INDICATIONS

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

REBLOZYL® (luspatercept-aamt) is indicated for the treatment of anemia without previous erythropoiesis stimulating agent use (ESA-naïve) in adult patients with very low- to intermediate-risk myelodysplastic syndromes (MDS) who may require regular red blood cell (RBC) transfusions.

REBLOZYL® (luspatercept-aamt) is indicated for the treatment of anemia failing an erythropoiesis stimulating agent and requiring 2 or more red blood cell (RBC) units over 8 weeks in adult patients with very low- to intermediate-risk myelodysplastic syndromes with ring sideroblasts (MDS-RS) or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T).

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

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PATIENT OUTCOMES: REBLOZYL EFFICACY

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

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

ESA=erythropoiesis-stimulating agent; HbS=hemoglobin S.

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

BELIEVE trial study design BELIEVE trial study design

ESA=erythropoiesis-stimulating agent; HbS=hemoglobin S; SC=subcutaneous injection.

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

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 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)
Sex, n (%)
Male 92 (41.1) 49 (43.7)
Female 132 (58.9) 63 (56.3)
Beta-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

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

Percentage of patients who achieved RBC transfusion reduction in the BELIEVE trial chart Percentage of patients who achieved RBC transfusion reduction in the BELIEVE trial chart

CI=confidence interval; RBC-TI=red blood cell transfusion independence.

4X

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

CI=confidence interval; RBC-TI=red blood cell transfusion independence.

KEY SECONDARY ENDPOINTS

Clinically meaningful reductions in transfusion burden were seen with REBLOZYL1

REBLOZYL® reduction in transfusion burden percentage charts REBLOZYL® reduction in transfusion burden percentage charts

≥50%

Reduction in transfusion burden from baseline of at least 2 units from Weeks 13 to 24

REBLOZYL® reduction in transfusion burden percentage charts REBLOZYL® reduction in transfusion burden percentage charts

≥33%

Reduction in transfusion burden from baseline of at least 2 units from Weeks 37 to 48

REBLOZYL® reduction in transfusion burden percentage charts REBLOZYL® reduction in transfusion burden percentage charts

≥50%

Reduction in transfusion burden from baseline of at least 2 units from Weeks 37 to 48

CI=confidence interval.

Additional analyses

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 transfusions2,3

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 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

PATIENT OUTCOMES: REBLOZYL EFFICACY

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

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

ESA=erythropoiesis-stimulating agent; HbS=hemoglobin S.

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

BELIEVE trial study design BELIEVE trial study design

ESA=erythropoiesis-stimulating agent; HbS=hemoglobin S; SC=subcutaneous injection.

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

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 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)
Sex, n (%)
Male 92 (41.1) 49 (43.7)
Female 132 (58.9) 63 (56.3)
Beta-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

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

Percentage of patients who achieved RBC transfusion reduction in the BELIEVE trial chart Percentage of patients who achieved RBC transfusion reduction in the BELIEVE trial chart

CI=confidence interval; RBC-TI=red blood cell transfusion independence.

4X

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

CI=confidence interval; RBC-TI=red blood cell transfusion independence.

KEY SECONDARY ENDPOINTS

Clinically meaningful reductions in transfusion burden were seen with REBLOZYL1

REBLOZYL® reduction in transfusion burden percentage charts REBLOZYL® reduction in transfusion burden percentage charts

≥50%

Reduction in transfusion burden from baseline of at least 2 units from Weeks 13 to 24

REBLOZYL® reduction in transfusion burden percentage charts REBLOZYL® reduction in transfusion burden percentage charts

≥33%

Reduction in transfusion burden from baseline of at least 2 units from Weeks 37 to 48

REBLOZYL® reduction in transfusion burden percentage charts REBLOZYL® reduction in transfusion burden percentage charts

≥50%

Reduction in transfusion burden from baseline of at least 2 units from Weeks 37 to 48

CI=confidence interval.

Additional analyses

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 transfusions2,3

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 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

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.