Image courtesy of NHLBI
The US Food and Drug Administration (FDA) has granted fast track designation to luspatercept for the treatment of patients with transfusion-dependent (TD) or non-transfusion-dependent (NTD) β-thalassemia.
Luspatercept is a modified activin receptor type IIB fusion protein that acts as a ligand trap for members of the transforming growth factor-β (TGF-β) superfamily involved in the late stages of erythropoiesis.
The drug regulates late-stage erythrocyte precursor differentiation and maturation. This mechanism of action is distinct from that of erythropoietin, which stimulates the proliferation of early stage erythrocyte precursor cells.
Luspatercept is currently in phase 2 trials in patients with β-thalassemia and individuals with myelodysplastic syndromes (MDS). Data from the trial in β-thalassemia were presented at the 2014 ASH Annual Meeting, and results from the MDS trial were recently presented at the 13th International Symposium on Myelodysplastic Syndromes.
Acceleron Pharma Inc. and Celgene Corporation are jointly developing luspatercept.
About fast track designation
The FDA’s fast track program is designed to facilitate the development of new drugs that are intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs.
The designation provides pharmaceutical companies with the opportunity for more frequent interaction with the FDA while developing a drug. It also allows a sponsor to submit sections of a biologics license application on a rolling basis, as they are finalized.
“The FDA’s fast track designation for the luspatercept development program recognizes the serious unmet medical needs of patients with β-thalassemia and the potential for luspatercept in this area,” said Jacqualyn A. Fouse, president of hematology/oncology for Celgene.
“Celgene and Acceleron are working diligently to initiate a phase 3 clinical program in 2015 to treat patients with β-thalassemia, and we look forward to continuing to work closely with health authorities and other important stakeholders to advance this program.”
Phase 2 trial in β-thalassemia
At ASH 2014, researchers presented results of a phase 2 trial in which they investigated whether luspatercept could increase hemoglobin levels and decrease transfusion dependence.
The goal was to increase hemoglobin levels 1.5 g/dL or more for at least 2 weeks in NTD patients and decrease the transfusion burden by 20% or more over 12 weeks in TD patients.
Thirty patients, 7 TD and 23 NTD, received an injection of luspatercept every 3 weeks for 3 months at doses ranging from 0.2 mg/kg to 1.0 mg/kg.
Three-quarters of patients who received 0.8 mg/kg to 1.0 mg/kg of luspatercept experienced an increase in their hemoglobin levels or a reduction in their transfusion burden.
Of the NTD patients, 8 of 12 with iron overload at baseline experienced a reduction in liver iron concentration of 1 mg or more at 16 weeks.
TD patients had a more than 60% reduction in transfusion burden over 12 weeks. This included 2 patients with β0 β0 genotype, who experienced a 79% and 75% reduction.
Luspatercept did not cause any treatment-related serious or severe adverse events. The most common adverse events were bone pain (20%), headache (17%), myalgia (13%), and asthenia (10%).
There was 1 grade 3 dose-limiting toxicity of worsening lumbar spine bone pain. And 3 patients discontinued treatment early, 1 each with occipital headache, ankle pain, and back pain.
