Separate phase III clinical trials show luspatercept to be safe and effective at reducing the need for blood transfusions.
The studies focus on patients with beta thalassemia and myelodysplastic syndromes, respectively.
In the phase III BELIEVE clinical trial, the experimental drug luspatercept significantly reduced the need for blood transfusions in patients with the inherited blood disorder beta thalassemia.
More than 70 percent of patients who received luspatercept were able to cut blood transfusions by at least one-third over any consecutive 12-week period, while just under 30 percent of those who received a placebo were able to achieve the same result.
Beta thalassemia is a genetic blood disorder characterised by reduced production of the protein haemoglobin, which affects the blood’s ability to transport oxygen, and is associated with life-threatening complications such as severe anaemia and organ damage.
Although new treatments have emerged in recent years, including curative gene therapies, blood transfusions remain the standard of care and most accessible treatment for a vast majority of patients.
Many patients require transfusions every few weeks.
Luspatercept is designed to increase the amount of healthy red blood cells by interfering with signals that suppress red blood cell production, thus improving patients’ ability to manufacture their own red blood cells and reducing the need for transfusions.
“Beta thalassemia is a very demanding disease,” said lead study author Maria Domenica Cappellini, of the University of Milan in Italy. “This new approach can totally change the quality of life for the patient. In addition, even for those who don’t become completely transfusion independent, reducing transfusions can reduce associated comorbidities.”
Receiving a blood transfusion carries a small risk of infection or adverse immune reaction.
In addition, patients who require frequent, regular blood transfusions over the course of years often suffer liver and heart problems due to a buildup of iron.
The trial enrolled 336 adult patients with beta thalassemia.
Participants were mostly young, with a median age of 30 years, and required a median of six units of blood over a 12-week period before the trial.
Two-thirds were randomly assigned to receive luspatercept and one-third received a placebo, both administered via an injection every three weeks.
The researchers tracked the number of units of blood each participant required over the course of 48 weeks (about 11 months).
The results show those taking luspatercept were 5.8 times more likely to reach the primary endpoint (a 33% reduction in the number of units of blood needed during the study period) compared with those taking the placebo.
By the final quarter of the trial, about 20 percent of patients overall had cut their number of transfusion units by one-third or more, and 10 percent of patients had cut their transfusion units by half or more.
Reported adverse events included bone pain and thrombotic events, such as stroke, but the rates of these events did not differ significantly between patients taking luspatercept and those taking the placebo.
Genetic variation is known to affect the severity of beta thalassemia, so it may also affect the efficacy of treatments.
The researchers plan to further analyse the data to determine whether genes or other factors affect how patients respond to luspatercept.
Maria Domenica Cappellini, MD, University of Milan, will present this study during an oral presentation session on at ASH 2018 San Diego Convention Centre.
In the phase III MEDALIST clinical trial, the experimental drug luspatercept significantly reduced the need for frequent blood transfusions in just over half (53%) of patients with myelodysplastic syndromes (MDS) who were anaemic, required regular red blood cell transfusions, and showed abnormal iron overload in red blood cell precursors (a condition known as ring sideroblasts) before the study.
Thirty-eight percent of patients who received luspatercept were able to avoid red blood cell transfusions for at least eight weeks.
Myelodysplastic syndromes (MDS) are a type of bone marrow cancer in which the bone marrow fails to manufacture enough healthy blood cells.
Patients with higher-risk forms of the disease often develop bleeding, infections, or acute myeloid leukaemia, a more aggressive type of blood cancer.
Among those with lower-risk MDS, anaemia is the most common subtype of low blood count and causes debilitating symptoms for many patients.
Available anaemia drugs only work for about one-half of patients with lower-risk MDS-related anaemia and about one-quarter of those who are dependent on red blood cell transfusions.
Patients who do not respond to these drugs or have adverse reactions to them may require frequent blood transfusions to boost their supply of red blood cells and haemoglobin, the oxygen-carrying component of blood.
Red blood cell transfusions increase haemoglobin only temporarily, and frequent transfusions are costly and time-consuming.
They can also lead to iron overload, especially in the heart and liver.
“Anemia and the chronic need for transfusions is a very big issue for these patients,” said lead study author Pierre Fenaux, MD, PhD, of Hospital Saint-Louis in Paris. “With low haemoglobin levels, patients are tired all the time and have an increased risk of falls and cardiovascular events. When you can improve haemoglobin levels, you really see a difference in quality of life.”
The trial enrolled 229 adult patients with low, very low, or intermediate-risk MDS with ring sideroblasts.
All patients had either failed to respond to available anaemia drugs or were ineligible for treatment with such drugs, and required red blood cell transfusions at least every one to two months.
Two-thirds were randomly assigned to receive luspatercept and one-third received a placebo, both administered via an injection every three weeks for at least six months
More than one-third (38%) of patients receiving luspatercept and 13 percent of those receiving a placebo achieved the primary endpoint of at least eight weeks without a need for a red blood cell transfusion.
Twenty-eight percent of patients receiving luspatercept and 8 percent of patients receiving a placebo achieved the secondary endpoint of at least 12 weeks without transfusion.
Overall, 53 percent of patients experienced either a significant reduction in the number of transfusions required or an increase in haemoglobin levels even without transfusions, compared with 12 percent of patients receiving placebo.
The most common reported adverse effects with luspatercept treatment included fatigue and muscle pain, though it is difficult to determine whether these effects were related to anaemia or to the drug itself.
It is also unclear whether the drug would offer benefits for patients with higher-risk MDS or those without lower-risk MDS without ring sideroblasts, researchers noted, since only low- and intermediate-risk patients with ring sideroblasts were included in the trial.