CLINICAL TRIALS PROFILE FOR REBLOZYL

All Clinical Trials for REBLOZYL

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT04064060 ↗	A Study to Evaluate Long-term Safety in Subjects Who Have Participated in Other Luspatercept (ACE-536) Clinical Trials	Recruiting	Celgene	Phase 3	2019-08-12	A Phase 3b, open-label, single-arm, rollover study to evaluate the long-term safety of luspatercept, to the following subjects: - Subjects receiving luspatercept on a parent protocol at the time of their transition to the rollover study, who tolerate the protocol-prescribed regimen in the parent trial and, in the opinion of the investigator, may derive clinical benefit in the opinion of the investigator from continuing treatment with luspatercept. - Placebo arm subjects from parent protocol (at the time of unblinding or in follow-up) crossing over to luspatercept treatment (provided subjects have met all requirements for entering the rollover study as per the parent protocol). - Subjects in the follow-up phase previously treated with luspatercept or placebo in the parent protocol will continue into long-term post-treatment follow-up in the rollover study until the follow-up commitments are met (unless they meet requirements as per parent protocol to cross-over to luspatercept treatment). The study design is divided into the Transition Phase, Treatment Phase and Follow-up Phase. Subjects will enter transition phase and depending on their background will enter either the treatment phase or the Long-term Post-treatment Follow-up (LTPTFU) phase. - Transition Phase (Screening): up to 21 days prior to enrollment - Treatment Phase: For subjects in luspatercept treatment the dose and schedule of luspatercept in this study will be the same as the last dose and schedule in the parent luspatercept study. For placebo arm subjects from parent protocol (at the time of unblinding or in follow-up) crossing over to luspatercept treatment (provided subjects have met all requirements for entering the rollover study as per the parent protocol) will start at a luspatercept dose of 1.0 mg/kg every 3 weeks (Q3W). This does not apply to subjects that are in long-term follow-up from the parent protocol. - Follow-up Phase: - 42 Day Safety Follow-up Phase: subjects will be followed for 42 days after the last dose of luspatercept, for the assessment of safety-related parameters and adverse event (AE) reporting. - Long-term Post-treatment Follow-up (LTPTFU) Phase: All subjects who are continuing in the LTPTFU Phase, will continue to be followed for 5 years from Dose 1 of the parent protocol, or 3 years of post-treatment from last dose of the parent protocol, whichever occurs later. Subjects will be followed every 6 months until death, withdrawal of consent, study termination, or until a subject is lost to follow-up. Subjects will also be monitored for progression to AML or any malignancies/pre- malignancies. New anticancer or disease related therapies should be collected at the same time schedule. Subjects transitioning from a parent luspatercept study in post-treatment follow-up (safety or LTPTFU) will continue from the same equivalent point in this rollover study. The rollover study will be terminated, and relevant subjects will discontinue from the study when all subjects fulfill 5 years from Dose 1 of the parent protocol, or 3 years of post-treatment from last dose of the parent protocol, whichever occurs later. The shift to commercial drug is an alternative way to stop the study.
NCT04539236 ↗	Luspatercept and Lenalidomide (L2) in Lower-risk, Non-del(5q) MDS Patients	Recruiting	Bristol-Myers Squibb	Phase 1/Phase 2	2021-11-09	The purpose of this study is to evaluate if the combination of drugs, Lenalidomide and Luspatercept, will help improve the treatment of anemia in patients with lower-risk Myelodysplastic Syndrome (MDS).
NCT04539236 ↗	Luspatercept and Lenalidomide (L2) in Lower-risk, Non-del(5q) MDS Patients	Recruiting	Celgene	Phase 1/Phase 2	2021-11-09	The purpose of this study is to evaluate if the combination of drugs, Lenalidomide and Luspatercept, will help improve the treatment of anemia in patients with lower-risk Myelodysplastic Syndrome (MDS).
NCT04539236 ↗	Luspatercept and Lenalidomide (L2) in Lower-risk, Non-del(5q) MDS Patients	Recruiting	Mikkael Sekeres MD	Phase 1/Phase 2	2021-11-09	The purpose of this study is to evaluate if the combination of drugs, Lenalidomide and Luspatercept, will help improve the treatment of anemia in patients with lower-risk Myelodysplastic Syndrome (MDS).
NCT04539236 ↗	Luspatercept and Lenalidomide (L2) in Lower-risk, Non-del(5q) MDS Patients	Recruiting	Mikkael Sekeres, MD	Phase 1/Phase 2	2021-11-09	The purpose of this study is to evaluate if the combination of drugs, Lenalidomide and Luspatercept, will help improve the treatment of anemia in patients with lower-risk Myelodysplastic Syndrome (MDS).

