EFFICACY

Help them let go of chronic transfusions with ZYNTEGLO1

PATIENTS ≥12 YEARS OF AGE WITH TRANSFUSION-DEPENDENT β-THALASSAEMIA (TDT) WHO DO NOT HAVE A β00 GENOTYPE AND WHO DO NOT HAVE AN HLA-MATCHED RELATED DONOR ARE EVALUATED WITH ZYNTEGLO IN 4 CLINICAL TRIALS AND CONTINUE TO BE FOLLOWED IN A LONG-TERM FOLLOW-UP STUDY FOR UP TO 15 YEARS1

In the pivotal trial 90% of evaluable patients achieved transfusion independence by Month 241

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ZYNTEGLO-derived Hb (HbAT87Q) formed the majority of Hb at 6 months1


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72% of patients (13/18) have stopped iron chelation therapy at last follow-up in the Phase 3 trials1

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TRANSFUSION INDEPENDENCE + TOTAL Hb

In the pivotal trial 90% of evaluable patients achieved transfusion independence* by Month 24†1

of patients who achieved transfusion independence have maintained transfusion independence1

As the Phase 3 trial is ongoing, data shown here are for patients who are currently evaluable for assessment of transfusion independence

80% achieved transfusion independence in Phase 3 studies and 100% maintained it

Data beyond 24 months are from LTF-303

*The primary endpoint was transfusion independence by Month 24, defined as a weighted average Hb ≥9 g/dL without any RBC transfusions for a continuous period of ≥12 months at any time during the study after infusion of ZYNTEGLO.1

†Patients evaluable for transfusion independence, defined as patients who have completed their parent study (i.e. 24 months of follow-up), or achieved transfusion independence, or will not achieve transfusion independence in their parent study.1

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 4 patients who did not achieve transfusion independence experienced transfusion reductions1
Phase 3: HGB-207 (Ongoing) (n=1/10*)1
Phase 3: HGB-207 (Ongoing)
(n=1/10*)1
Patient A showed 51.5% reduction in transfusion volume and 43.4% reduction in transfusion frequency

Reductions observed in the Phase 3 study from Month 12 to Month 24 when compared with pre-study levels of transfusions1

Phase 1/2: HGB-204 + HGB-205 (n=3/14)1
Patient 1 showed 100% reduction in transfusion volume and 100% reduction in transfusion frequency
Patient 2 showed 86.9% reduction in transfusion volume and 85.3% reduction in transfusion frequency
Patient 3 showed 26.8% reduction in transfusion volume and 20.7% reduction in transfusion frequency

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

*Patients evaluable for transfusion independence.
†Patient did not achieve Hb levels ≥9 g/dL, per the definition of transfusion independence.

Exploratory analysis: 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

Median baseline and 12-month myeloid/erythroid ratios (n=9)*1
Range 0.1 through 0.5, n equals 7 of 8
BASELINE
Over approximately 12 months
Range 0.6 through 1.9, n equals 7 of 8
~12 MONTHS AFTER ZYNTEGLO

*Patients who achieved TI and had a Month 12 bone marrow assessment.

†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.

Hb AT 6 MONTHS

ZYNTEGLO-derived Hb (HbAT87Q) formed the majority of Hb at 6 months1

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 HbAT87Q 1

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 9.5 g/dL, minimum 3.4, maximum 10.6. Median total Hb was 11.9 g/dL, minimum 8.4, maximum 13.3
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)

*Patients who have not received transfusions in the prior 60 days.

ZYNTEGLO enables the production of functional gene therapy–derived HbA (HbAT87Q) that can be quantified over time1

REDUCED IRON CONCENTRATION

The majority of patients (13/18) in the Phase 3 trials have stopped iron chelation therapy at last follow-up1
Reduced iron concentration after ZYNTEGLO infusion

Data from beyond 24 months are from LTF-303.
After ZYNTELGO infusion, patient iron levels were managed at physician discretion.

ZYNTEGLO was evaluated in four clinical trials and a long-term follow-up study1,4
  • 45 patients were part of the safety assessment of ZYNTEGLO (≥12 years of age with TDT)1
  • 32 patients were part of the efficacy assessment of ZYNTEGLO (≥12 years of age with non-β00 TDT)1

STUDY DESIGNS

Diagram shows study designs: Phase 1/2 studies HGB-205 and HGB- 204; Phase 3 studies HGB-207 and HGB 212; and LTF-303 ongoing long-term study, up to 15 years planned

 

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 enrollment.1

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 of ZYNTEGLO.1
‡Transfusion reduction defined as ≥60% reduction in transfusion RBC volume 12-24 months post-DP infusion compared to the 24 months pre-drug product.8

PATIENT CHARACTERISTICS

Evaluable patients treated in the four clinical trials for ZYNTEGLO had the following characteristics:1

*2 years prior to date of informed consent.
†Age range is not provided to protect patient identity.