PATIENT OUTCOMES: REBLOZYL EFFICACY

REBLOZYL provided substantial clinical benefit by reducing RBC transfusion burden^1,2

The efficacy of REBLOZYL in patients with beta-thalassemia was demonstrated in the BELIEVE trial

Study design: REBLOZYL was studied in the pivotal Phase 3 BELIEVE trial of 336 adult patients with beta-thalassemia requiring regular RBC transfusions (6-20 RBC units per 24 weeks) with no transfusion-free period greater than 35 days during that period who were randomized 2:1 to REBLOZYL (n=224) or placebo (n=112). In BELIEVE, REBLOZYL was administered subcutaneously once every 3 weeks as long as a reduction in transfusion requirement was observed or until unacceptable toxicity. Patients were able to receive BSC as needed, including: RBC transfusions; iron-chelating agents; use of antibiotic, antiviral, and antifungal therapy; and nutritional support. The exclusion criteria for this trial included HbS/beta-thalassemia or alpha-thalassemia; major organ damage (liver, heart, or lung disease, or renal insufficiency); recent deep vein thrombosis or stroke; or recent use of ESA, immunosuppressant, or hydroxyurea therapy. At 48 weeks, patients could cross over to REBLOZYL as part of the long-term follow-up.^1,3

BELIEVE patient population and study design^1,2

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REBLOZYL was studied in the multicenter, randomized, double-blind, placebo-controlled, Phase 3 BELIEVE trial

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Patient population (N=336)

Key inclusion criteria:

Adults ≥18 years of age with β-thalassemia
Transfusion requirements
- Regular trasfusions 6-20 RBC units per 24 weeks
- No transfusion-free period >35 days during that period

Key exclusion criteria:

HbS/β-thalassemia or isolated α-thalassemia (eg, hemoglobin H)
Major organ damage (liver disease, heart disease, lung disease, renal insufficiency)
Recent deep vein thrombosis or stroke
Recent use of ESA, immunosuppressant, or hydroxyurea therapy

Randomized 2:1 and followed for 48 weeks

REBLOZYL + BSC

1 mg/kg (SC) every 3 weeks, with dose increase allowed to 1.25 mg/kg (n=224)

Placebo + BSC

SC every 3 weeks (n=112)

Long-term follow-up

Optional crossover to REBLOZYL was permitted at 48 weeks

All patients in both arms were eligible to receive best supportive care (BSC) as needed:

RBC transfusions
Iron-chelating agents
Use of antibiotic, antiviral, and antifungal therapy
Nutritional support

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

The intent-to-treat (ITT) population consisted of all patients, regardless of whether the patient received the study drug.

BSC=best supportive care; HbE=hemoglobin E.

Primary endpoint¹

≥33% reduction in RBC transfusion burden of at least 2 units from Weeks 13 to 24

Key secondary endpoints¹

≥50% reduction in RBC transfusion burden from baseline of at least 2 units during Weeks 13 to 24
≥33% and ≥50% reduction in RBC transfusion burden to assess the durability of response from baseline of at least 2 units during Weeks 37 to 48

Additional endpoints²

≥33% or ≥50% reduction from baseline in RBC transfusion burden during any consecutive 24 weeks
Duration of reduction in transfusion burden
Time to erythroid response

All patients in the pivotal Phase 3 BELIEVE trial received regular RBC transfusions¹

BELIEVE baseline disease characteristics^1,2

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Baseline characteristics of patients with beta-thalassemia in the pivotal Phase 3 BELIEVE trial (ITT population)^1,2

Demographic and disease characteristics	REBLOZYL + BSC (n=224)	Placebo + BSC (n=112)
Age, years Median (min, max)	30.0 (18, 66)	30.0 (18, 59)
Baseline transfusion burden 12 weeks prior to randomization, units/12 weeks Median (min, max)	6.12 (3, 14)	6.27 (3, 12)
Beta-thalassemia gene mutation grouping, n (%) β0/β0 Non-β0/β0 Missing^a	68 (30.4) 155 (69.2) 1 (0.4)	35 (31.3) 77 (68.8) 0
Baseline serum ferritin level, μg/L N Median (min, max)	220 1441.25 (88, 6400)	111 1301.50 (136, 6400)
Splenectomy, n (%) Yes No	129 (57.6) 95 (42.4)	65 (58) 47 (42)
Sex, n (%) Male Female	92 (41.1) 132 (58.9)	49 (43.7) 63 (56.3)
Beta-thalassemia diagnosis, n (%) β-thalassemia HbE/ β-thalassemia β-thalassemia combined with α-thalassemia Missing^a	174 (77.7) 31 (13.8) 18 (8) 1 (0.4)	83 (74.1) 21 (18.8) 8 (7.1) 0

^aMissing category includes patients in the population who had no result for the parameter listed.
The intent-to-treat (ITT) population consisted of all patients, regardless of whether the patient received the study drug.

