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REBLOZYL® (luspatercept-aamt) for the Treatment of Anaemia Associated with Beta-Thalassemia

REBLOZYL® (luspatercept-aamt) is a novel erythroid maturation agent (EMA) approved to treat anaemia associated with beta-thalassemia in adult patients who require regular red blood cell (RBC) transfusions.

Drug Name

REBLOZYL® (luspatercept-aamt)

Developer

Celgene and Acceleron Pharma

Current Indication

Anaemia associated with beta-thalassemia

Market Sector

Haematology

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REBLOZYL® (luspatercept-aamt) is a novel erythroid maturation agent (EMA) approved to treat anaemia associated with beta-thalassemia in adult patients who require regular red blood cell (RBC) transfusions.

The biologics license application (BLA) for the drug was accepted and a priority review was granted by the US Food and Drug Administration (FDA) in June 2019. REBLOZYL was approved by the FDA in November 2019.

REBLOZYL is also being evaluated to treat anaemia in adults with myelodysplastic syndromes (MDS) by the FDA and a decision is expected by April 2020. The drug is also under review by the European Medicines Association for beta-thalassemia-associated anaemia or MDA.

REBLOZYL (luspatercept-aamt) is available as an off-white lyophilised powder in a single-dose vial as a subcutaneous injection with an approved dose of 1mg / kg once in 21 days.

Beta thalassemia causes and symptoms

Beta thalassemia is a congenital blood disorder that inhibits the production of haemoglobin. Also known as Cooley’s anaemia, the disorder occurs due to genetic defects that cause abnormalities in haemoglobin structure.

Beta thalassemia is linked to ineffective erythropoiesis, resulting in the production of fewer and unhealthy RBCs, often leading to severe anaemia. The disease is categorised into two types, thalassemia major and intermedia. Thalassemia major is the more serious of the two.

The signs and symptoms of thalassemia intermedia appear in early childhood, within the first two years of life. Typical symptoms include skin yellowing, eye whitening, enlarged spleen, liver, and heart, misshapen bones, delayed puberty, frequent blood transfusions, liver, heart and hormone problems.

REBLOZYL® (luspatercept-aamt) mechanism of action

Luspatercept-aamt is a recombinant fusion protein that binds multiple endogenous Transforming growth factor-beta (TGF-β) superfamily ligands, reducing Smad2 / 3 signalling.

The drug is a first-in-class erythroid maturation agent (EMA) that promotes late-stage erythroid maturation or differentiation of red blood cells.

Clinical trials on REBLOZYL

The US FDA approval of REBLOZYL was based on the results of phase three randomised, placebo-controlled clinical trial named BELIEVE, which compared the safety and efficacy of REBLOZYL® plus best supportive care (BSC) against placebo, plus BSC in adults.

“Luspatercept-aamt is a recombinant fusion protein that binds multiple endogenous Transforming growth factor-beta (TGF-β) superfamily ligands, reducing Smad2 / 3 signalling.”

A total of 336 beta-thalassemia patients who required RBC transfusions were enrolled, of which 112 received a placebo. The patients, who were randomised in 2:1 ratio, received either REBLOZYL or placebo at a starting dose of 1mg / kg via subcutaneous injection for every 21 days up to 48 weeks.

The study was conducted at 65 different locations across 15 countries. Its primary endpoint was a comparison of baseline reduction in RBC transfusion burden in the REBLOZYL arm to the placebo arm.

In the REBLOZYL arm, 21.4% of the patients achieved more than 33% reduction in RBC transfusion burden compared to 4.5% in the placebo group. The secondary endpoint of reduction in transfusion burden of at least 33% was achieved in 19.6% patients in the REBLOZYL group, compared to 3.6% in the placebo group.

The adverse events reported during the trial were thromboembolic events such as deep vein thromboses, pulmonary embolus, and portal vein thrombosis, and ischemic stroke, hypertension and cerebrovascular accident.

Marketing commentary on Celgene

Celgene is a multi-national biopharmaceutical company involved in the development and commercialisation of novel therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation.

Headquartered in New Jersey, US, the company has a portfolio of investigational compounds indicated for multiple myeloma, myelodysplastic syndromes, chronic lymphocytic leukaemia (CLL), non-Hodgkin’s lymphoma (NHL), triple-negative breast cancer and pancreatic cancer.

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