Luspatercept Demonstrates Superior Efficacy Over Epoetin Alfa in First-Line Treatment of Lower-Risk MDS with Anemia: Phase 3 COMMANDS Study Results

Results from the Phase 3 COMMANDS study will be presented at the official press conference of the American Society of Clinical Oncology (ASCO) annual meeting. The results show that,ReblozylThe proportion of patients in the group (including all clinically relevant subgroups) who achieved transfusion-free status and increased hemoglobin levels was nearly twice that of the recombinant human erythropoietin group.

Liblaze Demonstrates Sustained Treatment Response, with Median Time Free of Red Blood Cell Transfusion Close to2.5 years, 1 year longer than recombinant human erythropoietin

At the European Hematology Association (More research results will be announced at the EHA Annual Meeting, showingReblozylPatients with various bone marrow proliferative abnormal tumor-related gene mutations all demonstrated clinical benefits.

ShanghaiMay 26, 2023PR Newswire -- Bristol-Myers Squibb today announced for the first time the phase 3 COMMANDS clinical study data. This study is an open-label randomized trial designed to evaluate Luspatercept.^®(Injectable Luspatercept) versus an Erythropoiesis-Stimulating Agent (ESA) - Recombinant Human Erythropoietin (epoetin-α) for the treatment of anemia in Red Blood Cell (RBC) transfusion-dependent adult patients with very low-risk, low-risk, and intermediate-risk myelodysplastic syndromes (MDS) who have not received prior ESA therapy. The study results will be presented at a press conference held during the American Society of Clinical Oncology (ASCO) Annual Meeting on June 2 at 3:00 PM Eastern Daylight Time (Abstract #7003), with additional results to be presented in the Oral Abstract Session at the European Hematology Association (EHA) Annual Meeting's plenary session on June 10 at 2:45 PM Central European Summer Time (Abstract #S102).

"The chief investigator of the study, Dr. Guillermo Garcia-Manero, head of the Department of Myelodysplastic Syndromes at the University of Texas MD Anderson Cancer Center, stated: 'Chronic anemia, low hemoglobin levels, and transfusion dependence are major clinical challenges faced by lower-risk MDS patients. These patients have more than a 50% higher risk of mortality compared to non-transfusion-dependent patients. The COMMANDS study results indicate that, for lower-risk MDS patients who have not received erythropoiesis-stimulating agent treatment, luspatercept shows statistically significant improvements in reducing red blood cell transfusion dependence, increasing hemoglobin levels, and enhancing the durability of treatment response compared to recombinant human erythropoietin. Moreover, it demonstrates equivalent or better efficacy across all subgroups with acceptable safety and tolerability.'"

The primary endpoint of the COMMANDS study was red blood cell transfusion independence for 12 weeks (RBC-TI) with an increase in mean hemoglobin (Hb) levels of ≥1.5 g/dL. Key secondary endpoints included erythroid response (HI-E) for at least 8 weeks during weeks 1-24, RBC-TI ≥ 12 weeks, and transfusion independence for 24 weeks. The enrolled population consisted of patients aged ≥18 years with lower-risk, red blood cell transfusion-dependent MDS. Patients were randomized in a 1:1 ratio to receive subcutaneous injections every 3 weeks.Reblozyl(Starting dose 1.0 mg/kg, titrated to 1.75 mg/kg) or once-weekly recombinant human erythropoietin (starting dose 450 IU/kg, titrated to 1050 IU/kg), with a treatment duration ≥24 weeks.

InCOMMANDS Study Data Presented at the ASCO Conference

As of the interim analysis, receivedReblozylThere were 147 evaluable patients in the treatment group and 154 evaluable patients in the recombinant human erythropoietin treatment group, with median treatment durations of 41.6 weeks and 27 weeks, respectively. The study results showed,ReblozylGroup 58.5% (n=86) of patients reached the primary endpoint of the study, which was to achieve red blood cell transfusion independence for 12 weeks (RBC-TI) with an increase in mean hemoglobin (Hb) levels of ≥1.5 g/dL within the first 24 weeks, compared to 31.2% (n=48) in the recombinant human erythropoietin group (p<0.0001).ReblozylGroup 74.1% (n=109) of patients achieved at least 8 weeks of erythroid response, compared to 51.3% (n=79) in the recombinant human erythropoietin group (p<0.0001).ReblozylPatients treated with [drug name] achieved a more durable treatment response compared to those treated with recombinant human erythropoietin, with a median RBC-TI >12 weeks (from Week 1 to the end of treatment) of 126.6 weeks vs. 77 weeks. Within the first 24 weeks of treatment,ReblozylIn the group, 47.6% (n=70) of patients achieved transfusion independence for 24 weeks, compared to 29.2% (n=45) in the recombinant human erythropoietin group (P=0.0006). Investigators also observed this in clinically relevant subgroups.ReblozylThe benefits brought about showed consistent safety characteristics, and no new safety signals emerged.

