Anaemia is the most challenging complication of myelodysplastic syndromes (MDS), one of the most common blood cancers, and determining optimal treatment remains an unmet need.

Among several investigational treatments that aim to promote red blood cell (RBC) growth is sotatercept (ACE-011), a drug that has shown efficacy in early studies with healthy volunteers.

This drug, an injectable activin type IIa receptor fusion protein, is designed to attach to a molecule that inhibits erythrocyte (immature RBC) production.

In this Phase II clinical trial, the first study to evaluate sotatercept in MDS patients and seeking to determine the optimal dose of the drug, researchers enrolled 54 largely transfusion-dependent patients who had not responded to treatment with erythrocyte-stimulating agents (ESAs) and other available MDS treatments.

The treatment was administered once every three weeks for four doses, and was continued among responders.

After treatment with the experimental drug, 45 percent of all evaluable patients experienced either a reduced need for transfusions or an increase in haemoglobin levels.

In addition, 19 of the 45 patients who were in the highly transfusion-dependent group prior to receiving sotatercept therapy demonstrated a reduced need for transfusions, including five who became transfusion-independent.

The majority of patients (5 of 8) in the less-transfusion-dependent group prior to sotatercept therapy achieved both transfusion independence and increased haemoglobin levels.

The treatment was generally well tolerated; 37 percent of patients reported one or more treatment-related adverse events.

“This drug shows promise as an agent that may reduce the burden of regular blood transfusions or eliminate this need among anaemic, lower-risk MDS patients,” said lead study author Rami S. Komrokji, MD, of Moffitt Cancer Center in Tampa, FL.

“Importantly, the response rates are more encouraging in our study than most rates reported with other investigational agents. Larger, randomised studies are necessary to confirm these promising results and evaluate whether a higher dose may provide greater benefit without additional toxicity.”

Source: ASH