Luspatercept increased hemoglobin levels, reduced transfusion burden and improved measures of iron overload in beta-thalassemia patients
SUMMIT, NJ & CAMBRIDGE, MA, USA I December 7, 2014 I Celgene Corporation (NASDAQ: CELG) and Acceleron Pharma Inc. (NASDAQ: XLRN) today announced the presentation of preliminary data from the luspatercept phase 2 clinical trial in patients with beta-thalassemia at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition. This presentation was one of four selected by ASH to be highlighted in this morning’s press briefing on emerging anemia treatments. Dr. Antonio Piga will present the full set of data in an oral session, showing that luspatercept increased hemoglobin levels, reduced transfusion burden, and improved measures of iron overload in beta-thalassemia patients. Celgene and Acceleron are jointly developing luspatercept.
“These results in beta-thalassemia are extremely exciting,” said Professor Antonio Piga, M.D., Ph.D., Director of Pediatrics at San Luigi Gonzaga University Hospital in Torino, Italy and coordinating principal investigator of the study. “A therapy that could potentially treat both the anemia and complications of beta-thalassemia, such as iron overload, is unprecedented in this disease and could potentially benefit most patients, regardless of the genetic background.”
In the phase 2 study, luspatercept was evaluated in transfusion-dependent (TD) and non-transfusion-dependent (NTD) beta-thalassemia patients.
A total of 30 patients were treated in the dose escalation stage of this study, in which luspatercept was administered subcutaneously, once every 3 weeks for up to 5 doses (16 weeks) to cohorts of 6 patients each at dose levels of 0.2, 0.4, 0.6, 0.8, or 1.0 mg/kg. Of these 30 patients, 23 were non-transfusion dependent and 7 were transfusion dependent.
Improvement of anemia and transfusion burden:
- 9 of 12 patients (75%) treated with dose levels of 0.8 or 1.0 mg/kg of luspatercept met the study primary endpoint of an erythroid response
- 6 of 6 (100%) transfusion dependent patients achieved a reduction in transfusion burden of at least 60% over a 12 week period
- 3 of 6 (50%) non-transfusion dependent patients had a sustained hemoglobin increase of at least 1.5 g/dL for ≥ 2 weeks
Reduction in iron overload:
- Reductions in liver iron concentration (LIC), a measure of iron overload, were observed in both non-transfusion dependent and transfusion-dependent patients
- In non-transfusion dependent patients with baseline LIC ≥5 mg/g dry weight, 8 of 12 (67%) patients had a reduction in LIC of ≥1 mg/g dry weight in this 16 week study
- In transfusion dependent patients with baseline LIC ≥5 mg/g dry weight, 4 of 5 (80%) patients had reductions in LIC ranging from 0.7 to 4.7 mg/g dry weight
- Transfusion dependent patients also had reductions in serum ferritin, another marker of iron overload, ranging from 12-60%
Improvement in disease complications:
- 2 of 2 patients who presented with persistent leg ulcers, a complication of beta-thalassemia, experienced rapid healing of the ulcers following treatment with luspatercept
The most common adverse events were bone pain, headache, myalgia, asthenia, influenza, macule and pain in extremity. There were no drug-related serious adverse events and no patient developed anti-drug antibodies on treatment. 3 patients discontinued early due to adverse events; 1 patient (0.6 mg/kg) with occipital headache, 1 patient (0.8 mg/kg) with ankle pain, and 1 patient (0.8 mg/kg) with back pain.
