Epoetin Alfa vs Luspatercept for Myelodysplastic Syndrome

(ELEMENT-MDS Trial)

Recruiting at 285 trial locations

Overseen By BMS Clinical Trials Contact Center www.BMSClinicalTrials.com

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Bristol-Myers Squibb

Disqualifiers: Secondary MDS, AML, Stroke, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 96 weeks

360 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, Epoetin Alfa (a medication that stimulates red blood cell production) and Luspatercept, to determine which is more effective and safer for treating anemia in individuals with myelodysplastic syndrome (MDS). Participants must have MDS classified as very low, low, or intermediate risk and must not require blood transfusions. The trial suits those who have not previously used similar medications and who experience noticeable anemia symptoms, such as fatigue or shortness of breath. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it does mention that participants should not have received more than 2 doses of certain anemia treatments recently.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that luspatercept is generally well-tolerated by patients with lower-risk myelodysplastic syndromes (MDS). Some studies suggest it can effectively replace blood transfusions for treating anemia. However, one study found that about 2.1% of patients experienced serious side effects, including a few fatal cases, though most side effects were mild and manageable.

Epoetin alfa, already approved by the FDA for treating anemia in various conditions, is generally safe. Users might experience side effects like high blood pressure or headaches, but these are usually not severe.

Both treatments have been studied extensively, and research shows they are mostly safe and well-tolerated. Prospective trial participants should discuss any concerns with the research team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for myelodysplastic syndrome because they offer new possibilities beyond the current standard of care, which typically includes blood transfusions and drugs like azacitidine or decitabine. Epoetin Alfa is a form of erythropoietin that stimulates the production of red blood cells, potentially reducing the need for transfusions. On the other hand, Luspatercept works differently by enhancing red blood cell maturation, offering a novel approach to managing anemia in patients. This unique mechanism could provide more effective and sustained relief from anemia compared to existing treatments.

What evidence suggests that this trial's treatments could be effective for anemia in MDS?

This trial will compare Epoetin Alfa with Luspatercept for treating anemia in patients with myelodysplastic syndromes (MDS). Studies have shown that Luspatercept, which participants in this trial may receive, can improve anemia by significantly reducing the need for blood transfusions in people with lower-risk MDS. Epoetin Alfa, another treatment option in this trial, helps the body produce more red blood cells and has effectively managed anemia. Research comparing these treatments shows that both manage anemia effectively, but Luspatercept may better reduce the need for transfusions. Overall, both options hold promise for improving anemia symptoms in people with MDS. ^{1 6 7 8 9}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

This trial is for adults with Myelodysplastic Syndrome (MDS) who have anemia but don't need blood transfusions. They should not have had previous treatments with erythropoiesis-stimulating agents, and their MDS should be classified as very low to intermediate-risk. Participants must also experience moderate symptoms of fatigue or other related issues due to anemia.

Inclusion Criteria

My average hemoglobin level was 9.5 g/dL or less before joining the study.

Participant has a baseline endogenous serum erythropoietin (sEPO) level of ≤ 500 U/L

My MDS is classified as very low, low, or intermediate-risk according to WHO.

Exclusion Criteria

My MDS developed after treatment for another disease.

I have been diagnosed with acute myeloid leukemia (AML).

I have had pure red cell aplasia or antibodies against erythropoietin.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Luspatercept or Epoetin Alfa for the treatment of anemia in MDS

96 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Epoetin Alfa
• Luspatercept

Trial Overview The study compares Luspatercept against Epoetin Alfa in treating anemia caused by MDS in participants who haven't used similar drugs before. It aims to see which drug is more effective and safer for patients who aren't dependent on blood transfusions.

How Is the Trial Designed?

