EFFICACY

FOR YOUR PATIENTS ≥12 YEARS OF AGE WITH TRANSFUSION-DEPENDENT β-THALASSAEMIA (TDT) WHO DO NOT HAVE A β00 GENOTYPE, FOR WHOM HAEMATOPOIETIC STEM CELL (HSC) TRANSPLANTATION IS APPROPRIATE, AND WHO DO NOT HAVE A HUMAN LEUKOCYTE ANTIGEN (HLA)-MATCHED RELATED DONOR1

Help them let go of chronic transfusions1

ZYNTEGLO was evaluated in four clinical trials and a long-term follow-up study1,7

The majority of patients* treated with ZYNTEGLO achieved transfusion independence. All patients who achieved transfusion independence maintained it at last follow-up.1

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*Defined as patients who have completed the parent study and achieved transfusion independence or will not achieve transfusion independence in the parent study.1

ZYNTEGLO enables the production of functional gene therapy-derived HbA (HbAT87Q) that can be quantified by bluebird bio over time.1


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Reduced iron overload was shown at 48 months for patients in HGB-204 and HGB-205 who achieved transfusion independence.1



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Data from beyond 24 months are from LTF-303.7


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
Graphic showing Phase 1/2 transfusion independence data
100% maintained transfusion independence at Month 36 (min, max: 28.3+, 57.6+)

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.

Graphic showing Phase 3 transfusion independence data
100% maintained transfusion independence (min, max: 12.1+, 21.3+ months)

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-β00 TDT patients treated with ZYNTEGLO who have achieved transfusion independence1
Chart shows total Hb levels maintained above 9 g/dL over 60 months for HGB-207, HGB-205, and HGB-204

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
The four patients with non-β00 TDT who did not achieve transfusion independence experienced transfusion reductions1
HGB-204 + HGB-2051 (n=3/14)

Reductions observed in the Phase 1/2 studies between Month 6 and Month 24 visits when compared with their pre-study levels of transfusions1

*Patient did not achieve weighted average Hb levels ≥9 g/dL, per the definition of transfusion independence.1

HGB-207 (ONGOING)1 (n=1/10*)

Reductions observed from month 12 to month 24 when compared to their pre-study levels of transfusions1

Patients evaluable for transfusion independence.1

TOTAL Hb DURING TRANSFUSION INDEPENDENCE

Patients treated with ZYNTEGLO achieved Hb levels that enabled transfusion independence1
Median Hb levels in patients with non-β00 TDT achieving transfusion independence1
Median 10.5 g/dl

HGB-204 + HGB-205
(n=11)

Weighted average Hb during transfusion independence.

Phase 1/2 - COMPLETED1

Median Hb for ongoing Phase 3 study was 12.2 g/dL, minimum 11.4, maximum 12.8

HGB-207
(n=9)

Weighted average Hb during transfusion independence.

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
Median HbAT87Q was 9.3 g/dL, minimum 3.4, maximum 10.6. Median total Hb was 11.8 g/dL, minimum 8.4, maximum 13.3

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)
Data from beyond 24 months are from LTF-303.7
Serum ferritin was reduced 70% from baseline. Median baseline serum ferritin was 3778.7 pmol/L, minimum 784, maximum 22517.
MEDIAN CHANGE FROM BASELINE IN SERUM FERRITIN1
Liver iron content was reduced 62.5% from baseline. Median baseline LIC was 6.75 mg/g, minimum 1.0, maximum 41.0.
MEDIAN CHANGE FROM BASELINE IN LIC1
  • After Zynteglo infusion, patient iron chelation was managed at physician discretion.1
  • Of the 14 non-β00 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
Over approximately 12 months
~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-β00 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-β00 genotype (N=10, HGB-204, N=4, HGB-205) and 8 had a β00-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