INDICATIONS

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

REBLOZYL is indicated for the treatment of anemia failing an erythropoiesis stimulating agent and requiring 2 or more red blood cell 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

With REBLOZYL, you can now
achieve transfusion independence
AND hematologic improvement1

Study design: REBLOZYL was studied in the pivotal phase 3 MEDALIST trial of 229 patients with IPSS-R very low-, low-, or intermediate-risk MDS who have ring sideroblasts and require RBC transfusions (≥2 RBC units/8 weeks) who were randomized 2:1 to REBLOZYL (n=153) or placebo (n=76). Patients were required to have had an inadequate response to prior treatment with an ESA, be intolerant of ESAs, or be ineligible for ESAs (serum EPO >200 U/L). MEDALIST excluded patients with del(5q) MDS, white blood cell count >13 Gi/L, neutrophils <0.5 Gi/L, platelets <50 Gi/L, or with prior use of a disease-modifying agent for treatment of MDS. REBLOZYL was administered 1 mg/kg subcutaneously every 3 weeks.1

EPO=erythropoietin; ESA=erythropoiesis-stimulating agent; IPSS-R=Revised International Prognostic Scoring System; MDS=myelodysplastic syndromes; RBC=red blood cell.

REBLOZYL was studied in the multicenter, randomized, double-blind, placebo-controlled, phase 3 MEDALIST trial1,2

MEDALIST trial design MEDALIST trial design

*The primary efficacy assessment was conducted after completion of 24 weeks on study drug. Patients with a decrease in transfusion requirement or increase in Hgb could continue on blinded study drug thereafter until unacceptable toxicity, loss of efficacy, or disease progression.

SC=subcutaneous injection.

The MEDALIST trial included patients with very low- to intermediate-risk MDS with ring sideroblasts1,3,4

Demographic and disease characteristics REBLOZYL
(n=153)
Placebo
(n=76)
Age, years
Median (min, max) 71.0 (40, 95) 72.0 (26, 91)
Time since original MDS diagnosis,a months
Median (min, max) 44.0 (3, 421) 36.1 (4, 193)
Serum EPO (U/L) categories,b n (%)
<200
200 to 500
>500
Missing
88 (57.5)
43 (28.1)
21 (13.7)
1 (0.7)
50 (65.8)
15 (19.7)
11 (14.5)
0
RBC transfusion/8 weeks over 16 weeks, n (%)
<4 units
≥4 and <6 units
≥6 units
46 (30.1)
41 (26.8)
66 (43.1)
20 (26.3)
23 (30.3)
33 (43.4)
Diagnosis per WHO 2016 criteria,c n (%)
MDS-RSd
MDS/MPN-RS-T
Othere
135 (88.2)
14 (9.2)
4 (2.6)
65 (85.5)
9 (11.8)
2 (2.6)
SF3B1, n (%)
Mutated
Nonmutated
Missing
138 (93.2)
10 (6.8)
0
64 (86.5)
10 (13.5)
1 (1.3)
IPSS-R classification risk category, n (%)
Very low
Low
Intermediate
High
18 (12)
109 (71)
25 (16)
1 (1)
6 (8)
57 (75)
13 (17)
0

aTime since original MDS diagnosis was defined as the number of months from the date of original diagnosis to the date of informed consent. bBaseline EPO was defined as the highest EPO value within 35 days of the first dose of study drug. cMEDALIST enrolled patients with MDS with ring sideroblasts per the WHO 2008 criteria; however, these data are based on post hoc reclassification of patients by the FDA using the WHO 2016 diagnostic criteria (MDS-RS [n=200; 87.3%], MDS/MPN-RS-T [n=23; 10.0%], and Other [n=6; 2.6%]). dIncludes MDS-RS-MLD and MDS-RS-SLD. eIncludes MDS-EB-1, MDS-EB-2, and MDS-U, which met the criteria for inclusion of ring sideroblasts ≥15% of erythroid precursors in the bone marrow or ≥5% (but <15%) if SF3B1 mutation was present.

