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Pivotal phase 3 BELIEVE trial design

REBLOZYL was evaluated in the phase 3, multicenter, randomized, double-blind, placebo-controlled BELIEVE trial of 336 adult patients with β-thalassemia requiring regular RBC transfusions (6–20 RBC units per 24 weeks).1

Pivotal Phase 3 BELIEVE Trial Design.
Pivotal Phase 3 BELIEVE Trial Design.

Primary endpoint1

  • The efficacy of REBLOZYL was established based upon the proportion of patients achieving RBC transfusion burden reduction (≥33% reduction from baseline) with a reduction of at least 2 units from week 13 to week 24

Baseline characteristics

Baseline disease characteristics of β-thalassemia in BELIEVE1

Disease
characteristics
REBLOZYL
(n = 224)
Placebo
(n = 112)
β-thalassemia diagnosis, n (%)
β-thalassemia 174 (77.7) 83 (74.1)
HbE/β-thalassemia 31 (13.8) 21 (18.8)
β-thalassemia combined with α‑thalassemia 18 (8) 8 (7.1)
Missinga 1 (0.4) 0
Baseline transfusion burden 12 weeks prior to randomization, units/12 weeks
Median (min, max) 6.12 (3, 14) 6.27 (3, 12)
β-thalassemia gene mutation grouping, n (%)
β0/β0 68 (30.4) 35 (31.3)
Non-β0/β0 155 (69.2) 77 (68.8)
Missinga 1 (0.4) 0
Baseline serum ferritin level, μg/L
N 220 111
Median (min, max) 1441.25 (88, 6400) 1301.50 (136, 6400)
Splenectomy, n (%)
Yes 129 (57.6) 65 (58)
No 95 (42.4) 47 (42)
Age patient started regular transfusions, years
N 169 85
Median (min, max) 2 (0, 52) 2 (0, 51)

aMissing category includes patients in the population who had no result for the parameter listed.

HbE, hemoglobin E.

  • The median age was 30 years (range, 18–66)1
  • 42% of patients were male1
  • 54.2% of patients were white, 34.8% were Asian, 0.3% were black or African American, 7.7% reported their race as “other,” and 3% were not collected1

Reduction in transfusion burden from baseline in the phase 3 BELIEVE trial

Efficacy results in β-thalassemia—BELIEVE1

Endpoint REBLOZYL
(n = 224)
Placebo
(n = 112)
Risk difference
(95% CI)
P value
≥33% reduction from baseline in RBC transfusion burden with a reduction of at least 2 units for 12 consecutive weeks
Primary endpoint:
Weeks 13–24
48
(21.4)
5
(4.5)
17.0
(10.4–23.6)
<0.0001
Weeks
37–48
44
(19.6)
4
(3.6)
16.1
(9.8–22.4)
<0.0001
≥50% reduction from baseline in RBC transfusion burden with a reduction of at least 2 units for 12 consecutive weeks
Weeks
13–24
17
(7.6)
2
(1.8)
5.8
(1.6–10.1)
0.0303
Weeks
37–48
23
(10.3)
1
(0.9)
9.4
(5–13.7)
0.0017

Significantly more patients receiving REBLOZYL achieved the primary endpoint compared with placebo (21.4% vs 4.5%, respectively; P < 0.0001)1

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Indication

REBLOZYL is indicated for the treatment of anemia in adult patients with beta thalassemia who require regular red blood cell (RBC) transfusions.

REBLOZYL is not indicated for use as a substitute for RBC transfusions in patients who require immediate correction of anemia.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Thrombosis/Thromboembolism: Thromboembolic events (TEE) were reported in 8/223 (3.6%) REBLOZYL-treated patients. TEEs included deep vein thrombosis, pulmonary embolus, portal vein thrombosis, and ischemic stroke. Patients with known risk factors for thromboembolism (splenectomy or concomitant use of hormone replacement therapy) may be at further increased risk of thromboembolic conditions. Consider thromboprophylaxis in patients at increased risk of TEE. Monitor patients for signs and symptoms of thromboembolic events and institute treatment promptly.

Hypertension

Hypertension was reported in 10.7% (61/571) of REBLOZYL-treated patients. Across clinical studies, the incidence of Grade 3 to 4 hypertension ranged from 1.8% to 8.6%. In patients with beta thalassemia with normal baseline blood pressure, 13 (6.2%) patients developed systolic blood pressure (SBP) >130 mm Hg and 33 (16.6%) patients developed diastolic blood pressure (DBP) >80 mm Hg. Monitor blood pressure prior to each administration. Manage new or exacerbations of preexisting hypertension using anti-hypertensive agents.

Embryo-Fetal Toxicity

REBLOZYL may cause fetal harm when administered to a pregnant woman. REBLOZYL caused increased post-implantation loss, decreased litter size, and an increased incidence of skeletal variations in pregnant rat and rabbit studies. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 3 months after the last dose.

ADVERSE REACTIONS

Serious adverse reactions occurring in 1% of patients included cerebrovascular accident and deep vein thrombosis. A fatal adverse reaction occurred in 1 patient treated with REBLOZYL who died due to an unconfirmed case of acute myeloid leukemia (AML).

Most common adverse reactions (at least 10% for REBLOZYL and 1% more than placebo) were headache (26% vs 24%), bone pain (20% vs 8%), arthralgia (19% vs 12%), fatigue (14% vs 13%), cough (14% vs 11%), abdominal pain (14% vs 12%), diarrhea (12% vs 10%) and dizziness (11% vs 5%).

LACTATION

It is not known whether REBLOZYL is excreted into human milk or absorbed systemically after ingestion by a nursing infant. REBLOZYL was detected in milk of lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk. Because many drugs are excreted in human milk, and because of the unknown effects of REBLOZYL in infants, a decision should be made whether to discontinue nursing or to discontinue treatment. Because of the potential for serious adverse reactions in the breastfed child, breastfeeding is not recommended during treatment and for 3 months after the last dose.

Please see full Prescribing Information for REBLOZYL.

Reference: 1. REBLOZYL [Prescribing Information]. Summit, NJ: Celgene Corporation; 2019.