Primary endpoint: RBC-TI ≥33% reduction from baseline in transfusion burden from Weeks 13 to 24¹

21.0% of patients receiving REBLOZYL (n=47/224) vs 4.5% of patients receiving placebo (n=5/112) achieved RBC-TI ≥33% reduction from baseline in transfusion burden from Weeks 13 to 24. Risk Difference (95% CI): 16.5 (9.9-23.1) P<0.0001

4x greater percentage of patients receiving REBLOZYL achieved the primary endpoint vs placebo.

KEY SECONDARY ENDPOINTS

Clinically meaningful reductions in transfusion burden were seen with REBLOZYL¹

7.1% of patients receiving REBLOZYL (n=16/224) vs 1.8% of patients receiving placebo (n=2/112) had ≥50% reduction in transfusion burden from baseline of at least 2 units from Weeks 13 to 24. Risk Difference (95% CI): 5.4 (1.2-9.5) P=0.0402

Greater than or equal to 50% reduction in transfusion burden from baseline of at least 2 units from Weeks 13 to 24

19.6% of patients receiving REBLOZYL (n=44/224) vs 3.6% of patients receiving placebo (n=4/112) had ≥33% reduction in transfusion burden from baseline of at least 2 units from weeks 37 to 48. Risk Difference (95% CI): 16.1 (9.8-22.4) P=0.0001

Greater than or equal to 33% reduction in transfusion burden from baseline of at least 2 units from Weeks 37 to 48

10.3% of patients receiving REBLOZYL (n=23/224) vs 0.9% of patients receiving placebo (n=1/112) had ≥50% reduction in transfusion burden from baseline of at least 2 units from weeks 37 to 48. Risk Difference (95% CI): 9.4 (5.0-13.7) P=0.0017

Greater than or equal to 50% reduction in transfusion burden from baseline of at least 2 unites from Weeks 37 to 48

Additional analyses

Reductions in transfusion burden from baseline during any consecutive 24-week period with REBLOZYL^2,3*

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This analysis looks at the reduction in transfusion burden over a longer period of time, which may be important in adult patients with beta-thalassemia who require regular transfusions^2,3

Endpoint	REBLOZYL (n=224)	Placebo (n=112)	Risk difference (95% CI)
≥33% reduction in transfusion burden, n (%)	92 (41.1)	3 (2.7)	38.4 (31.3-45.5)
≥50% reduction in transfusion burden, n (%)	37 (16.5)	1 (0.9)	15.6 (10.5-20.8)

*Not restricted by a specified time period.

The estimated transfusion burden reduction from baseline per patient based on the consecutive 24-week analysis was²:
- 6.55 RBC units per 24 weeks in patients with ≥33% reduction in RBC transfusion burden
- 8.27 RBC units per 24 weeks in patients with ≥50% reduction in RBC transfusion burden

Analysis limitations³

Patients may have experienced multiple periods of response intermittently between periods without response over the 48-week assessment period
These exploratory analyses should not be interpreted to determine treatment difference between arms in these select endpoints because of potential selection bias, insufficient sample size, and a higher probability of making a false positive finding

Additional analysis information

The total (cumulative) duration of RBC transfusion burden reduction was defined as the sum of individual response periods (≥33% reduction from baseline in RBC transfusion burden of at least 2 units), with overlapping response periods excluded, over the entire 48-week study³
All patients in both arms were eligible to receive BSC as needed: RBC transfusions; iron-chelating agents; use of antibiotic, antiviral, and antifungal therapy; and nutritional support¹

Time to response and total cumulative duration of response at 48 weeks³

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Time from the first dose to response and total (cumulative) duration of response during any consecutive 12-week period³

	REBLOZYL (n=224)	Placebo (n=112)
Patients with ≥33% transfusion burden reduction from baseline of at least 2 units, n (%)	158 (70.5)	33 (29.5)
Time to response, median (min, max)	12 days (2 days, 360 days)	107 days (2 days, 386 days)
Among responders, total cumulative duration of transfusion burden reduction, median (min, max)	298 days (84 days, 631 days)	171 days (84 days, 533 days)

