On December 5, 2015 Celgene Corporation (NASDAQ:CELG) and Acceleron Pharma Inc. (NASDAQ:XLRN) reported preliminary results from an ongoing long-term Phase 2 extension study in patients with lower risk myelodysplastic syndromes (MDS) at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (Press release, Acceleron Pharma, DEC 5, 2015, View Source [SID:1234508405]). Results highlighted in an oral presentation showed that patients with lower risk MDS treated with luspatercept in the long-term extension study achieved and maintained increased hemoglobin levels and transfusion independence. Celgene and Acceleron are jointly developing luspatercept.
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"These results for longer-term luspatercept treatment in lower risk MDS patients are very exciting," said Aristoteles Giagounidis, M.D., Ph.D., Head of the Department of Oncology, Haematology, and Palliative Care at Marien Hospital in Düsseldorf, Germany. "There is substantial unmet medical need for patients who do not respond or become refractory to treatment with erythropoiesis stimulating agents or who are considered ineligible to receive them. Luspatercept has shown very encouraging activity in these patients which provides the basis for the Phase 3 MEDALIST study."
Luspatercept Data Presented at ASH (Free ASH Whitepaper)
A total of 32 low- or intermediate-1 risk MDS patients were treated with luspatercept in this long-term 24-month open-label extension study. Luspatercept was administered subcutaneously once every 3 weeks at a starting dose level of 1.0 mg/kg. The dose level could be increased to 1.75 mg/kg. Of these 32 patients, 13 had a low transfusion burden ( < 4 units RBC/8 weeks) and 19 had a high transfusion burden (≥4 units RBC/8 weeks). 59% of patients had been treated previously with erythropoiesis stimulating agents (ESA) and 19% of patients had previously been treated with lenalidomide. 91% of the patients were ring sideroblast positive (more than 15% of erythroid cells in the bone marrow were ring sideroblasts).
Patients who were refractory or intolerant to prior ESA treatment
63% (12 of 19) of HTB and LTB patients with prior ESA treatment achieved an International Working Group (IWG) Hematologic Improvement Erythroid (HI-E) response of a reduction of ≥4 units RBC over 8 weeks or a hemoglobin increase ≥1.5 g/dL for ≥8 weeks during their luspatercept treatment period
50% (7 of 14) achieved transfusion independence
Patients who are considered ESA ineligible because they had elevated erythropoietin levels between 200 and 500 U/L
71% (5 of 7) achieved an HI-E response and 50% (2 of 4) achieved transfusion independence
High Transfusion Burden (HTB) Patients
68% (13 of 19) of the HTB patients achieved the IWG HI-E criteria of a reduction of ≥4 units RBC over 8 weeks
42% (8 of 19) of the HTB patients achieved transfusion independence for ≥8 weeks
Low Transfusion Burden (LTB) Patients
69% (9 of 13) of the LTB patients achieved the IWG HI-E response criteria of a hemoglobin increase ≥1.5 g/dL for ≥8 weeks
The mean increase in hemoglobin reached levels between 2.0 and 2.5 g/dL and was maintained for the 9 months for which data are available
Safety
Adverse events at least possibly related to study drug that occurred in patients during the extension study included bone pain, headache, hypotonia, myalgia and nausea. No serious or grade 3 or 4 adverse events related to study drug have been reported during the ongoing extension study.
Celgene and Acceleron are in the process of initiating a global Phase 3 study in low risk, ring sideroblast positive MDS patients.
Luspatercept is an investigational product that is not approved for any use in any country.
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. For more information, please visit www.clinicaltrials.gov.