*Numbers in callouts are based on the entire clinical trial population.

FDA=Food and Drug Administration; MDS-EB-1=myelodysplastic syndromes with excess blasts (5%-9% in the bone marrow or 2%-4% in the blood); MDS-EB-2=myelodysplastic syndromes with excess blasts (10%-19% in the bone marrow or 5%-19% in the blood); MDS-RS-MLD=MDS with multiple lineage dysplasia and ring sideroblasts; MDS-RS-SLD=MDS with single lineage dysplasia and ring sideroblasts; MDS-U=myelodysplastic syndromes, unclassifiable; WHO=World Health Organization.

Primary endpoint: RBC-TI ≥8 weeks during weeks 1 to 241

REBLOZYL® efficacy graph REBLOZYL® efficacy graph

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

APPROXIMATELY

3X

greater percentage of patients receiving REBLOZYL achieved RBC transfusion independence than placebo

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

60% (35/58)

of responders required at least 1 dose increase to achieve RBC-TI2

REBLOZYL had a significantly higher rate of RBC transfusion independence vs placebo for 12 weeks or more1

Key secondary endpoints: RBC-TI ≥12 weeks1

MEDALIST trial key secondary endpoints graph MEDALIST trial key secondary endpoints graph MEDALIST trial key secondary endpoints graph

*The median (range) duration of treatment was 49 weeks (6-114 weeks) on the REBLOZYL arm and 24 weeks (7-89 weeks) on the placebo arm.

RBC-TI ≥8 weeks during Weeks 1 to 24 by diagnosis and baseline transfusion burden in MEDALIST1

Responders/N % Response (95% CI)
REBLOZYL Placebo REBLOZYL Placebo
WHO 2016 diagnosis
MDS-RS 46/135 8/65 34.1 (26.1, 42.7) 12.3 (5.5, 22.8)
MDS/MPN-RS-T 9/14 2/9 64.3 (35.1, 87.2) 22.2 (2.8, 60.0)
Othera 3/4 0/2 75.0 (19.4, 99.4) 0.0 (0.0, 84.2)
Baseline RBC transfusion burden
2-3 units/8 weeksb 37/46 8/20 80.4 (66.1, 90.6) 40.0 (19.1, 63.9)
4-5 units/8 weeksc 15/41 1/23 36.6 (22.1, 53.1) 4.3 (0.1, 21.9)
≥6 units/8 weeks 6/66 1/33 9.1 (3.4, 18.7) 3.0 (0.1, 15.8)
Responders/N
REBLOZYL Placebo
WHO 2016 diagnosis
MDS-RS 46/135 8/65
MDS/MPN-RS-T 9/14 2/9
Othera 3/4 0/2
Baseline RBC transfusion burden
2-3 units/8 weeksb 37/46 8/20
4-5 units/8 weeksc 15/41 1/23
≥6 units/8 weeks 6/66 1/33
% Response (95% CI)
REBLOZYL Placebo
WHO 2016 diagnosis
MDS-RS 34.1
(26.1, 42.7)
12.3
(5.5, 22.8)
MDS/MPN-RS-T 64.3
(35.1, 87.2)
22.2
(2.8, 60.0)
Othera 75.0
(19.4, 99.4)
0.0
(0.0, 84.2)
Baseline RBC transfusion burden
2-3 units/8 weeksb 80.4
(66.1, 90.6)
40.0
(19.1, 63.9)
4-5 units/8 weeksc 36.6
(22.1, 53.1)
4.3
(0.1, 21.9)
≥6 units/8 weeks 9.1
(3.4, 18.7)
3.0
(0.1, 15.8)

aIncludes MDS-EB-1, MDS-EB-2, and MDS-U. bIncludes patients who received 3.5 units. cIncludes patients who received 5.5 units.

