Clinical Results

ZYNTEGLO® clinical trials overview

  • In two phase 3 studies, ZYNTEGLO was studied in 41 patients
  • All studies of ZYNTEGLO were open label, meaning that study participants and their doctors knew they were receiving ZYNTEGLO
  • Each study ran for an initial 24-month period to assess transfusion independence

41

41

patients treated in
phase 3 clinical trials

patients treated in
phase 3 clinical trials

2

2

clinical
trials

clinical
trials

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All of the clinical trials were
designed to measure:

Transfusion Independence

Transfusion Independence

The weighted average hemoglobin greater than or equal to 9 g/dL without any blood transfusions for a continuous period greater than or equal to 12 months

Hemoglobin

Hemoglobin

Specifically measured total hemoglobin and ZYNTEGLO-derived adult hemoglobin

Iron Reduction

Iron

Iron reduction (lowering of the amount of iron in the body)

Efficacy and Safety

Safety

Evaluate adverse effects that occur

Clinical trial patients receiving ZYNTEGLO continue to be followed long term, with 7 patients
who have completed their 3.5-year follow-up visit

Those eligible for clinical trials were patients with beta-thalassemia (also known as beta-thalassemia
major or Cooley's Anemia) requiring regular transfusions categorized as either:

In the 2 years before entering the trial:

  • At least 100 mL/kg/year of red blood cells, or
  • Eight or more regular red blood cell transfusions per year

PHASE 3: ONGOING (AS OF MARCH 2021)

STUDY 1 STUDY 2
NUMBER OF
PARTICIPANTS
23 TOTAL 18 TOTAL
14 PEDIATRICS
9 ADULTS
13 PEDIATRICS
5 ADULTS
AGE (YEARS) 4-34 4-33
GENOTYPES 23 NON-β00 6 NON-β00*
12 β00
PRIMARY
OUTCOME
Transfusion Independence
Phase 3: Ongoing
(As of MARCH 2021)
STUDY 1 STUDY 2
NUMBER OF PARTICIPANTS NUMBER OF PARTICIPANTS
23 Total 18 Total
14 pediatrics
9 adults
13 pediatrics
5 adults
AGE (YEARS)
4-34 4-33
Genotypes Genotypes
23 non-β00 6 non-β00
12 β00
PRIMARY
OUTCOME
Transfusion Independence
STUDY 1 STUDY 2
MEDIAN
FOLLOW-UP
STUDY
29.5
MONTHS
(min, max: 13.0, 48.2)
24.6
MONTHS
(min, max: 4.1, 35.5)
ENROLLED IN
FOLLOW-UP
STUDY
19/23
PATIENTS
10/18
PATIENTS
*Non-β00 patients in Study 2 included severe genotypes similar to β00.
Remaining patients are still in the process of completing their initial clinical trial before they have the option to continue in the follow-up study.
Pediatric is defined as people under the age of 18.
median
follow-up
study
median
follow-up
study
29.5 24.6
Months
(min, max: 13.0, 48.2)
Months
(min, max: 4.1, 35.5)
ENROLLED IN
FOLLOW-UP
STUDY
ENROLLED IN
FOLLOW-UP
STUDY
19/23 10/18
PATIENTS* PATIENTS*
*Non-β00 patients in Study 2 included severe genotypes similar to β00.
Remaining patients are still in the process of completing their initial clinical trial before they have the option to continue in the follow-up study.
Pediatric is defined as people under the age of 18.

Characteristics of all study
participants (N=41)

GENDER
49%
FEMALE
51%
MALE
LOCATION AND ETHNICITY
49%
ASIAN
44%
WHITE/CAUCASIAN
  • France
  • Germany
  • Greece
  • Italy
  • Thailand
  • UK
  • US
LOCATION AND ETHNICITY
57.1%
ASIAN
38.1%
CAUCASIAN
  • Australia
  • France
  • Germany
  • Italy
  • Thailand
  • UK
  • US
89 percent
In two phase 3 studies, about 9 out of 10 (89%) patients treated with ZYNTEGLO stopped transfusions

Transfusion independence (TI) meant that patients achieved a weighted average hemoglobin of ≥9 g/dL without any transfusions for a continuous period of ≥12 months at any time during the study after infusion of ZYNTEGLO.

The majority of patients achieved transfusion independence (89%; 32/36 patients) and had a normal to near-normal median total hemoglobin of 11.5 g/dL.

Transfusion Independence

TI: Transfusion Independence

Transfusion Independence

TI: Transfusion Independence

  • STUDY 2 represents patients with severe genotypes, including β00 and non-β00 patients with IVS-I-110 genotypes (similar to β00)
STUDY 1 STUDY 2
20/22 patients
with non-β00
12/14 patients with
non-β00, β00
91% 86%
ACHIEVED TI ACHIEVED TI
Median total hemoglobin level

Median Total Hemoglobin Level

Median total hemoglobin level

Median Total Hemoglobin Level

Patients who achieved transfusion independence (32/36) had a near-normal median total hemoglobin level driven by ZYNTEGLO-derived adult hemoglobin

STUDY 1 STUDY 2
MEDIAN TOTAL Hb MEDIAN TOTAL Hb
11.8g/dL 10.2g/dL

Total hemoglobin levels presented on this page reflect weighted average total hemoglobin during transfusion independence, which is defined as the average across hemoglobin levels taken at each patient visit during the clinical study, factoring in a weighting based on the time duration between study visits

Results shown are from TI evaluable patients in phase 3 studies only

Results shown are for the 36 out of 41 patients currently evaluable in STUDY 1 and STUDY 2. Patients are evaluable if they have completed 24 months of follow-up in the phase 3 study, or achieved transfusion independence, or won't achieve transfusion independence in the phase 3 study.