Clinical Trial Conditions for REBLOZYL

Condition Name

Condition Name for REBLOZYL
Intervention	Trials
Myelodysplastic Syndromes	3
Myelodysplastic/Myeloproliferative Neoplasm With Ring Sideroblasts and Thrombocytosis	1
Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable	1
Myeloproliferative Neoplasm(MPN)-Associated Myelofibrosis	1

Condition MeSH

Condition MeSH for REBLOZYL
Intervention	Trials
Myelodysplastic Syndromes	4
Preleukemia	3
Syndrome	2
Myeloproliferative Disorders	2

Clinical Trial Locations for REBLOZYL

Trials by Country

Trials by Country for REBLOZYL
Location	Trials
United States	35
Italy	9
Malaysia	6
Germany	6
Poland	4

Trials by US State

Trials by US State for REBLOZYL
Location	Trials
Ohio	3
New York	3
Massachusetts	3
Florida	3
Texas	2

Clinical Trial Progress for REBLOZYL

Clinical Trial Phase

Clinical Trial Phase for REBLOZYL
Clinical Trial Phase	Trials
Phase 3	3
Phase 2	2
Phase 1/Phase 2	1

Clinical Trial Status

Clinical Trial Status for REBLOZYL
Clinical Trial Phase	Trials
Recruiting	5
Not yet recruiting	1

Clinical Trial Sponsors for REBLOZYL

Sponsor Name

Sponsor Name for REBLOZYL
Sponsor	Trials
Celgene	3
Bristol-Myers Squibb	3
National Cancer Institute (NCI)	1

Sponsor Type

Sponsor Type for REBLOZYL
Sponsor	Trials
Industry	6
Other	4
NIH	1

Clinical Trials Update, Market Analysis, and Projection for REBLOZYL

Last updated: October 27, 2025

Introduction

REBLOZYL (luspatercept-aamt) is a pioneering erythroid maturation agent approved by the FDA in November 2019 for the treatment of anemia in adult patients with beta-thalassemia requiring regular red blood cell (RBC) transfusions, and in March 2020 for anemia in adults with myelodysplastic syndromes (MDS) with ring sideroblasts refractory to or unlikely to respond to erythropoiesis-stimulating agents (ESAs). Developed by Celgene, now part of Bristol Myers Squibb (BMS), REBLOZYL represents a significant advancement in addressing unmet needs for chronic anemias. This report evaluates the latest clinical trial developments and offers a comprehensive market outlook.

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Clinical Trials Overview and Recent Updates

Key Clinical Trials and their Status

1. PERSIST-2 (NCT03342404):

• Objective: Evaluate REBLOZYL’s efficacy and safety in lower-risk MDS patients, independent of ring sideroblast status.
• Status: Completed Phase 2 trial in 2022 demonstrated promising hematologic improvement with manageable safety. Results indicated increased hemoglobin levels, reduced transfusion burden, and durable responses. The trial’s positive outcome catalyzed plans for larger efficacy studies.

2. BEYOND (NCT04224744):

• Objective: Assess REBLOZYL in non-transfusion-dependent thalassemia (NTDT). This is a pivotal trial aimed at expanding indications into NTDT, where anemia management is a critical unmet need.
• Status: Ongoing Phase 3; initial interim data expected by mid-2023. Early signs include improved hemoglobin levels and reduced transfusion requirements, hinting at broadening of therapeutic scope.

3. REBLOZYL in Pediatric Populations:

• Investigational Study: Pathways to pediatric indications are underway, with Phase 2 trials initiated for adolescent beta-thalassemia and MDS, emphasizing long-term safety and efficacy.

Regulatory and Development Pipeline

Bristol Myers Squibb continues to expand REBLOZYL’s label through Phase 3 trials, targeting both MDS and thalassemia. The company's strategic intent is to demonstrate efficacy across broader patient groups and refine dosing regimens. The regulatory pathway for NTDT is promising, with potential supplemental indications submitted upon interim trial success.

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Market Analysis

Current Landscape and Competitive Dynamics

1. Market Size and Composition

• Beta-thalassemia: Estimated to affect approximately 20,000 patients in the U.S. and Europe combined, with a significant proportion requiring regular transfusions.[1]
• MDS: An estimated 60,000 newly diagnosed cases annually in the U.S., with a sizable subset refractory to ESAs requiring alternative therapies.[2]
• NTDT: Approximately 5,000–7,000 patients in the U.S., with growing recognition of unmet therapeutic needs.

