Review the clinical results

ZYNTEGLO® has been studied in two 24-month phase 3 clinical trials, with an ongoing 13-year long-term
follow-up study.1

  • Patients enrolled in the clinical trials had a diagnosis of beta-thalassemia and received regular RBC transfusions (a history of at least 100 mL/kg/year of RBCs or ≥8 transfusions of RBCs per year for the prior 2 years)

41

41

patients treated
with ZYNTEGLO

2

2

open-label, single-arm
clinical trials

Primary outcome for Study 1 (HGB-207) and Study 2 (HGB-212): Transfusion independence1,2
  • Median age: 13 years old (min, max: 4, 34)
  • Genotype:
    • Study 1: 23 non-β00
    • Study 2: 12 β00 and 6 non-β00 (Non-β00 patients were IVS-I-110 homozygous or β0/IVS-I-110)
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89% (n=32/36) of patients across ages and genotypes achieved transfusion independence with a normal or near-normal median total Hb of 11.5 g/dL1*

  • Transfusion independence (89%; 95% CI: 74, 97)
  • Weighted average total Hb during transfusion independence (median 11.5 g/dL; min, max 9.3, 13.7)

The two phase 3 studies are ongoing. All data is as of March 2021.1

91% of patients achieved transfusion independence (n=20/22; 95% CI: 71%, 99%) Median weighted average total Hb during transfusion independence was 11.8 g/dL (min, max: 9.7, 13)‡
86% of patients achieved transfusion independence (n=12/14; 95% CI: 57%, 98%). Global median weighted average total Hb during transfusion independence was 10.2 g/dL (min, max: 9.3, 13.7)‡
100%

All patients (n=32/32) who achieved transfusion independence maintained it.
Min, max duration of ongoing transfusion independence of 12.5+, 39.4+ months; median duration of transfusion independence not reached.

*Across clinical trials, patient evaluability for transfusion independence (n=36) was defined as patients who have completed their parent study (ie, 24 months of follow-up), achieved transfusion independence, or will not achieve transfusion independence in their parent study.1

Normal Hb ranges for healthy individuals from the American College of Clinical Pharmacy3:

  • 2–9 years: 11.5–14.5 g/dL
  • Males 10–17 years: 12.5–16.1 g/dL
  • Females 10–17 years: 12–15 g/dL
  • Male adults (≥18 years): 13.5–18 g/dL
  • Female adults (≥18 years): 12.5–16 g/dL
  • 2–9 years: 11.5–14.5 g/dL
  • Males 10–17 years: 12.5–16.1 g/dL
  • Females 10–17 years: 12–15 g/dL
  • Male adults (≥18 years): 13.5–18 g/dL
  • Female adults (≥18 years): 12.5–16 g/dL

Data beyond 24 months are from the long-term follow-up study, Study 3 (LTF-303).1

All patients who achieved transfusion independence maintained it with durable normal or near-normal total Hb levels1

Median unsupported total Hb was 11.4 g/dL (min, max: 9.5, 14.8) at last follow-up (N=32)

Median total Hb in patients treated with ZYNTEGLO who have achieved transfusion independence4*

Median total Hb in patients treated with ZYNTEGLO who have achieved transfusion independence

This figure is not included in the USPI.

*Bars represent interquartile ranges.
Unsupported total Hb represents those without any pRBC transfusions within 60 days prior to the measurement date. Transfusion independence defined as weighted average hemoglobin ≥9 g/dL without any pRBC transfusions for ≥12 months.1
Data beyond 24 months are from the long-term follow-up study, Study 3 (LTF-303).1

Maximum duration of follow-up was 42 months (N=5), median unsupported total Hb in these
five patients at last follow-up was 13.3 (min, max: 11.1, 13.7) g/dL5

Additional clinical results:
Adult patients

Prespecified subgroup analysis:
Majority of adult patients (18 years of age) across genotypes achieved
transfusion independence with normal or near-normal median total Hb levels6*

The two phase 3 studies are ongoing. All data is as of March 2021.

89% of adult patients achieved transfusion independence (n=8/9). Median weighted average total Hb during transfusion independence was 12.6 g/dL (min, max: 11.7, 13.0)‡89% of adult patients achieved transfusion independence (n=8/9). Median weighted average total Hb during transfusion independence was 12.6 g/dL (min, max: 11.7, 13.0)‡
80% of adult patients achieved transfusion independence (n=4/5). Median weighted average total Hb during transfusion independence was 11.4 g/dL (min, max: 9.3, 13.7)‡80% of adult patients achieved transfusion independence (n=4/5). Median weighted average total Hb during transfusion independence was 11.4 g/dL (min, max: 9.3, 13.7)‡
100%

All adult patients (n=12/12) who achieved transfusion independence maintained it. Min, max duration of ongoing transfusion independence of 13.1+, 39.4+ months; median duration of transfusion independence not reached

Adult subgroup data are not in the USPI. Efficacy in subgroups was not a study objective. There was no hypothesis testing.

