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
All of the clinical trials were
designed to measure:
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
Specifically measured total hemoglobin and ZYNTEGLO-derived adult hemoglobin
Iron
Iron reduction (lowering of the amount of iron in the body)
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-β0/β0 | 6
NON-β0/β0* 12 β0/β0 |
|
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-β0/β0 | 6 non-β0/β0 |
| 12 β0/β0 | |
| 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-β0/β0 patients in Study 2 included severe genotypes similar to β0/β0.
†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-β0/β0 patients in Study 2 included severe genotypes similar to β0/β0.
†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 |
|
||
| LOCATION AND ETHNICITY | ||
|
|
49%
ASIAN |
44%
CAUCASIAN |
|
||
Explore Clinical Results:
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.‡
TI: Transfusion Independence
TI: Transfusion Independence
- STUDY 2 represents patients with severe genotypes, including β0/β0 and non-β0/β0 patients with IVS-I-110 genotypes (similar to β0/β0)
| STUDY 1 | STUDY 2 |
| 20/22 patients with non-β0/β0 |
12/14 patients with non-β0/β0, β0/β0 |
| 91% | 86% |
| ACHIEVED TI | ACHIEVED TI |
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.
Time to Last
Transfusion
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) |
Duration of TI
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§
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-β0/β0 |
STUDY 2 12 patients with β0/β0 and non-β0/β0 |
||||||
| 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 | ||||||||
|
||||||||
| 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-β0/β0 |
12 people with β0/β0 and non-β0/β0 |
||||||||||||
| 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
|
|||||||||||||
| 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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