MDS-EB-1=myelodysplastic syndromes with excess blasts (5%-9% in the bone marrow or 2%-4% in the blood); MDS-EB-2=myelodysplastic syndromes with excess blasts (10%-19% in the bone marrow or 5%-19% in the blood); MDS-U=myelodysplastic syndromes, unclassifiable; WHO=World Health Organization.


Additional analysis: Modified hematologic improvement-erythroid (mHI-E) was assessed in patients receiving REBLOZYL2

mHI-E was defined per the IWG criteria as the proportion of patients who met mHI-E criteria sustained over any consecutive 56-day (8-week) period2:

  • For patients with baseline RBC transfusion burden of at least 4 units/8 weeks: response was defined as a reduction in RBC transfusion burden of ≥4 RBC units/8 weeks
  • For patients with baseline RBC transfusion burden of less than 4 units/8 weeks: response was defined as a mean Hgb increase of ≥1.5 g/dL/8 weeks in the absence of transfusions for at least 8 weeks

Hgb=hemoglobin; IWG=International Working Group.


Patients achieving mHI-E in MEDALIST2

Weeks 1-24 Weeks 1-48
REBLOZYL
(n=153)
Placebo
(n=76)
REBLOZYL
(n=153)
Placebo
(n=76)
Modified hematologic improvement-erythroid (mHI-E) 52.9%
(81/153)
11.8%
(9/76)
58.8%
(90/153)
17.1%
(13/76)
RBC transfusion reduction of ≥4 units/8 weeksa 48.6%
(52/107)
14.3%
(8/56)
54.2%
(58/107)
21.4%
(12/56)
Hgb increase of ≥1.5 g/dL for 8 weeksb 63.0%
(29/46)
5.0%
(1/20)
69.6%
(32/46)
5.0%
(1/20)
Weeks 1-24
REBLOZYL
(n=153)
Placebo
(n=76)
Modified hematologic improvement-erythroid (mHI-E) 52.9%
(81/153)
11.8%
(9/76)
RBC transfusion reduction of ≥4 units/8 weeksa 48.6%
(52/107)
14.3%
(8/56)
Hgb increase of ≥1.5 g/dL for 8 weeksb 63.0%
(29/46)
5.0%
(1/20)
Weeks 1-24
REBLOZYL
(n=153)
Placebo
(n=76)
Modified hematologic improvement-erythroid (mHI-E) 58.8%
(90/153)
17.1%
(13/76)
RBC transfusion reduction of ≥4 units/8 weeksa 54.2%
(58/107)
21.4%
(12/56)
Hgb increase of ≥1.5 g/dL for 8 weeksb 69.6%
(32/46)
5.0%
(1/20)

aPercentage based on number of patients with baseline RBC transfusion burden of ≥4 units/8 weeks (n=107 in the REBLOZYL arm).
bPercentage based on number of patients with baseline RBC transfusion burden of <4 units/8 weeks (n=46 in the REBLOZYL arm).

Analysis limitations

  • The mHI-E analysis is a broader analysis than the primary endpoint of transfusion independence, and included patients who did not meet the primary endpoint, but2:
    • Achieved transfusion reduction of ≥4 units over 8 weeks (with higher baseline transfusion burden)
    • Achieved an Hgb increase of ≥1.5 g/dL for 8 weeks in the absence of transfusions (with lower baseline transfusion burden)
  • Patients may have experienced multiple periods of response intermittently between periods without response over the 24-week assessment period and extension phase through 25 to 48 weeks2
  • All patients in both arms were eligible to receive BSC, which included RBC transfusions as needed1
  • 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

BSC=best supportive care.