About Beta-thalassemia
Beta-thalassemia is an inherited disease involving mutations in the beta globin gene leading to deficient hemoglobin production and serious anemia. In beta-thalassemia patients, there is an over production of red blood cell (RBC) precursors in the bone marrow, often resulting in bone deformities, decreased bone mineral density and bone strength, and pathologic fractures. These abundant RBC precursors fail to properly mature into functional RBCs, which is known as ineffective erythropoiesis. Beyond the severe anemia, many patients also suffer from multiple organ dysfunction, largely due to excess iron deposits, known as “iron overload,” resulting from the ineffective erythropoiesis as well as the repeated RBC transfusions to address the anemia. Iron overload can lead to heart failure, liver fibrosis, and diabetes, among other consequences. Current clinical management for beta-thalassemia includes regular RBC transfusions and daily iron chelation therapy, which is associated with toxicities. There are no drugs approved to treat beta-thalassemia leaving healthcare providers with few options for patients.
About Luspatercept
Luspatercept is a modified activin receptor type IIB fusion protein that acts as a ligand trap for members in the Transforming Growth Factor-Beta (TGF-β) superfamily involved in the late stages of erythropoiesis (red blood cell production). Luspatercept regulates late-stage erythrocyte (red blood cell) precursor cell differentiation and maturation. This mechanism of action is distinct from that of erythropoietin (EPO), which stimulates the proliferation of early-stage erythrocyte precursor cells. Acceleron and Celgene are jointly developing luspatercept as part of a global collaboration. Luspatercept is currently in phase 2 clinical trials in patients with beta-thalassemia and in patients with myelodysplastic syndromes. For more information, please visit www.clinicaltrials.gov.
About Acceleron
Acceleron is a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of novel protein therapeutics for cancer and rare diseases. The company is a leader in understanding the biology of the Transforming Growth Factor-Beta (TGF-β) protein superfamily, a large and diverse group of molecules that are key regulators in the growth and repair of tissues throughout the human body, and in targeting these pathways to develop important new medicines. Acceleron has built a highly productive R&D platform that has generated innovative clinical and preclinical protein therapeutic candidates with novel mechanisms of action. These protein therapeutic candidates have the potential to significantly improve clinical outcomes for patients with cancer and rare diseases.
About Celgene
Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global pharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation. For more information, please visit the Company’s website at www.celgene.com. Follow us on Twitter @Celgene as well.
SOURCE: Celgene
Post Views: 129
Luspatercept increased hemoglobin levels, reduced transfusion burden and improved measures of iron overload in beta-thalassemia patients
SUMMIT, NJ & CAMBRIDGE, MA, USA I December 7, 2014 I Celgene Corporation (NASDAQ: CELG) and Acceleron Pharma Inc. (NASDAQ: XLRN) today announced the presentation of preliminary data from the luspatercept phase 2 clinical trial in patients with beta-thalassemia at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition. This presentation was one of four selected by ASH to be highlighted in this morning’s press briefing on emerging anemia treatments. Dr. Antonio Piga will present the full set of data in an oral session, showing that luspatercept increased hemoglobin levels, reduced transfusion burden, and improved measures of iron overload in beta-thalassemia patients. Celgene and Acceleron are jointly developing luspatercept.
“These results in beta-thalassemia are extremely exciting,” said Professor Antonio Piga, M.D., Ph.D., Director of Pediatrics at San Luigi Gonzaga University Hospital in Torino, Italy and coordinating principal investigator of the study. “A therapy that could potentially treat both the anemia and complications of beta-thalassemia, such as iron overload, is unprecedented in this disease and could potentially benefit most patients, regardless of the genetic background.”
In the phase 2 study, luspatercept was evaluated in transfusion-dependent (TD) and non-transfusion-dependent (NTD) beta-thalassemia patients.
A total of 30 patients were treated in the dose escalation stage of this study, in which luspatercept was administered subcutaneously, once every 3 weeks for up to 5 doses (16 weeks) to cohorts of 6 patients each at dose levels of 0.2, 0.4, 0.6, 0.8, or 1.0 mg/kg. Of these 30 patients, 23 were non-transfusion dependent and 7 were transfusion dependent.