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

  • 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

Patients unable to achieve transfusion independence still reduced transfusions 

In the phase 3 trials, 4 out of 36 patients who were evaluated for transfusion independence
didn't achieve it, but were still able to: 

  • Reduce red blood cell transfusion frequency
  • Reduce red blood cell transfusion volume 

RESULTS FROM PHASE 3
CLINICAL TRIALS

STUDY 1
PATIENT 1 PATIENT 2
30%
TRANSFUSION
FREQUENCY
REDUCTION
32%
TRANSFUSION
VOLUME
REDUCTION
26%
TRANSFUSION
FREQUENCY
REDUCTION
31%
TRANSFUSION
VOLUME
REDUCTION
STUDY 1
PATIENT 1
30%
TRANSFUSION
FREQUENCY
REDUCTION
32%
TRANSFUSION
VOLUME
REDUCTION
PATIENT 2
26%
TRANSFUSION
FREQUENCY
REDUCTION
31%
TRANSFUSION
VOLUME
REDUCTION
STUDY 2
PATIENT 3 PATIENT 4
87%
TRANSFUSION
FREQUENCY
REDUCTION
92%
TRANSFUSION
VOLUME
REDUCTION
21%
TRANSFUSION
FREQUENCY
REDUCTION
3%
TRANSFUSION
VOLUME
REDUCTION
STUDY 2
PATIENT 3
87%
TRANSFUSION
FREQUENCY
REDUCTION
92%
TRANSFUSION
VOLUME
REDUCTION
PATIENT 4
21%
TRANSFUSION
FREQUENCY
REDUCTION
3%
TRANSFUSION
VOLUME
REDUCTION

Reductions observed in phase 3 clinical trials from 6 months post-ZYNTEGLO infusion to the
patient's last follow-up visit when compared with their pre-enrollment transfusion requirements.


Transfusion Independence

Time to Last
Transfusion

Transfusion Independence

Time to Last Transfusion

The patients who achieved transfusion independence had their last transfusion prior to achieving transfusion independence at a median time of about 4 weeks post ZYNTEGLO infusion.

STUDY 1 STUDY 2
MEDIAN
OF 4
MEDIAN
OF 3-4
WEEKS WEEKS
(min, max: 0.5, 2.4 months) (min, max: 0.0, 1.9 months)
100 percent

Duration of TI

100 percent

Duration of TI

100% of patients (n=32/32) who have achieved transfusion independence maintained it with a min, max duration of ongoing transfusion independence of 12.5+ to 39.4+ months. Median duration of transfusion independence was not reached.

No differences in efficacy or clinical safety were observed between pediatrics (pediatric is defined as people under the age of 18) and adults.

Engraftment times were longer in pediatrics but not associated with increases in infections or bleeding events.

Iron Chelation

Iron Chelation§

Iron Chelation

Iron Chelation§

The majority of patients who achieved transfusion independence were not receiving chelation as of last follow-up

RESULTS FROM PHASE 3
CLINICAL TRIALS

Patients who achieved
transfusion independence
STUDY 1
20 patients with
non-β00
STUDY 2
12 patients with
β00 and non-β00
WERE NOT RECEIVING CHELATION
AT LAST FOLLOW-UP
65%
(13/20 patients)
58%
(7/12 patients)
Of those who were not on chelation at last follow-up
DID NOT RESTART CHELATION 69%
(9/13 patients)
43%
(3/7 patients)
RESTARTED THEN STOPPED
CHELATION
31%
(4/13 patients)
57%
(4/7 patients)
RECEIVED PHLEBOTOMY
TO REMOVE IRON
35%
(7/20 patients)
8%
(1/12 patients)
§Iron removal therapy was managed at a doctor's discretion. Restarting iron chelation after ZYNTEGLO may be necessary.
Patients who achieved
transfusion independence
STUDY 1 STUDY 2
20 people with
non-β00
12 people with β00
and non-β00
WERE NOT RECEIVING CHELATION AT LAST FOLLOW-UP
65% 58%
(13/20 people) (7/12 people)
Of those who were not on chelation at last follow-up
Did not restart chelation
69% 43%
(9/13 people) (3/7 people)
Restarted then stopped chelation
31% 57%
(4/13 people) (4/7 people)
Received phlebotomy to remove iron
35% 8%
(7/20 people) (1/12 people)
§Iron removal therapy was managed at a doctor's discretion. Restarting iron chelation after ZYNTEGLO may be necessary.
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