PATIENT OUTCOMES: REBLOZYL EFFICACY

With REBLOZYL, you can now
achieve transfusion independence
AND hematologic improvement1

Study design: REBLOZYL was studied in the pivotal phase 3 MEDALIST trial of 229 patients with IPSS-R very low-, low-, or intermediate-risk MDS who have ring sideroblasts and require RBC transfusions (≥2 RBC units/8 weeks) who were randomized 2:1 to REBLOZYL (n=153) or placebo (n=76). Patients were required to have had an inadequate response to prior treatment with an ESA, be intolerant of ESAs, or be ineligible for ESAs (serum EPO >200 U/L). MEDALIST excluded patients with del(5q) MDS, white blood cell count >13 Gi/L, neutrophils <0.5 Gi/L, platelets <50 Gi/L, or with prior use of a disease-modifying agent for treatment of MDS. REBLOZYL was administered 1 mg/kg subcutaneously every 3 weeks.1

EPO=erythropoietin; ESA=erythropoiesis-stimulating agent; IPSS-R=Revised International Prognostic Scoring System; MDS=myelodysplastic syndromes; RBC=red blood cell.

REBLOZYL was studied in the multicenter, randomized, double-blind, placebo-controlled, phase 3 MEDALIST trial1,2

MEDALIST trial design MEDALIST trial design

*The primary efficacy assessment was conducted after completion of 24 weeks on study drug. Patients with a decrease in transfusion requirement or increase in Hgb could continue on blinded study drug thereafter until unacceptable toxicity, loss of efficacy, or disease progression.

SC=subcutaneous injection.

The MEDALIST trial included patients with very low- to intermediate-risk MDS with ring sideroblasts1,3,4

Demographic and disease characteristics REBLOZYL
(n=153)
Placebo
(n=76)
Age, years
Median (min, max) 71.0 (40, 95) 72.0 (26, 91)
Time since original MDS diagnosis,a months
Median (min, max) 44.0 (3, 421) 36.1 (4, 193)
Serum EPO (U/L) categories,b n (%)
<200
200 to 500
>500
Missing
88 (57.5)
43 (28.1)
21 (13.7)
1 (0.7)
50 (65.8)
15 (19.7)
11 (14.5)
0
RBC transfusion/8 weeks over 16 weeks, n (%)
<4 units
≥4 and <6 units
≥6 units
46 (30.1)
41 (26.8)
66 (43.1)
20 (26.3)
23 (30.3)
33 (43.4)
Diagnosis per WHO 2016 criteria,c n (%)
MDS-RSd
MDS/MPN-RS-T
Othere
135 (88.2)
14 (9.2)
4 (2.6)
65 (85.5)
9 (11.8)
2 (2.6)
SF3B1, n (%)
Mutated
Nonmutated
Missing
138 (93.2)
10 (6.8)
0
64 (86.5)
10 (13.5)
1 (1.3)
IPSS-R classification risk category, n (%)
Very low
Low
Intermediate
High
18 (12)
109 (71)
25 (16)
1 (1)
6 (8)
57 (75)
13 (17)
0

aTime since original MDS diagnosis was defined as the number of months from the date of original diagnosis to the date of informed consent. bBaseline EPO was defined as the highest EPO value within 35 days of the first dose of study drug. cMEDALIST enrolled patients with MDS with ring sideroblasts per the WHO 2008 criteria; however, these data are based on post hoc reclassification of patients by the FDA using the WHO 2016 diagnostic criteria (MDS-RS [n=200; 87.3%], MDS/MPN-RS-T [n=23; 10.0%], and Other [n=6; 2.6%]). dIncludes MDS-RS-MLD and MDS-RS-SLD. eIncludes MDS-EB-1, MDS-EB-2, and MDS-U, which met the criteria for inclusion of ring sideroblasts ≥15% of erythroid precursors in the bone marrow or ≥5% (but <15%) if SF3B1 mutation was present.

*Numbers in callouts are based on the entire clinical trial population.

