Clinical Trials

Date: 2017-05-06

Type of information: Presentation of results at a congress

phase: 2

Announcement: presentation of results at the 14th International Symposium on MDS

Company: Celgene (USA - NJ) Acceleron Pharma (USA - MA)

Product: luspatercept

Action mechanism: fusion protein. 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-?) 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. Luspatercept is being developed as part of the global collaboration between Acceleron and Celgene .

Disease: myelodysplastic syndromes, beta-thalassemia

Therapeutic area: Cancer - Oncology - Rare diseases - Genetic diseases


Trial details:

  • Data from two Phase 2 studies were presented : the base study in which patients received treatment with luspatercept for three months and the long-term extension study in which patients may receive treatment with luspatercept for up to an additional five years. In both the three-month base study and the long-term extension study, lower-risk MDS patients were enrolled and treated with open-label luspatercept, dosed subcutaneously once every three weeks.
  • The outcome measures for the studies included the proportion of patients who had an erythroid response (IWG HI-E) or achieved RBC transfusion independence (RBC-TI). IWG HI-E was defined as hemoglobin increase ? 1.5 g/dL sustained for ? 8 weeks in patients with < 4 units RBC / 8 weeks transfusion burden at baseline and hemoglobin levels below 10 g/dL. For patients with a ? 4 units RBC / 8 weeks transfusion burden at baseline, erythroid response was defined as a reduction of ? 4 units RBC sustained for ? 8 weeks. RBC-TI was defined as no RBC transfusions for ? 8 weeks in patients with a ? 2 units RBC / 8 weeks baseline transfusion burden.

Latest news:

  • • On May 6, 2017, Acceleron Pharma and Celgene  announced preliminary Phase 2 results from the ongoing three-month base and long-term extension studies with luspatercept in patients with lower-risk myelodysplastic syndromes (MDS) at the 14th International Symposium on MDS in Valencia, Spain. In lower-risk, erythropoiesis-stimulating agent (ESA)-naïve MDS patients, 48% (11/23) of patients treated with luspatercept achieved red blood cell transfusion independence (RBC-TI) and 51% (20/39) of patients achieved a clinically meaningful erythroid hematological improvement (HI-E) response per the International Working Group's (IWG) criteria. The response rates were positive in patients treated with luspatercept in both ESA -naïve and prior ESA -treated patients.

IWG HI-E, N=82 n (%)

RBC-TI, N=56 n (%)
ESA-Naïve 20/39 (51%) 11/23 (48%)
Prior ESA 22/43 (51%) 11/33 (33%)
  • In patients with baseline erythropoietin (EPO) levels ? 500 international units per liter (IU/L), RBC-TI and IWG HI-E response rates were positive in both ring sideroblast-positive (RS+) and -negative (RS-) patients.
Baseline EPO (IU/L) RS Status

IWG HI-E, N=82 n (%)

RBC-TI, N=56 n (%)

? 500 RS+ 30/46 (65%) 16/29 (55%)
RS- 6/14 (43%) 4/7 (57%)
> 500 RS+ 5/9 (56%) 2/9 (22%)
RS- 1/11 (9%) 0/9 (0%)
Unknown 0/2 (0%) 0/2 (0%)
  • *Table includes both ESA refractory and ESA naïve patients. Patients treated at dose levels ? 0.75 mg/kg.
  • The majority of adverse events (AEs) were grade 1 or 2. AEs at least possibly related to study drug that occurred in at least 3 patients during the studies were fatigue, headache, hypertension, diarrhea, arthralgia, bone pain, injection site erythema, myalgia, and edema peripheral. Grade 3 non-serious AEs possibly or probably related to study drug were ascites, blast cell count increase, blood bilirubin increase, hypertension, platelet count increase, and pleural effusion. Grade 3 serious AEs possibly or probably related to study drug were general physical health deterioration and myalgia.
  • • On May 2, 2015, Acceleron Pharma, announced preliminary data from the ongoing phase 2 clinical trial of luspatercept in patients with lower risk myelodysplastic syndromes (MDS). The data showed that luspatercept increased hemoglobin levels and enabled many patients to become transfusion independent. The ongoing phase 2 clinical trial is fully enrolled and data from 44 of the 58 patients was available for efficacy analyses. 17 of these 44 patients were enrolled in the expansion cohort, using the planned phase 3 dosing regimen, whose data had not been previously presented. Luspatercept was generally well-tolerated with the majority of adverse events (AE) being mild to moderate (grade 1 or 2). There were two possibly related serious adverse events of muscle pain and worsening of general condition. In the higher dose groups (0.75 to 1.75 mg/kg administered subcutaneously every three weeks): 54% achieved the International Working Group (IWG) hematologic improvement-erythroid (HI-E) threshold of efficacy. 36% of patients who received red blood cell transfusions during the 8 weeks prior to treatment in the study achieved transfusion independence for at least 8 weeks during the study.
  • Ring sideroblasts (RS) are a type of abnormal red blood cell (RBC) precursor cell in the bone marrow. These ring sideroblasts are associated with ineffective erythropoiesis and anemia. When at least 15% of the cells in an MDS patient’s bone marrow are ring sideroblasts, this patient is considered RS positive. At least 30% of all MDS patients are RS positive, and the proportion is likely even greater within the lower risk segment of all MDS patients. In the RS positive patients in the higher dose groups treated with luspatercept, 63% achieved IWG HI-E, 39% achieved transfusion independence
  • The presentation was given  by Uwe Platzbecker, M.D., University Hospital in Dresden, Germany in an oral session titled “Best of Clinical Trials II” at the MDS Foundation 13th International Symposium on MDS.

Is general: Yes