examine of CTX001, a CRISPR/Cas9-based gene therapy, in TDT, in addition to knowledge from a examine of the identical therapy in sickle cell disease.

Shares of bluebird have been up 2.6% on the Nasdaq in Friday afternoon buying and selling, whereas shares of Vertex and CRISPR have been respectively up 1% and down 1.5%. Zynteglo, which has a conditional advertising and marketing authorization for sure TDT sufferers in Europe, features by including a purposeful copy of a modified beta-globin gene into sufferers’ hematopoietic stem cells, permitting them to produce hemoglobin at ranges that cut back or remove the necessity for transfusions. CTX001 is an ex-vivo gene-edited therapy by which sufferers’ personal hematopoietic stem cells are engineered to produce excessive ranges of fetal hemoglobin – the oxygen-carrying hemoglobin naturally current at beginning and that switches to the grownup type of hemoglobin – in crimson blood cells.

Data from two of bluebird’s research – HGB-207, which enrolls sufferers who wouldn’t have the beta-0/beta-Zero genotype; and HGB-212, enrolling sufferers who’ve that and different genotypes – have been introduced at EHA. Serious adversarial occasions between the research included veno-occlusive liver disease, low blood counts and fever, although no deaths have been reported in both Phase III examine.

Among the 23 sufferers enrolled in HGB-207, 19 have been evaluable for efficacy, with 89% of these attaining transfusion independence after a median 19.Four months’ follow-up. Median weighted common whole hemoglobin ranges reached 11.9 grams per deciliter of blood. Previously, these sufferers had required a median 17.5 blood transfusions per 12 months. Patients with beta-thalassemia require routine blood transfusions to preserve hemoglobin ranges above 9.5 grams per decilieter.

In HGB-212, eight of the 15 sufferers handled have been evaluable for efficacy, with six of these attaining transfusion independence, which that they had maintained for a median 13.6 months. Among 13 sufferers with at least seven months of follow-up, 85% had not acquired a transfusion in additional than seven months, regardless of having beforehand required a median 18.5 transfusions per 12 months.

Meanwhile, Vertex and CRISPR introduced knowledge for 2 sufferers with TDT from their examine of CTX001. The first affected person had 15 months of follow-up after infusion and had change into transfusion-independent, with whole hemoglobin ranges of 14.2 grams per deciliter and fetal hemoglobin of 13.5 grans per deciliter. Moreover, the affected person had a 100% stage of crimson blood cells expressing fetal hemoglobin, whereas allelic enhancing within the bone marrow was at 78.1% after six months and 76.1% at one 12 months. That affected person had required 34 transfusions per 12 months.

While the allelic enhancing determine had fallen by two proportion factors between the six- and 12-month marks, the corporate stated in an emailed assertion that the share distinction was not significant and that it was “encouraging” that the quantity remained better than 75%.

The second affected person had required 61 transfusions per 12 months. Five months after infusion, the affected person had change into transfusion-independent, with whole hemoglobin at 12.5 grams per deciliter, fetal hemoglobin at 12.2 grams per deciliter and fetal hemoglobin-expressing crimson blood cells at 99.4%.

Data from the primary affected person within the sickle cell disease examine consisted of a follow-up from knowledge introduced in November 2019, exhibiting that 9 months after infusion, the affected person had change into transfusion-independent and freed from the veno-occlusive crises related to the disease. Total hemoglobin ranges have been 11.eight grams per deciliter, with 46.1% fetal hemoglobin, 99.7% fetal hemoglobin-expressing crimson blood cells and bone marrow allelic enhancing at 81.4% after six months.