Group I: Luspatercept Experimental Treatment 1 Intervention

Group II: Epoetin Alfa Active Control 1 Intervention

Epoetin Alfa is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Epogen for:

• Anemia associated with chronic kidney disease
• Anemia related to HIV infection
• Anemia in patients with cancer on chemotherapy
• Reduction of allogeneic blood transfusions in surgery patients

Approved in European Union as Eprex for:

• Anemia associated with chronic kidney disease
• Anemia in adult patients with non-myeloid malignancies receiving chemotherapy
• Anemia in HIV-infected patients at risk of transfusion due to chronic disease

Approved in Canada as Eprex for:

• Anemia associated with chronic kidney disease
• Anemia in patients with cancer on chemotherapy
• Anemia in HIV-infected patients

Who Is Running the Clinical Trial?

Bristol-Myers Squibb

Lead Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

In a study of over 1,500 patients with chronic kidney disease receiving epoetin alfa, only one patient tested low-positive for anti-EPO antibodies, indicating a very low prevalence of these antibodies in this population.

The findings suggest that a large-scale screening program for anti-EPO antibodies in patients treated with epoetin alfa is not necessary, as the risk of developing pure red cell aplasia (PRCA) appears to be minimal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A cross-sectional immunosurveillance study of anti-EPO antibody levels in CRF patients receiving epoetin alfa in 5 Ontario Renal Centers. Wu, G., Wadgymar, A., Wong, G., et al.[2019]

The study estimated a mean maintenance dose conversion ratio (DCR) of approximately 330.6 to 375.6 units of epoetin alfa to 1 microgram of darbepoetin alfa in nondialyzed patients with chronic kidney disease, indicating a higher DCR than previously reported.

This research utilized advanced methods to account for the nonproportional dose relationship between the two erythropoiesis-stimulating agents, providing a more accurate basis for economic evaluations in switching treatments for anemia in chronic renal failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Empirical methods to calculate an erythropoiesis-stimulating agent dose conversion ratio in nondialyzed patients with chronic kidney disease. Horowitz, J., Agarwal, A., Huang, F., et al.[2023]

Exenatide long-acting release (ELAR) does not increase the risk of cardiovascular events in patients with type 2 diabetes, showing a pooled rate ratio of 0.99 compared to placebo or active comparators based on 16 trials.

ELAR is associated with a significant reduction in all-cause mortality, with a rate ratio of 0.87, suggesting it may be a safer option for patients with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of exenatide long-acting release on cardiovascular events and mortality in patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Bonora, BM., Avogaro, A., Fadini, GP.[2019]

Eprex, which contains epoetin alfa, has been successfully marketed in France under the name Binocrit, indicating its availability as a treatment option.

This development suggests that Binocrit may provide similar therapeutic benefits as Eprex, potentially improving patient access to this important medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epoetin alfa: biosimilar. Copied, with biosimilar status. [2015]

Anaemia is a common issue in cancer patients that can negatively impact their quality of life and life expectancy, making effective treatment important.

Epoetin alfa and darbepoetin alfa are promising alternatives to blood transfusions for managing anaemia in cancer patients, as they have been effective in treating anaemia in patients with chronic renal failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epoetins and [symbol: see text] darbepoetin alfa in malignant disease. [2015]

In a study of 1005 patients with chemotherapy-related anemia, epoetin alfa (EPO) showed a greater increase in hemoglobin levels compared to darbepoetin alfa (DARB) at 4, 8, and 12 weeks after treatment initiation, indicating EPO may be more effective for early hematologic outcomes.

The study found that 48% of patients treated with EPO experienced a significant early hemoglobin response (≥1 g/dL increase by 4 weeks) compared to 38% of those treated with DARB, suggesting that EPO may provide quicker benefits in managing anemia during chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective observational study of patients with chemotherapy-related anemia receiving erythropoietic agents. Mark, TL., McKenzie, RS., Fastenau, J., et al.[2015]

Aflibercept, a drug that blocks VEGF receptors, was shown to improve overall survival in patients with metastatic colorectal cancer, with a median survival of 13.5 months compared to 12.1 months for those receiving a placebo, based on a study of 1226 patients.

While aflibercept demonstrated efficacy in extending survival, it also had a higher frequency of adverse events compared to placebo, highlighting the importance of monitoring for side effects when using anti-VEGF therapies in combination with chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European Medicines Agency approval summary: Zaltrap for the treatment of patients with oxaliplatin-resistant metastatic colorectal cancer. Stanel, SC., Sjöberg, J., Salmonson, T., et al.[2021]

In a study of 26 patients with refractory diabetic macular edema (DME), ziv-aflibercept treatment led to significant improvements in visual acuity and macular thickness after switching from previous anti-VEGF therapies.