COMMANDSResearch——ASCOOral Report Abstract#7003

 Safety

Hematology-Related Treatment Period Adverse Events

Reblozyl

(n=178)

Recombinant Human Erythropoietin

(n=176)

Anemia

9.6 %(17)

9.7 %(17)

Thrombocytopenia

6.2 %(11)

1.7 %(3)

Neutropenia

5.1 %(9)

7.4 %(13)

The Most Common Adverse Events During the Treatment Period

Fatigue

14.6 %(26)

6.8 %(12)

Diarrhea

14.6 %(26)

11.4 %(20)

Peripheral Edema

12.9 %(23)

6.8 %(12)

Efficacy

Reblozyl

(n=147)

Recombinant Human Erythropoietin

(n=154)

Primary Endpoint

Free from Red Blood Cell Transfusion12 weeks (RBC-TI) and average
Hemoglobin (Hb) level increased by ≥1.5 g/dL

58.5 %(86)

31.2 %(48)

p<0.0001

Secondary Endpoint

Erythroid Response(HI-E)≥8 weeks

74.1 %(109)

51.3 %(79)

p<0.0001

24 Weeks Free of Red Blood Cell Transfusion

47.6 %(70)

29.2 %(45)

p=0.0006

RBC-TI ≥ 12 weeks

66.7 %(98)

46.1 %(71)

p=0.0002

Association between efficacy and baseline characteristics

Reblozyl

n/N (%)

Recombinant Human Erythropoietin

n/N (%)

Risk Difference

(95% CI)

Serum Erythropoietin (sEPO）
≤200 U/L

74/118 (62.7%)

44/121 (36.4%)

26.35 (12.78 ~ 38.41)

Serum Erythropoietin (sEPO）
＞200 U/L

12/29 (41.4%)

4/33 (12.1%)

29.26 (6.35 ~ 50.83)

RingStatusSideroblasticRedCell +

70/108 (64.8%)

29/112 (25.9%)

38.92 (25.87 ~ 50.70)

RingStatusSideroblasticRedCell–

16/39 (41.0%)

19/41 (46.3%)

-5.32 (-27.71 ~ 16.74)

SF3B1 Mutation

64/92 (69.6%)

27/88 (30.7%)

38.88 (24.13 ~ 51.91)

NonSF3B1 Mutation

22/53 (41.5%)

20/62 (32.3%)

9.25 (-8.73 ~ 26.87)

InEHAAnnounced at the conferenceCOMMANDSResearch Data

Data to be presented at the European Hematology Association (EHA) Annual Meeting include efficacy and safety results consistent with those announced at ASCO. The data show that, for common MDS gene mutations (SF3B1, SF3B1a, ASXL1, TET2, DNMT3A, EZH2, IDH2, U2AF1),ReblozylThe treatment outcomes are superior to recombinant human erythropoietin, and the likelihood of achieving clinical benefit is higher, regardless of the overall mutation burden.

COMMANDSResearch——EHAOral Report Abstract#S102

Association of MDS-related gene mutations

Reblozyl

n/N

Recombinant Human Erythropoietin

n/N

Risk Difference

95% CI

ASXL 1

15/31

3/29

0.38 (0.17 ~ 0.59)

CBL

0/5

2/5

-0.40 (-0.85 ~ 0.05)

DNMT3A

19/28

11/25

0.24 (-0.02 ~ 0.50)

DTA.SF3B1.n

12/31

12/40

0.09 (-0.14 ~ 0.31)

EZH2

5/10

2/9

0.28 (-0.13 ~ 0.69)

IDH2

3/6

1/5

0.30 (-0.23 ~ 0.83)

RUNX1

1/4

0/9

0.25 (-0.17 ~ 0.67)

SF3B1

64/92

27/90

0.40 (0.26 ~ 0.53)

SF3B1.alpha

41/55

16/55

0.45 (0.29 ~ 0.62)

SF3B1.beta

1/4

0/8

0.25 (-0.18 ~ 0.68)

SRSF2

5/14

2/14

0.21 (-0.10 ~ 0.53)

TET2

30/48

16/53

0.32 (0.14 ~ 0.51)