FDA=Food and Drug Administration; MDS-EB-1=myelodysplastic syndromes with excess blasts (5%-9% in the bone marrow or 2%-4% in the blood); MDS-EB-2=myelodysplastic syndromes with excess blasts (10%-19% in the bone marrow or 5%-19% in the blood); MDS-RS-MLD=MDS with multiple lineage dysplasia and ring sideroblasts; MDS-RS-SLD=MDS with single lineage dysplasia and ring sideroblasts; MDS-U=myelodysplastic syndromes, unclassifiable; WHO=World Health Organization.

Primary endpoint: RBC-TI ≥8 weeks during weeks 1 to 241

REBLOZYL® efficacy graph REBLOZYL® efficacy graph

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

APPROXIMATELY

3X

greater percentage of patients receiving REBLOZYL achieved RBC transfusion independence than placebo

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

60% (35/58)

of responders required at least 1 dose increase to achieve RBC-TI2

REBLOZYL had a significantly higher rate of RBC transfusion independence vs placebo for 12 weeks or more1

Key secondary endpoints: RBC-TI ≥12 weeks1

MEDALIST trial key secondary endpoints graph MEDALIST trial key secondary endpoints graph MEDALIST trial key secondary endpoints graph

*The median (range) duration of treatment was 49 weeks (6-114 weeks) on the REBLOZYL arm and 24 weeks (7-89 weeks) on the placebo arm.

RBC-TI ≥8 weeks during Weeks 1 to 24 by diagnosis and baseline transfusion burden in MEDALIST1

Responders/N % Response (95% CI)
REBLOZYL Placebo REBLOZYL Placebo
WHO 2016 diagnosis
MDS-RS 46/135 8/65 34.1 (26.1, 42.7) 12.3 (5.5, 22.8)
MDS/MPN-RS-T 9/14 2/9 64.3 (35.1, 87.2) 22.2 (2.8, 60.0)
Othera 3/4 0/2 75.0 (19.4, 99.4) 0.0 (0.0, 84.2)
Baseline RBC transfusion burden
2-3 units/8 weeksb 37/46 8/20 80.4 (66.1, 90.6) 40.0 (19.1, 63.9)
4-5 units/8 weeksc 15/41 1/23 36.6 (22.1, 53.1) 4.3 (0.1, 21.9)
≥6 units/8 weeks 6/66 1/33 9.1 (3.4, 18.7) 3.0 (0.1, 15.8)
Responders/N
REBLOZYL Placebo
WHO 2016 diagnosis
MDS-RS 46/135 8/65
MDS/MPN-RS-T 9/14 2/9
Othera 3/4 0/2
Baseline RBC transfusion burden
2-3 units/8 weeksb 37/46 8/20
4-5 units/8 weeksc 15/41 1/23
≥6 units/8 weeks 6/66 1/33
% Response (95% CI)
REBLOZYL Placebo
WHO 2016 diagnosis
MDS-RS 34.1
(26.1, 42.7)
12.3
(5.5, 22.8)
MDS/MPN-RS-T 64.3
(35.1, 87.2)
22.2
(2.8, 60.0)
Othera 75.0
(19.4, 99.4)
0.0
(0.0, 84.2)
Baseline RBC transfusion burden
2-3 units/8 weeksb 80.4
(66.1, 90.6)
40.0
(19.1, 63.9)
4-5 units/8 weeksc 36.6
(22.1, 53.1)
4.3
(0.1, 21.9)
≥6 units/8 weeks 9.1
(3.4, 18.7)
3.0
(0.1, 15.8)

aIncludes MDS-EB-1, MDS-EB-2, and MDS-U. bIncludes patients who received 3.5 units. cIncludes patients who received 5.5 units.

MDS-EB-1=myelodysplastic syndromes with excess blasts (5%-9% in the bone marrow or 2%-4% in the blood); MDS-EB-2=myelodysplastic syndromes with excess blasts (10%-19% in the bone marrow or 5%-19% in the blood); MDS-U=myelodysplastic syndromes, unclassifiable; WHO=World Health Organization.