2. Existing Treatment Paradigms

• Standard care involves chronic transfusions and iron chelation, with limited options to stimulate erythropoiesis effectively.
• ESAs are often ineffective in many MDS cases or in advanced beta-thalassemia.
• Some patients are dependent on transfusions, increasing the risk for iron overload and reducing quality of life.

Market Penetration and Commercial Strategy

Bristol Myers Squibb’s positioning leverages its established global infrastructure and strong hematology portfolio. REBLOZYL’s approval for transfusion-dependent beta-thalassemia provides a significant foothold, with growth driven by expanding indications and adoption within clinical guidelines. A key strategy includes direct engagement with hematologists and comprehensive education regarding safety and efficacy data.

Challenges include competition from emerging agents such as luspatercept’s close analogs and gene therapy options that aim to cure rather than manage anemia. However, REBLOZYL’s demonstrated safety and convenience position it favorably, especially for patients unsuitable for gene therapy.

Market Projection (2023–2030)

1. Revenue Forecasts

• 2023: Estimated at $250–300 million, driven by initial uptake for beta-thalassemia and MDS.
• 2025: Projected to reach $600–800 million, as NTDT indications commence commercialization and prescriber awareness grows.
• 2030: Potential to surpass $1.5 billion, contingent on successful registration in additional indications and geographic expansion, notably into emerging markets.

2. Growth Drivers

• Increasing prevalence of beta-thalassemia and MDS.
• Broadened regulatory approvals, including potential labeling updates for NTDT.
• Real-world evidence demonstrating safety and efficacy, motivating guideline incorporation.
• Competitive pricing strategies and reimbursement support.

3. Market Risks

• Competitive developments from alternative therapies, including gene editing and other erythropoiesis-stimulating agents.
• Regulatory delays or unfavorable safety profiles emerging in late-stage trials.
• Limited acceptance in regions with conservative formulary policies.

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Conclusion

REBLOZYL stands at a pivotal juncture, with ongoing trials poised to expand its therapeutic scope into NTDT and other anemia-related conditions. Clinical data suggest sustained efficacy in transfusion-dependent patients with a manageable safety profile. Market forecasts are optimistic, driven by significant unmet needs in hemolytic and myelodysplastic anemias, alongside growing global healthcare burdens.

Continued investment in clinical development, strategic regulatory engagement, and targeted commercial expansion are crucial for realizing REBLOZYL’s full market potential. As evidence accrues, REBLOZYL could solidify its position as a cornerstone therapy in the anemia management landscape, with long-term revenues exceeding traditional expectations.

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Key Takeaways

• Clinical Developments: Ongoing Phase 3 trials and interim data indicate REBLOZYL’s potential in treating NTDT and non-transfusion-dependent anemia, promising to broaden its approved patient base.
• Market Opportunities: The global anemia treatment market is expanding, with an estimated value surpassing $3 billion by 2025. REBLOZYL’s targeted indications and favorable profile position it for substantial market share growth.
• Competitive Edge: Its unique mechanism of action and accruing clinical evidence provide a competitive advantage over conventional therapies.
• Growth Outlook: Revenues could reach nearly $1.5 billion by 2030, contingent on regulatory success and geographic expansion.
• Strategic Imperatives: Focused clinical trials, effective stakeholder engagement, and proactive regulation are critical for maximizing commercial success.

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FAQs

Q1: What distinguishes REBLOZYL from other erythropoiesis-stimulating agents?
A1: REBLOZYL (luspatercept) is a fusion protein that enhances late-stage erythroid maturation, offering efficacy in patients unresponsive or intolerant to ESAs, and demonstrates a different mechanism, targeting ineffective erythropoiesis more effectively in certain conditions.

Q2: When is REBLOZYL expected to receive FDA approval for NTDT?
A2: Pending successful interim trial results, FDA filing for NTDT is anticipated in late 2023 or early 2024, with possible approval in 2024–2025.

Q3: What are the primary safety concerns associated with REBLOZYL?
A3: Common adverse effects include hypertension, dizziness, and fatigue. Serious risks involve thromboembolic events, which require monitoring, especially in chronic use.

Q4: How is the market for REBLOZYL expected to evolve globally?
A4: Expansion into European and Asian markets is projected, driven by regulatory approvals and unmet needs. Local pricing, reimbursement, and disease prevalence will influence uptake.

Q5: Will gene therapy impact REBLOZYL’s market share?
A5: Gene therapies aim for cures; however, high costs, limited access, and safety concerns favor the continued role of REBLOZYL in managing anemia, especially in non-eligible patients for gene therapy.

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References

1. [1] Centers for Disease Control and Prevention. Hemoglobinopathies overview. 2022.
2. [2] National Cancer Institute. Myelodysplastic syndromes: Statistics. 2022.