Analysis limitations³

Patients may have experienced multiple periods of response intermittently between periods without response over the 48-week assessment period
These exploratory analyses should not be interpreted to determine treatment difference between arms in these select endpoints because of potential selection bias, insufficient sample size, and a higher probability of making a false positive finding

Additional analysis information

The total (cumulative) duration of RBC transfusion burden reduction was defined as the sum of individual response periods (≥33% reduction from baseline in RBC transfusion burden of at least 2 units), with overlapping response periods excluded, over the entire 48-week study³
The time to response was defined as the first day of the start of the ≥33% reduction from baseline in RBC transfusion burden of at least 2 units during any rolling 12-week period³
Each response period was a continuous period in which a subject had response during any 12-week interval³
The median treatment exposure was approximately 64 weeks in both groups³
All patients in both arms were eligible to receive BSC as needed: RBC transfusions; iron-chelating agents; use of antibiotic, antiviral, and antifungal therapy; and nutritional support¹

BSC=best supportive care; CI=confidence interval; ESA=erythropoiesis-stimulating agent; HbE=hemoglobin E; HbS=hemoglobin S; RBC=red blood cell; RBC-TI=red blood cell transfusion independence; SC=subcutaneous.

Learn about the safety of REBLOZYL

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References: 1. REBLOZYL [US Prescribing Information]. Summit, NJ: Celgene Corporation; 2023. 2. Cappellini MD, Viprakasit V, Taher AT, et al. A phase 3 trial of luspatercept in patients with transfusion-dependent β-thalassemia. N Engl J Med. 2020;382(13):1219-1231. 3. Data on file. Celgene Corporation. Summit, New Jersey.

INDICATIONS

REBLOZYL provided substantial clinical benefit by reducing RBC transfusion burden^1,2

The efficacy of REBLOZYL in patients with beta-thalassemia was demonstrated in the BELIEVE trial

BELIEVE patient population and study design^1,2

All patients in the pivotal Phase 3 BELIEVE trial received regular RBC transfusions¹

BELIEVE baseline disease characteristics^1,2

REBLOZYL + BSC
(n=224)

Placebo + BSC
(n=112)

Primary endpoint: RBC-TI ≥33% reduction from baseline in transfusion burden from Weeks 13 to 24¹

Clinically meaningful reductions in transfusion burden were seen with REBLOZYL¹

Additional analyses

Reductions in transfusion burden from baseline during any consecutive 24-week period with REBLOZYL^2,3*

Endpoint

REBLOZYL
(n=224)

Placebo
(n=112)

Risk difference
(95% CI)

Time to response and total cumulative duration of response at 48 weeks³

REBLOZYL
(n=224)

Placebo
(n=112)

Learn about the safety of REBLOZYL

IMPORTANT SAFETY
INFORMATION

WARNINGS AND PRECAUTIONS

INDICATIONS

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

ADVERSE REACTIONS

LACTATION

DRUG ABUSE POTENTIAL

REBLOZYL provided substantial clinical benefit by reducing RBC transfusion burden1,2

The efficacy of REBLOZYL in patients with beta-thalassemia was demonstrated in the BELIEVE trial

BELIEVE patient population and study design1,2

All patients in the pivotal Phase 3 BELIEVE trial received regular RBC transfusions1

BELIEVE baseline disease characteristics1,2

Primary endpoint: RBC-TI ≥33% reduction from baseline in transfusion burden from Weeks 13 to 241

Clinically meaningful reductions in transfusion burden were seen with REBLOZYL1

Additional analyses

Reductions in transfusion burden from baseline during any consecutive 24-week period with REBLOZYL2,3*

Time to response and total cumulative duration of response at 48 weeks3

Learn about the safety of REBLOZYL

REBLOZYL provided substantial clinical benefit by reducing RBC transfusion burden^1,2

BELIEVE patient population and study design^1,2

All patients in the pivotal Phase 3 BELIEVE trial received regular RBC transfusions¹

BELIEVE baseline disease characteristics^1,2

Primary endpoint: RBC-TI ≥33% reduction from baseline in transfusion burden from Weeks 13 to 24¹

Clinically meaningful reductions in transfusion burden were seen with REBLOZYL¹

Reductions in transfusion burden from baseline during any consecutive 24-week period with REBLOZYL^2,3*

Time to response and total cumulative duration of response at 48 weeks³