No adverse ocular or systemic side effects were reported, indicating that ziv-aflibercept is a safe option for patients who did not respond to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Ziv-Aflibercept in the Treatment of Refractory Diabetic Macular Edema. Ashraf, M., Kayal, HE., Souka, AAR.[2022]

In a study of 402 patients with diabetic macular edema treated with intravitreal aflibercept (IVT-AFL) over 24 months, treatment-naïve patients showed a significant improvement in best-corrected visual acuity (BCVA) with an average gain of +6.5 letters, indicating the efficacy of IVT-AFL in this group.

Previously treated patients maintained their visual acuity gains, showing that IVT-AFL is effective in preserving vision in those who have already received treatment, with an average of 11.3 to 11.9 injections over the study period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-year outcomes of the APOLLON observational study of intravitreal aflibercept monotherapy in France in patients with diabetic macular edema. Korobelnik, JF., Daien, V., Faure, C., et al.[2022]

Intravitreal aflibercept has emerged as an effective treatment for diabetic macular edema (DME), showing significant improvements in visual acuity in several randomized controlled trials.

Aflibercept's unique mechanism, which includes binding to placental growth factors in addition to VEGF, may provide advantages over other anti-VEGF agents, potentially leading to better outcomes for patients with DME.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal Aflibercept in Diabetic Macular Edema: Long-Term Outcomes. Introini, U., Casalino, G.[2017]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10878180/

Treatment patterns and outcomes with luspatercept in ... Treatment patterns and outcomes with luspatercept in patients with lower‐risk myelodysplastic syndromes: A retrospective US cohort analysis

2. news.bms.com news.bms.com/news/details/2025/Bristol-Myers-Squibb-Announces-Topline-Results-from-Phase-3-INDEPENDENCE-Trial-for-Reblozyl-luspatercept-aamt-in-Adult-Patients-with-Myelofibrosis-Associated-Anemia/default.aspx

Corporate news details “It is promising to see that Reblozyl led to clinically relevant improvement of anemia for patients with myelofibrosis, where patients often ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03682536

NCT03682536 | A Study to Compare the Efficacy and ... The purpose of this study is to determine the effectiveness of luspatercept (ACE-536) compared to epoetin alfa on red blood cell (RBC) transfusion independence.

4. reblozyl.com reblozyl.com/mds/how-reblozyl-works/second-line-results

Second-Line MDS Treatment Results Learn about the second-line treatment results and side effects of REBLOZYL® (luspatercept-aamt) for patients with anemia in myelodysplastic syndromes (MDS).

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.6570

Real-world (RW) outcomes of patients (pts) with lower-risk ... This is the first study assessing RW characteristics and outcomes in pts with LR-MDS receiving 1L LUSPA or ESA after 1L LUSPA approval.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11843707/

Safety and efficacy of luspatercept in treating anemia ... These results support luspatercept as a well-tolerated, efficacious alternative to transfusions for Asian patients with lower-risk MDS, who tend ...

7. reblozylpro.com reblozylpro.com/mds-second-line/safety

REBLOZYL® (luspatercept-aamt) Second Line Safety Among the 242 patients treated with REBLOZYL, 5 (2.1%) had a fatal adverse reaction1; Selected laboratory abnormalities that changed from Grade 0 to 1 at ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03900715

An Efficacy and Safety Study of Luspatercept (ACE-536) for ... The goal of this study is to assess the efficacy, safety and PK of luspatercept in anemic patients who are categorized as International Prognostic Scoring ...

9. nejm.org nejm.org/doi/full/10.1056/NEJMoa1908892

Luspatercept in Patients with Lower-Risk Myelodysplastic ... Luspatercept reduced the severity of anemia in patients with lower-risk myelodysplastic syndromes with ring sideroblasts who had been receiving regular red- ...