EFFICACY
Help them let go of chronic transfusions1
TRANSFUSION INDEPENDENCE
The majority of patients* treated with ZYNTEGLO achieved transfusion independence1
Transfusion independence was defined as a weighted average Hb of ≥9 g/dL without any transfusions for a continuous period of ≥12 months at any time during the study after infusion of ZYNTEGLO.1
*Defined as patients who have completed the parent study and achieved transfusion independence or will not achieve transfusion independence in the parent study.1

All patients who achieved transfusion independence maintained transfusion independence.1

PHASE 1/2 - COMPLETED1
(HGB-204, HGB-205)
(Primary endpoint: transfusion independence by Month 24)
Data beyond 24 months are from the LTF-303 study.

PHASE 3 - ONGOING1
(HGB-207)
(Primary endpoint: transfusion independence by Month 24)
As the Phase 3 trial is ongoing, data shown here are for the patients who were evaluable for transfusion independence.
These data are from the HGB-207 study only.
All patients who achieved transfusion independence maintained it at last follow-up1
- Follow-up in the ongoing Phase 3 trials is up to 26.3 months (min, max: 5.6, 26.3)1
- Follow-up in the Phase 1/2 trials and LTF-303 is up to 61.3 months (min, max: 35.8, 61.3)1

Median total Hb over time in non-β0/β0 TDT patients treated with ZYNTEGLO who have achieved transfusion independence1

The graph only includes patients who have not received a transfusion in 60 days. Bars represent interquartile range. Includes data from LTF-303.
The Phase 3 trials are conducted with improved transduction compared to the Phase 1/2 studies, resulting in an increased average number of functional copies of the βA-T87Q-globin gene integrated into autologous cells1
TOTAL Hb DURING TRANSFUSION INDEPENDENCE
Patients treated with ZYNTEGLO achieved Hb† levels that enabled transfusion independence1

Median Hb levels in patients with non-β0/β0 TDT achieving transfusion independence1‡

HGB-204 + HGB-205
(n=11)
(n=11)
Phase 1/2 - COMPLETED1

HGB-207
(n=9)
(n=9)
Phase 3 - ONGOING1
†Weighted average Hb.1
‡Transfusion independence was defined as a weighted average Hb of ≥9 g/dL without any transfusions for a continuous period of ≥12 months at any time during the study after infusion of ZYNTEGLO.1
Hb AT 6 MONTHS
ZYNTEGLO-derived Hb (HbAT87Q) supported total Hb in all patients at 6 months who did not receive a transfusion for the prior 60 days10
In the ongoing Phase 3 trial HGB-207, median total Hb at 6 months for patients who did not receive a transfusion for the prior 60 days was 11.8 g/dL, primarily driven by HbAT87Q1
MEDIAN HbAT87Q AT 6 MONTHS1
MEDIAN TOTAL Hb
AT 6 MONTHS*1
MEDIAN TOTAL Hb AT 6 MONTHS*1
MEDIAN TOTAL Hb
AT 6 MONTHS*1

The Phase 3 trials are conducted with improved transduction compared to the Phase 1/2 studies, resulting in an increased average number of functional copies of the βA-T87Q-globin gene integrated into autologous CD34+ cells.1
*Patients who have not received transfusions in the prior 60 days
Phase 1/2 studies, median HbAT87Q
HGB-204 (n=10):1
4.2 g/dL (min, max: 1.0, 8.5)
HGB-205 (n=4):1
7.5 g/dL (min, max: 4.9, 9.6)
Phase 1/2 studies, median total Hb
HGB-204 (n=7):1
9.2 g/dL (min, max: 7.7, 13.3)
HGB-205 (n=4):1
10.7 g/dL (min, max: 7.6, 13.4)
Phase 1/2 studies, median HbAT87Q
HGB-204 (n=10):1
4.2 g/dL (min, max: 1.0, 8.5)
HGB-205 (n=4):1
7.5 g/dL (min, max: 4.9, 9.6)
Phase 1/2 studies, median total Hb
HGB-204 (n=7):1
9.2 g/dL (min, max: 7.7, 13.3)
HGB-205 (n=4):1
10.7 g/dL (min, max: 7.6, 13.4)
ZYNTEGLO enables the production of functional gene therapy–derived HbA (HbAT87Q) that can be quantified by bluebird bio over time.1
REDUCED IRON OVERLOAD
Reduced iron overload was shown at 48 months for patients in HGB-204 and HGB-205 who achieved transfusion independence1