U2AF1

6/16

4/19

0.16 (-0.14 ~ 0.46)

ReblozylThe supplemental Biologics License Application is currently under priority review by the U.S. Food and Drug Administration for the treatment of anemia in adult patients with very low- to intermediate-risk MDS who may require red blood cell transfusions and have not previously received erythropoiesis-stimulating agent therapy. As per the Prescription Drug User Fee Act (PDUFA), the target action date is August 28, 2023. Additionally, the European Medicines Agency has acceptedReblozylTreat the patientPopulation-basedType II Change Application. Bristol-Myers Squibb is collaborating with Merck globally on Ribociclib.^®The development and commercialization cooperation. In November 2021, Merck acquired Acceleron Pharma, which had previously co-developed Reblozyl with Bristol-Myers Squibb.

"Clinical experience shows that only one-third of low-risk MDS patients respond to erythropoiesis-stimulating agents within 6-18 months, so there is an urgent need for more effective treatment options to address chronic anemia," said Matteo Giovanni Della Porta, principal investigator of the COMMANDS study and head of the Leukemia Unit at Humanitas Cancer Center in Milan, Italy. "In the COMMANDS study, the median duration of red blood cell transfusion independence was nearly a year longer in the luspatercept group than in the recombinant human erythropoietin group. In addition, luspatercept demonstrated safety consistent with its known profile, showing its potential as a first-line therapy for red blood cell transfusion-dependent very low- to intermediate-risk MDS patients."

"Noah Berkowitz, M.D., Ph.D., Senior Vice President, Hematology Development at Bristol-Myers Squibb, said: 'The results presented at the American Society of Clinical Oncology and the European Hematology Association annual meetings further demonstrate,ReblozylShould be used as the initial therapy for anemia in low- to intermediate-risk MDS patients. As a potentially more effective and longer-lasting early treatment option,Reblozyl"Can change the standard treatment pattern for these patients."

About Myelodysplastic Tumors

Myelodysplastic Syndromes (MDS) refer to a group of closely related hematological malignancies characterized by the ineffective production of healthy red blood cells (RBCs), white blood cells, and platelets, which can lead to anemia, as well as frequent or severe infections.^[1],[2]MDS patients with concurrent anemia typically require regular blood transfusions to increase the number of healthy red blood cells in circulation.^[3]Frequent blood transfusions increase the risk of iron overload, transfusion reactions, and infections.^[4]Compared with non-transfusion-dependent patients, the overall survival of transfusion-dependent patients was significantly shortened, partly due to iron overload or more severe bone marrow disease than non-transfusion-dependent patients.^[5]。

About Reblozyl^®(Roxadustat for Injection)

ReblozylIs a globally first-in-class erythroid maturation agent that has been shown to promote late-stage erythrocyte maturation in animal models.^[6]Bristol-Myers Squibb is collaborating with Merck globally on Riblozumab.^®'s development and commercialization collaboration. In November 2021, Merck acquired Acceleron Pharma, which had previously co-developed Reblozyl with Bristol-Myers Squibb. Currently, Reblozyl^®The following indications have been approved globally:

For patients who need immediate correction of anemia,ReblozylCannot replace red blood cell transfusion. In China,ReblozylNot approved for use in non-transfusion-dependent β-thalassemia and myelodysplastic syndrome patients.

[1] Mount Sinai. Myelodysplastic Syndrome. Available at:

https://www.mountsinai.org/care/cancer/services/mds. Accessed March 2023.

[2] Myelodysplastic Syndromes Foundation. What is MDS? Available at:

https://www.cancer.org/cancer/myelodysplastic-syndrome/about/what-is mds.html. Accessed March 2023.

[3] Johns Hopkins Medicine. Myelodysplastic Syndrome. Available at: https://www.hopkinsmedicine.org/kimmel_cancer_center/cancers_we_treat/leukemia_program/myelodysplastic_syndrome.html

[4] Rasel M, Mahboobi SK. Transfusion Iron Overload. PubMed. 2021. Available at:

https://www.ncbi.nlm.nih.gov/books/NBK562146/. Accessed March 2023.

[5] Triantafyllidis I, Ciobanu A, Stanca O, Lupu AR. Prognostic factors in myelodysplastic syndromes. Maedica (Bucur). 2012 Dec;7(4):295-302. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3593279. Accessed March 2023.

[6] Galanello R, Origa R. Beta thalassemia. Orphanet Journal of Rare Diseases.

2010;5(11). Available at: https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-5-11. Accessed March 2023.