Celgene, Acceleron Pharma Report Prelim. Data from Ongoing Phase 2 Trials in Patients with Lower Risk MDS:: Luspatercept, Sotatercept Increased Hemoglobin Levels

Celgene Corporation

and Acceleron Pharma Inc.

today announced preliminary data from ongoing phase 2 clinical trials in patients with lower risk myelodysplastic syndromes (MDS) at the 56^th American Society of Hematology (ASH) Annual Meeting and Exposition. In his oral presentation, Dr. Uwe Platzbecker showed that patients with lower risk MDS treated with luspatercept achieved increased hemoglobin levels and transfusion independence. In a separate poster presentation, Dr. Rami Komrokji showed that lower risk MDS patients who were treated with sotatercept also achieved increased hemoglobin levels and transfusion independence. Celgene and Acceleron are jointly developing luspatercept and sotatercept. “These results in lower risk MDS patients are very exciting,” said Uwe Platzbecker, M.D., Professor of Hematology and Head of the MDS program at the University Hospital in Dresden, Germany and coordinating principal investigator of the luspatercept PACE-MDS study. “Sotatercept and luspatercept may be useful early in the treatment of lower risk MDS patients, either as the initial treatment for anemia or in patients who do not respond or become refractory to treatment with ESAs. These investigational therapeutics have been very well-tolerated and therefore have the potential to benefit many MDS patients.” Luspatercept Data Presented at ASH In this study, luspatercept was evaluated in patients with low- or intermediate-1 risk MDS. A total of 26 patients were treated in this dose-finding stage of the study in which luspatercept was administered subcutaneously once every 3 weeks for up to 5 doses (16 weeks) at doses of 0.125 (n=3), 0.25 (n=3), 0.5 (n=3), 0.75 (n=6), 1.0 (n=3) 1.33 (n=6), or 1.75 (n=2) mg/kg. Of these 26 patients, 19 had a high transfusion burden (≥4 units RBC/8 weeks) and 7 had a low transfusion burden (<4 units RBC/8 weeks). 54% of patients had been treated previously with erythropoiesis stimulating agents (ESA) and 19% of patients had previously been treated with lenalidomide. Low Transfusion Burden (LTB) Patients: * 4 of 5 (80%) LTB patients treated with doses of 0.75-1.75 mg/kg of luspatercept achieved the primary endpoint of hemoglobin increase ≥1.5 g/dL for ≥2 weeks in this 16 week study * Additionally, 2 of 5 (40%) of LTB patients achieved the International Working Group (IWG) Hematologic Improvement Erythroid (HI-E) response criteria of a hemoglobin increase ≥1.5 g/dL for ≥8 weeks * The mean maximum change for patients treated with luspatercept doses of 0.75. and 1.75 mg/kg was 2.2 and 3.5 g/dL, respectively * All 5 LTB patients treated with luspatercept doses of 0.75-1.75 mg/kg had received prior ESA High Transfusion Burden (HTB) Patients: * 5 of 12 (42%) HTB patients treated with luspatercept doses of 0.75-1.75 mg/kg of achieved IWG HI-E criteria of a reduction of ≥4 units RBC over 8 weeks * 3 of 12 (25%) HTB patients treated with luspatercept doses of 0.75-1.75 mg/kg achieved transfusion independence for ≥8 weeks Emerging markers of response: * As published earlier this year in Nature Medicine, the murine analog of luspatercept, RAP-536, can correct ineffective erythropoiesis in a mouse model of MDS * Splicing factor 3B1 (SF3B1) mutations are seen commonly in MDS patients with ring sideroblasts and are associated with ineffective erythropoiesis * Erythroid response (HI-E, IWG) was achieved in 41% of patients treated at ≥0.75 mg/kg. Erythroid response (HI-E, IWG) was achieved in 67% of patients with ring sideroblasts and SF3B1 mutations The most common adverse events were diarrhea, muscle spasms, bone pain, fatigue, myalgia and nasopharyngitis. There were no drug-related serious adverse events. There was one possibly related grade 3 adverse event of blast cell count increase. Sotatercept Data Presented at ASH A second phase 2 study evaluated sotatercept in patients with low- or intermediate-1 risk MDS. A total of 54 patients were treated in this dose-finding study in which sotatercept was administered subcutaneously once every 3 weeks at doses of 0.1 (n=7), 0.3 (n=6), 0.5 (n=21), and 1.0 (n=20) mg/kg. Of these 54 patients, 46 (85%) had a high transfusion burden (≥4 units RBC/8 weeks) and 8 (15%) had a low transfusion burden (<4 units RBC/8 weeks). 96% of patients had prior ESA, 57% had a prior hypomethylating agent, and 48% had prior lenalidomide. Low Transfusion Burden (LTB) Patients: * 5 (63%) patients achieved a mean hemoglobin increase ≥1.5 g/dL and transfusion independence sustained for ≥ 8 weeks * Duration of transfusion independence ranged from 76 to 233 days * Maximum mean hemoglobin increases ranged from 1.9 to 4.4 g/dL High Transfusion Burden (HTB) Patients: * 19 of 45 HTB patients (42%) achieved IWG HI-E criteria of a reduction ≥4 RBC units/8 weeks * 5 HTB patients (11%) achieved transfusion independence * Duration of transfusion independence ranged from 59 to 345+ days The most common adverse events were fatigue/asthenia, headache, decreased appetite, nausea and dyspnea. 3 of 54 (6%) patients discontinued due to treatment emergent adverse events considered related to sotatercept. 1 patient with grade 2 hemolytic anemia; 1 patient with grade 3 hypertension; and 1 patient with grade 2 muscle weakness in the 0.3, 0.5, and 1.0 mg/kg dose groups, respectively.