EFFICACY
Help them let go of chronic transfusions with ZYNTEGLO1
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
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-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
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
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
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
BASELINE
~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 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 TOTAL Hb AT 6 MONTHS*1
MEDIAN TOTAL Hb
AT 6 MONTHS*1
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-β0/β0 TDT)1
STUDY DESIGNS
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-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 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.