Serum ferritin and liver iron content (LIC) in patients who achieved transfusion independence1
(n=5, HGB-204; n=2, HGB-205)

MEDIAN CHANGE FROM BASELINE IN SERUM FERRITIN1

MEDIAN CHANGE FROM BASELINE IN LIC1
- After Zynteglo infusion, patient iron chelation was managed at physician discretion.1
- Of the 14 non-β0/β0 patients treated in HGB-204 and HGB-205 that completed Month 6, 9 patients (64.3%) reported ongoing chelation use at last follow-up.
- The remaining 5 patients (35.7%) had stopped iron chelation, of whom 4 patients (28.6%) have stopped chelation for at least 6 months with median (min, max) time from stopping chelation to last follow-up of 26.40 (11.5, 42.2) months for these 4 patients.
- Of the 14 treated patients, 3 patients in HGB-205 (21.4%) received phlebotomy to remove iron.
- For the 11 patients that achieved TI, 4 patients (36.4%) stopped chelation for at least 6 months and 3 patients (27.3%) received phlebotomy
*Baseline values are pooled for all trials for both serum ferritin and liver iron content: HGB-204, N=10; HGB-205, N=4; HGB-207, N=15; HGB-212, N=3.
Erythropoiesis: ZYNTEGLO increases myeloid/erythroid ratios1
In an exploratory analysis from the Phase 3 studies, bone marrow biopsies taken before ZYNTEGLO infusion showed low myeloid/erythroid ratios (n=15, HGB-207; n=3, HGB-212), reflective of erythroid hyperplasia and consistent with a diagnosis of TDT1

Baseline and 12-month myeloid/erythroid ratios (n=9)1*

BASELINE MYELOID/ERYTHROID RATIO


~12 MONTHS AFTER ZYNTEGLO MYELOID/ERYTHROID RATIO
*Patients who had sufficient on-study follow-up to achieve TI and obtain a 12-month bone marrow assessment.1
†For 9 patients who achieved TI and had a Month 12 bone marrow assessment, median myeloid/erythroid ratios increased from 0.2 at baseline to 0.8 at Month 12 after ZYNTEGLO infusion.1 The remaining patient did not have an increase in myeloid/erythroid ratio.10
ZYNTEGLO was evaluated in four clinical trials and a long-term follow-up study1,7
-
45 patients were part of the safety assessments of ZYNTEGLO (≥12 years of age with TDT)1
-
32 patients were assessed for efficacy (≥12 years of age with non-β0/β0 TDT)1
In the Phase 1/2 and 3 trials, patients had a history of RBC transfusions of ≥100 ml/kg/year or ≥8 transfusions per year in the 2 years prior to enrolment.
Median duration of follow-up data is presented as pooled for the Phase 1/2 and Phase 3 trials in the Summary of Product Characteristics.
*HGB-204 and HGB 205 were Phase 1/2 open-label, single-arm 24-month studies that included 22 patients with TDT treated with ZYNTEGLO (N=18, HGB-204; N=4, HGB-205), of whom 14 had a non-β0/β0 genotype (N=10, HGB-204, N=4, HGB-205) and 8 had a β0/β0-genotype in HGB-204. All patients completed HGB-204 and HGB-205 and enrolled for long-term follow-up in the LTF-303 study.1
†Transfusion independence is defined as weighted average haemoglobin ≥ 9 g/dL without any RBC transfusions for ≥ 12 months at any time during the study after infusion.1
‡Transfusion reduction defined as ≥60% reduction in transfusion RBC volume 12-24 months post-drug product infusion compared to the 24 months pre-drug product infusion.6