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 or 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 are currently eligible for assessment of 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 phase 1/2 trials and LTF-303 (min, max) is up to 58.6 months (29.3, 58.6)1
- Follow-up in the ongoing phase 3 trials (min, max) is up to 22.2 months (1.3, 22.2)1
Median total Hb over time in non-β0/β0 TDT patients treated with ZYNTEGLO who have achieved transfusion independence1
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=4)
(n=4)
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 patients at 6 months who did not receive a transfusion for the prior 60 days6
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 11.9 g/dL, primarily driven by HbAT87Q 6
Phase 3 study
HGB-207
(n=11)
MEDIAN HbAT87Q AT 6 MONTHS1,6
MEDIAN TOTAL Hb AT 6 MONTHS1,6
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 cells.1
Phase 1/2
studies
HGB-204 (n=10)1,6:
4.2 g/dL (min, max: 1.0, 8.5)
HGB-205 (n=4)1,6:
7.5 g/dL (min, max: 4.9, 9.6)
HGB-204 (n=7)1,6:
9.2 g/dL (min, max: 7.7, 13.3)
HGB-205 (n=4)1,6:
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 over time.6
REDUCED IRON CONCENTRATION
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=3, HGB-204; n=2, HGB-205)
MEDIAN CHANGE FROM BASELINE IN SERUM FERRITIN1
MEDIAN CHANGE FROM BASELINE IN LIC1
- After ZYNTEGLO infusion, patient iron levels were managed at physician discretion.1
- All patients in HGB-204 restarted iron chelation and continue to use iron chelators. One patient in HGB-205 restarted iron chelation and continues to use iron chelators. Three patients in HGB-205 started phlebotomy.1
- Of the 11 patients followed for at least 6 months after ZYNTEGLO infusion in HGB-207 and HGB-212, 6 patients did not restart iron chelation or receive phlebotomy, 3 patients restarted iron chelation, and 2 patients received phlebotomy to reduce iron levels.1
Erythropoiesis: ZYNTEGLO increases myeloid/erythroid ratios1
In an exploratory analysis from HGB-207, bone marrow biopsies taken before ZYNTEGLO infusion showed low myeloid/erythroid ratios (n=15), reflective of erythroid hyperplasia and consistent with a diagnosis of TDT1
Baseline and 12-month myeloid/erythroid ratios (n=8)1*
BASELINE MYELOID/ERYTHROID RATIO
~12 MONTHS AFTER ZYNTEGLO MYELOID/ERYTHROID RATIO
*Patients who had sufficient on-study follow-up to obtain a 12-month bone marrow assessment.1
**For 8 patients who had sufficient on-study follow-up to obtain a 12-month follow-up bone marrow assessment, myeloid/erythroid ratios for 7 patients increased from a range of 0.1 to 0.5 at baseline to a range of 0.6 to 1.9 approximately 12 months after ZYNTEGLO infusion.1
ZYNTEGLO was evaluated in four clinical trials and a long-term follow-up study1,7
-
42 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
STUDY DESIGNS
Patients were assessed for transfusion independence*
-
Open-label
-
Single-arm
-
Patients had a history of RBC transfusions of ≥100 mL/kg/year or ≥8 transfusions per year in the 2 years prior to enrolment
*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.
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. 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
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.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.6