*Transfusion independence was defined as weighted average hemoglobin ≥9 g/dL without any packed red blood cell (pRBC) transfusions for ≥12 months.1

Across clinical trials, patient evaluability for transfusion independence (n=36) was defined as patients who have completed their parent study (ie, 24 months of follow-up), achieved transfusion independence, or will not achieve transfusion independence in their parent study.1

Data beyond 24 months are from the long-term study, Study 3 (LTF-303).1

Pediatric patients

Prespecified subgroup analysis:
Majority of pediatric patients (aged 4 to 17) across genotypes achieved
transfusion independence with normal or near-normal median total Hb levels7*

The two phase 3 studies are ongoing. All data is as of March 2021.

92% of pediatric patients achieved transfusion independence (n=12/13). Median weighted average total Hb during transfusion independence was 11.4 g/dL (min, max: 9.7, 12.9)‡92% of pediatric patients achieved transfusion independence (n=12/13). Median weighted average total Hb during transfusion independence was 11.4 g/dL (min, max: 9.7, 12.9)‡
89% of pediatric patients achieved transfusion independence (n=8/9). Median weighted average total Hb during transfusion independence was 10.2 g/dL (min, max: 9.6, 13.2)‡89% of pediatric patients achieved transfusion independence (n=8/9). Median weighted average total Hb during transfusion independence was 10.2 g/dL (min, max: 9.6, 13.2)‡
100%

All pediatric patients (n=20/20) who achieved transfusion independence maintained it.
Min, max duration of ongoing transfusion independence of 12.5+, 37.9+ months; median duration of transfusion independence not reached

Pediatric subgroup data are not in the USPI. Efficacy in subgroups was not a study objective. There was no hypothesis testing.

*Transfusion independence was defined as weighted average hemoglobin ≥9 g/dL without any pRBC transfusions for ≥12 months.1

Across clinical trials, pediatric patient evaluability for transfusion independence (n=22) was defined as patients who have completed their parent study (ie, 24 months of follow-up), have achieved transfusion independence, or will not achieve transfusion independence in their parent study.1

Data beyond 24 months are from the long-term follow-up study, Study 3 (LTF-303).1

The majority of patients (20/32) who achieved transfusion independence are not receiving chelation as of last follow-up1

Restarting iron chelation after ZYNTEGLO infusion may be necessary and should be based on clinical practice*

The two phase 3 studies are ongoing. All data is as of March 2021.1

65% of patients who achieved TI no longer receiving chelation

Of those 13 patients

  • 9 did not restart chelation post-ZYNTEGLO infusion
  • 4 restarted and then stopped with a median time from last iron chelation use to last follow-up of 22.7 months (min, max: 7.1, 23.4)

Of the 20 patients who achieved transfusion independence, 7 patients (35.0%) received phlebotomy to remove iron1

58% of patients who achieved TI no longer receiving chelation

Of those 7 patients

  • 3 did not restart chelation post-ZYNTEGLO infusion
  • 4 restarted and then stopped with a median time from last iron chelation use to last follow-up of 7.2 months (min, max: 6.0, 21.4)

Of the 12 patients who achieved transfusion independence, 1 patient (8%) received phlebotomy to remove iron 

*Prior to initiation of conditioning for ZYNTEGLO, iron removal therapies should be stopped for at least 7 days. In the clinical studies, iron removal therapy after ZYNTEGLO infusion was managed at physician discretion.1

Median time to last RBC transfusion prior to transfusion independence was <1 month1*

Transfusion independence

Study 1 (median): 0.9 months (n=20; min, max: 0.5, 2.4 months)
Study 2 (median): 0.8 months (n=12; min, max: 0.0, 1.9 months)

*Transfusion independence was defined as weighted average hemoglobin ≥9 g/dL without any pRBC transfusions for ≥12 months.1 

Patients who were evaluable for transfusion independence but did not achieve it experienced transfusion reductions1*

Reductions were observed from 6 months post-ZYNTEGLO infusion to last follow-up compared to pre-enrollment requirements

The two phase 3 studies are ongoing. All data is as of March 2021.1

STUDY 1: (n=2/22)
Patient 3A
Transfusion frequency: 30% reduction
Transfusion volume: 32% reduction
Patient 3B
Transfusion frequency: 26% reduction
Transfusion volume: 31% reduction
Transfusion volume: 31% reduction
STUDY 2:  (n=2/14)
Patient 3C
Transfusion frequency: 87% reduction
Transfusion volume: 92% reduction
Patient 3D
Transfusion frequency: 21% reduction
Transfusion volume: 3% reduction
Transfusion volume: 3% reduction

*Transfusion independence was defined as weighted average Hb of ≥9 g/dL without any pRBC transfusions for ≥12 months.1

Data shown here are for patients who are currently evaluable for assessment of transfusion independence as of March 2021. 

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