FDA Grants Priority Review to First-in-Class Anemia Therapy Reblozyl for Non-Transfusion Dependent Beta Thalassemia

Recently, Celgene, a subsidiary of Bristol-Myers Squibb (BMS), announced that the U.S. FDA has granted priority review status to the supplemental Biologics License Application (sBLA) for Reblozyl (luspatercept-aamt), a "first-in-class" erythroid maturation agent, for the treatment of adult patients with non-transfusion-dependent β-thalassemia. Previously, the FDA had approved the drug for treating transfusion-dependent β-thalassemia and anemia associated with certain rare blood disorders. In January this year, China's National Medical Products Administration Center for Drug Evaluation (CDE) also included injectable Reblozyl (Chinese trade name: Lusutrombopag) on its priority review list for treating β-thalassemia patients who require regular red blood cell (RBC) transfusions.

β-Thalassemia is a hereditary blood disorder and one of the most common autosomal recessive genetic diseases. The genetic defect in hemoglobin leads to a progressive reduction in red blood cell (RBC) production, often resulting in severe anemia and other serious health issues. Treatment options for this condition are limited, with frequent RBC transfusions being the primary approach; however, this can lead to iron overload and infections, causing severe complications such as organ damage. Patients with non-transfusion-dependent β-thalassemia, although able to survive without lifelong regular transfusions, still require occasional or intermittent frequent transfusions and face a series of clinical complications due to chronic anemia and iron overload.

Reblozyl is an innovative drug that reduces the transfusion burden by regulating the maturation process of late-stage red blood cells. As a soluble fusion protein, it is composed of the Fc domain of human immunoglobulin G1 (IgG1) fused with the extracellular domain of activin receptor type IIB (ActRIIB). It acts as a ligand trap for TGF-β, preventing the activation of the Smad2/3 signaling pathway, thereby promoting the differentiation and maturation of late-stage red blood cells to alleviate the burden of regular RBC transfusions for patients.

▲Reblozyl can increase the hemoglobin content in patients' blood and promote the differentiation of mature red blood cells (Image Source: reblozyl.com)

This application is based on the positive results obtained from a pivotal Phase 2 clinical trial. The trial enrolled 145 adult patients with non-transfusion-dependent β-thalassemia. On the basis of optimal supportive care, participants were randomized in a 2:1 ratio to receive either Reblozyl or placebo. The trial met its primary endpoint, showing that from week 13 to week 24 of treatment, 74 out of 96 patients (77.1%) in the Reblozyl group had an increase in mean hemoglobin levels of ≥1.0 g/dL from baseline, compared to none in the placebo group (0/49). The drug also demonstrated favorable tolerability and safety profiles. The most common adverse events were bone pain, headache, and arthralgia, with no reports of malignancy or thromboembolic events.

References:

[1] U.S. Food and Drug Administration Accepts for Priority Review supplemental Biologics License Application for Reblozyl® (luspatercept-aamt) in Adults with Non-Transfusion Dependent (NTD) Beta Thalassemia. Retrieved December 3, 2021, from https://www.businesswire.com/news/home/20211202006066/en

[2] Bristol Myers Squibb and Acceleron Present First Results from Phase 2 BEYOND Study of Reblozyl® (luspatercept-aamt) in Adults with Non-Transfusion Dependent(NTD)Beta Thalassemia. Retrieved December 3, 2021, from https://news.bms.com/news/details/2021/Bristol-Myers-Squibb-and-Acceleron-Present-First-Results-from-Phase-2-BEYOND-Study-of-Reblozylluspatercept-aamt-in-Adults-with-Non-Transfusion-DependentNTDBeta-Thalassemia/default.aspx

(Original text has been abridged)

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