Additional analysis: Modified hematologic improvement-erythroid (mHI-E) was assessed in patients receiving REBLOZYL2

mHI-E was defined per the IWG criteria as the proportion of patients who met mHI-E criteria sustained over any consecutive 56-day (8-week) period2:

  • For patients with baseline RBC transfusion burden of at least 4 units/8 weeks: response was defined as a reduction in RBC transfusion burden of ≥4 RBC units/8 weeks
  • For patients with baseline RBC transfusion burden of less than 4 units/8 weeks: response was defined as a mean Hgb increase of ≥1.5 g/dL/8 weeks in the absence of transfusions for at least 8 weeks

Hgb=hemoglobin; IWG=International Working Group.


Patients achieving mHI-E in MEDALIST2

Weeks 1-24 Weeks 1-48
REBLOZYL
(n=153)
Placebo
(n=76)
REBLOZYL
(n=153)
Placebo
(n=76)
Modified hematologic improvement-erythroid (mHI-E) 52.9%
(81/153)
11.8%
(9/76)
58.8%
(90/153)
17.1%
(13/76)
RBC transfusion reduction of ≥4 units/8 weeksa 48.6%
(52/107)
14.3%
(8/56)
54.2%
(58/107)
21.4%
(12/56)
Hgb increase of ≥1.5 g/dL for 8 weeksb 63.0%
(29/46)
5.0%
(1/20)
69.6%
(32/46)
5.0%
(1/20)
Weeks 1-24
REBLOZYL
(n=153)
Placebo
(n=76)
Modified hematologic improvement-erythroid (mHI-E) 52.9%
(81/153)
11.8%
(9/76)
RBC transfusion reduction of ≥4 units/8 weeksa 48.6%
(52/107)
14.3%
(8/56)
Hgb increase of ≥1.5 g/dL for 8 weeksb 63.0%
(29/46)
5.0%
(1/20)
Weeks 1-24
REBLOZYL
(n=153)
Placebo
(n=76)
Modified hematologic improvement-erythroid (mHI-E) 58.8%
(90/153)
17.1%
(13/76)
RBC transfusion reduction of ≥4 units/8 weeksa 54.2%
(58/107)
21.4%
(12/56)
Hgb increase of ≥1.5 g/dL for 8 weeksb 69.6%
(32/46)
5.0%
(1/20)

aPercentage based on number of patients with baseline RBC transfusion burden of ≥4 units/8 weeks (n=107 in the REBLOZYL arm).
bPercentage based on number of patients with baseline RBC transfusion burden of <4 units/8 weeks (n=46 in the REBLOZYL arm).

Analysis limitations

  • The mHI-E analysis is a broader analysis than the primary endpoint of transfusion independence, and included patients who did not meet the primary endpoint, but2:
    • Achieved transfusion reduction of ≥4 units over 8 weeks (with higher baseline transfusion burden)
    • Achieved an Hgb increase of ≥1.5 g/dL for 8 weeks in the absence of transfusions (with lower baseline transfusion burden)
  • Patients may have experienced multiple periods of response intermittently between periods without response over the 24-week assessment period and extension phase through 25 to 48 weeks2
  • All patients in both arms were eligible to receive BSC, which included RBC transfusions as needed1
  • 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

BSC=best supportive care.

References: 1. REBLOZYL [US Prescribing Information]. Summit, NJ: Celgene Corporation; 2022. 2. Data on file. Celgene Corporation. Summit, New Jersey. 3. Fenaux P, Platzbecker U, Mufti GJ, et al. Luspatercept in patients with lower-risk myelodysplastic syndromes. N Engl J Med. 2020;382(2):140-151. 4. Fenaux P, Platzbecker U, Mufti GJ, et al. Luspatercept in patients with lower-risk myelodysplastic syndromes. N Engl J Med. 2020;382(suppl):1-37.