Luspatercept reduces need for blood transfusions in beta thalassemia and MDS

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Published: 1 Dec 2018
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Dr Maria Domenica Cappellini - University of Milan, Milan, Italy

Dr Maria Domenica Cappellini gives a press conference at ASH 2018 about two studies which suggest Luspatercept reduces need for blood transfusions in beta thalassemia and MDS.

Read the article about this work here.

Good morning to everybody. I’m going to present the results of the BELIEVE trial of luspatercept in adult beta-thalassemia patients who require regular blood transfusions. Beta-thalassemia is a hereditary haemoglobinopathy due to a deficient or even absent globin chain synthesis leading to ineffective erythropoiesis and anaemia. Currently the standard of care for these patients is a regular blood transfusion or long-life and iron chelation to remove the iron accumulated by transfusion. So at present still there is an unmet need in order to identify new approaches for treating this disorder which is really very demanding. Luspatercept is a first in class erythroid maturation agent under development for the treatment of adult patients with beta-thalassemia or MDS associated anaemia. Luspatercept binds to select TGF-β super-family ligands to reduce the aberrant Smad 2/3 signalling pathway and denounce the late stage erythropoiesis.

The BELIEVE study is a phase III double blind, randomised, placebo-controlled, multi-centre study comparing luspatercept plus best supportive care versus placebo plus best supportive care, as I already said, in adult beta-thalassemia patients regularly transfused. 336 beta-thalassemia patients were enrolled aged more than 18 years, requiring a transfusion and transfusion dependency was defined as at least 6-20 units of blood during the 24 weeks before entering the study. Patients were randomised two to one, those on luspatercept started with the dosage of 1mg/kg plus best standard of care; the dose could be adjusted to 1.25mg/kg. The drug was administered subcutaneously every three weeks. After 48 weeks the study was unblinded and we are at this stage now.

The primary endpoint of the study was to observe a reduction of equal or more than 33% in transfusion burden from baseline with a reduction of equal or more than two units during a fixed period, precisely from week 13 to 24. The key secondary endpoints were, again, the observation of a reduction of equal or more than 33% use of blood from baseline in another fixed period, weeks 37-48, and then a reduction of more than 50%, again, during the two fixed periods. Moreover, as secondary endpoints we looked at the mean change in transfusion burden from baseline at weeks 13-24. There was an additional endpoint which probably is the most relevant and most adherent to real life and it’s the achievement of more than 33% reduction in blood transfusion burden from baseline over any consecutive 12 or 24 weeks over treatment. So this is the rolling in methodology. 65 sites participated in 15 different countries which is important because it is quite representative of the world thalassemia population.

As for the primary endpoint, luspatercept definitely met the primary endpoint, showing a statistically significant reduction in transfusion burden compared to placebo, as you can see here. The same for the secondary and additional endpoints, also all the key secondary endpoints were met – luspatercept showed a statistically significant reduction in transfusion burden compared to placebo.

In terms of safety this population per se is exposed to several events and we may say that any adverse event occurring during the treatment was mild, moderate, manageable, without requiring dose modifications or interruption. No deaths were observed during luspatercept.

So at this point we may conclude that luspatercept showed a statistically significant reduction in transfusion burden compared to placebo at at least 33%, one-third. Luspatercept achieved also a statistically significant reduction in transfusion burden in the other two fixed periods and some patients achieved a reduction of more than 50%. Luspatercept achieved a reduction in transfusion burden across any 12 or 24 week analysis, that’s the most important observation. It’s well tolerated in this population so at this stage we may say that luspatercept is a potential new therapy for adult patients with beta-thalassemia who require regular blood transfusion.