At a Glance
- Phase 2 trial (NCT05664737) met primary endpoints: ≥1 g/dL Hb rise in NTD α-thalassemia; ≥50% transfusion reduction in TD cohort.
- Reblozyl targets TGF-β pathway to boost late-stage RBC maturation, addressing ineffective erythropoiesis.
- US approvals cover TD beta-thalassemia anemia and specific MDS subtypes; not for NTD beta-thalassemia.
- Data supports potential expansion to α-thalassemia, especially in China, with congress presentation planned.
Written By: Nikita Chaudhari BPharm
Reviewed By: Pharmacally Editorial Team
Bristol Myers Squibb announced positive top-line results from an ongoing ex-US Phase 2 registrational study (NCT05664737) evaluating Reblozyl® (luspatercept-aamt) versus placebo for anemia in adults with alpha (α)-thalassemia.
This marks the first registrational Phase 2 trial designed specifically for this lifelong condition, which has limited treatment options and risks serious complications like iron overload and organ damage.
Study Design and Key Results
The trial includes non-transfusion-dependent (NTD) and transfusion-dependent (TD) cohorts of adults and adolescents with α-thalassemia, assessing Reblozyl plus best supportive care against placebo.
NTD Cohort Primary Endpoint: Statistically significant and clinically meaningful increase in mean haemoglobin (Hb) levels of ≥1 g/dL from baseline over weeks 13-24, without red blood cell (RBC) transfusions.
TD Cohort Primary Endpoint: ≥50% reduction in RBC transfusion burden (at least 2 units) during any 12-week period from weeks 13-48, compared to the pre-treatment baseline.
Secondary Endpoints: All key ones met, reinforcing efficacy.
Safety aligned with Reblozyl’s established profile in thalassemia. Adolescent cohorts remain ongoing. Data will feature at an upcoming medical congress and inform discussions with China’s Center for Drug Evaluation, targeting high-prevalence regions like China.
Cristian Massacesi, BMS Executive VP and Chief Medical Officer, noted: “These positive data further support the potential of Reblozyl for patients around the world… especially in China, with alpha-Thalassemia.”
About Reblozyl and Its Mechanism
Reblozyl, a first-in-class erythroid maturation agent, promotes late-stage red blood cell production in preclinical models by targeting the TGF-β pathway to reduce ineffective erythropoiesis a core issue in thalassemias.
US Indications
Developed with Merck since 2021, it’s approved in the US for:
Anemia in adults with transfusion-dependent beta-thalassemia; ESA-naïve very low- to intermediate-risk myelodysplastic syndromes (MDS) who may need transfusions; and ESA-failing MDS with ring sideroblasts (MDS-RS) or MDS/MPN-RS-T requiring ≥2 RBC units over 8 weeks.
It is not indicated for non-transfusion-dependent beta-thalassemia or immediate anemia correction.
Safety Profile Highlights
Reblozyl carries boxed warnings and precautions:
Risk | Key Details | Management |
Thrombosis/Thromboembolism (TEE) | 3.6% in beta-thalassemia trials (e.g., DVT, PE); higher in splenectomised patients or those on HRT. | Thromboprophylaxis if high-risk; monitor signs. |
Hypertension | 11.4% overall; Grade 3-4 in 2-9.6%. | Monitor pre-dose; treat with antihypertensives. |
Extramedullary Hematopoietic (EMH) Masses | 3.2-6.3% in thalassemia; spinal compression in ~2%. | Monitor symptoms; discontinue if serious. Risk factors: splenectomy, low baseline Hb. |
Embryo-Fetal Toxicity | Fetal harm in animals. | Effective contraception; avoid in pregnancy. |
Common adverse reactions (≥10%, higher than placebo) include headache, bone pain, arthralgia, fatigue. Full US PI: packageinserts.bms.com/pi/pi_reblozyl.pdf.
Clinical Implications
These results expand Reblozyl’s potential beyond beta-thalassemia and MDS into α-thalassemia, addressing unmet needs in NTD/TD patients. Success could accelerate approvals in China and globally, improving hemoglobin stability and reducing transfusion burdens—key for quality of life.
Reference
Bristol Myers Squibb Announces Positive Top-Line Results from Registrational Phase 2 Study of Luspatercept in Adults with Alpha (α)-Thalassemia, 23 February 2026, Bristol Myers Squibb – Bristol Myers Squibb Announces Positive Top-Line Results from Registrational Phase 2 Study of Luspatercept in Adults with Alpha (α)-Thalassemia
A Study to Determine the Efficacy and Safety of Luspatercept in Adult Participants and to Evaluate the Safety and Pharmacokinetics in and Adolescent Participants With Alpha (α)-Thalassemia, ClinicalTrials.gov ID NCT05664737, https://clinicaltrials.gov/study/NCT05664737
About Writer
Nikita Chaudhari
She is a pharmacy graduate with a keen interest in clinical research, pharmacovigilance, and medical writing, particularly inclined towards publication writing and scientific content development. In her words, she is enthusiastic about scientific documentation and publication writing, aiming to contribute to accurate, ethical, and evidence-based medical communication.