Improvement of anemia and transfusion burden:
- 9 of 12 patients (75%) treated with dose levels of 0.8 or 1.0 mg/kg of luspatercept met the study primary endpoint of an erythroid response
- 6 of 6 (100%) transfusion dependent patients achieved a reduction in transfusion burden of at least 60% over a 12 week period
- 3 of 6 (50%) non-transfusion dependent patients had a sustained hemoglobin increase of at least 1.5 g/dL for ≥ 2 weeks
Reduction in iron overload:
- Reductions in liver iron concentration (LIC), a measure of iron overload, were observed in both non-transfusion dependent and transfusion-dependent patients
- In non-transfusion dependent patients with baseline LIC ≥5 mg/g dry weight, 8 of 12 (67%) patients had a reduction in LIC of ≥1 mg/g dry weight in this 16 week study
- In transfusion dependent patients with baseline LIC ≥5 mg/g dry weight, 4 of 5 (80%) patients had reductions in LIC ranging from 0.7 to 4.7 mg/g dry weight
- Transfusion dependent patients also had reductions in serum ferritin, another marker of iron overload, ranging from 12-60%
Improvement in disease complications:
- 2 of 2 patients who presented with persistent leg ulcers, a complication of beta-thalassemia, experienced rapid healing of the ulcers following treatment with luspatercept
The most common adverse events were bone pain, headache, myalgia, asthenia, influenza, macule and pain in extremity. There were no drug-related serious adverse events and no patient developed anti-drug antibodies on treatment. 3 patients discontinued early due to adverse events; 1 patient (0.6 mg/kg) with occipital headache, 1 patient (0.8 mg/kg) with ankle pain, and 1 patient (0.8 mg/kg) with back pain.
About Beta-thalassemia
Beta-thalassemia is an inherited disease involving mutations in the beta globin gene leading to deficient hemoglobin production and serious anemia. In beta-thalassemia patients, there is an over production of red blood cell (RBC) precursors in the bone marrow, often resulting in bone deformities, decreased bone mineral density and bone strength, and pathologic fractures. These abundant RBC precursors fail to properly mature into functional RBCs, which is known as ineffective erythropoiesis. Beyond the severe anemia, many patients also suffer from multiple organ dysfunction, largely due to excess iron deposits, known as “iron overload,” resulting from the ineffective erythropoiesis as well as the repeated RBC transfusions to address the anemia. Iron overload can lead to heart failure, liver fibrosis, and diabetes, among other consequences. Current clinical management for beta-thalassemia includes regular RBC transfusions and daily iron chelation therapy, which is associated with toxicities. There are no drugs approved to treat beta-thalassemia leaving healthcare providers with few options for patients.
About Luspatercept
Luspatercept is a modified activin receptor type IIB fusion protein that acts as a ligand trap for members in the Transforming Growth Factor-Beta (TGF-β) superfamily involved in the late stages of erythropoiesis (red blood cell production). Luspatercept regulates late-stage erythrocyte (red blood cell) precursor cell differentiation and maturation. This mechanism of action is distinct from that of erythropoietin (EPO), which stimulates the proliferation of early-stage erythrocyte precursor cells. Acceleron and Celgene are jointly developing luspatercept as part of a global collaboration. Luspatercept is currently in phase 2 clinical trials in patients with beta-thalassemia and in patients with myelodysplastic syndromes. For more information, please visit www.clinicaltrials.gov.
About Acceleron
Acceleron is a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of novel protein therapeutics for cancer and rare diseases. The company is a leader in understanding the biology of the Transforming Growth Factor-Beta (TGF-β) protein superfamily, a large and diverse group of molecules that are key regulators in the growth and repair of tissues throughout the human body, and in targeting these pathways to develop important new medicines. Acceleron has built a highly productive R&D platform that has generated innovative clinical and preclinical protein therapeutic candidates with novel mechanisms of action. These protein therapeutic candidates have the potential to significantly improve clinical outcomes for patients with cancer and rare diseases.
About Celgene
Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global pharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation. For more information, please visit the Company’s website at www.celgene.com. Follow us on Twitter @Celgene as well.
SOURCE: Celgene
Post Views: 129
