On June 10, 2016 Acceleron Pharma Inc. (NASDAQ:XLRN) and Celgene Corporation (NASDAQ: CELG), reported preliminary results from an ongoing long-term Phase 2 extension study with luspatercept in patients with lower risk myelodysplastic syndromes (MDS) at the 21st Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Copenhagen, Denmark (Press release, Acceleron Pharma, JUN 10, 2016, View Source [SID:1234513176]).

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Results highlighted in an oral presentation showed that 51% of patients with lower risk MDS treated with luspatercept (n=49) achieved increased hemoglobin levels and 35% of patients achieved transfusion independence in the 3-month base study. In the ongoing extension study, 81% (26/32) of patients had increased hemoglobin levels and of the patients eligible for transfusion independence (TI), 50% achieved TI with luspatercept treatment. Luspatercept is being developed as part of the global collaboration between Acceleron and Celgene.

"The results for luspatercept in lower risk MDS patients are increasingly encouraging as we gain longer term safety and efficacy experience with this agent," said Uwe Platzbecker, M.D., Professor of Hematology and Head of the MDS program at the University Hospital in Dresden, Germany. "There is a significant unmet need for new therapies that reduce the number of or eliminate the need for blood transfusions."

Highlights of the Luspatercept MDS Phase 2 Data Presented at EHA (Free EHA Whitepaper)

Study Design

Data from two Phase 2 studies were presented at the conference: the completed dose-escalation study in which patients received treatment with luspatercept for three months and the ongoing long-term extension study in which patients receive treatment with luspatercept for an additional 24 months. In both the 3-month base study and the long-term extension study, high transfusion burden patients (≥ 4 units RBC / 8 weeks) and low transfusion burden patients ( < 4 units RBC / 8 weeks) were enrolled and treated with open-label luspatercept, dosed subcutaneously once every 3 weeks. The primary outcome measure for the 3 month study was the proportion of patients who had an erythroid response. Erythroid response was defined as hemoglobin ≥ 1.5 g/dL from baseline for ≥ 14 days in non-transfusion dependent patients or a reduction of either ≥ 4 units or ≥ 50% of units of RBCs transfused compared to pretreatment in transfusion-dependent patients. The primary outcome for the long-term extension study is to evaluate the long-term safety and tolerability of luspatercept with low or intermediate-1 risk MDS who were previously enrolled in the 3-month study.

Efficacy


Response rate (% of patients)

3-month base study
(n=49, higher dose
levels)

Long-term extension
study
(n=32)
International Working Group Hematologic
Improvement-Erythroid (IWG HI-E)
Response Rate (reduction of ≥4 units RBC / 8
weeks or a hemoglobin increase ≥1.5 g/dL ≥ 8
weeks)
51% (25/49) 81% (26/32)
RBC Transfusion Independence (RBC-TI)
Response Rate (Transfusion free ≥ 8 weeks for
patients with ≥ 2 units RBC / 8 weeks prior to
treatment)
35% (14/40) 50% (11/22)
Duration of RBC-TI Range: 9-80+ weeks

For reference, results presented six months ago at the American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting in December 2015 were as follows:

IWG HI-E response rate was 69% (22/32)
RBC-TI response rate was 50% (11/22)
Duration of RBC-TI ranged from 9 to 50+ weeks
Safety

There were three grade 3 adverse events possibly/probably related to study drug (blast cell count increase, myalgia and worsening of general condition).
Adverse events at least possibly related to study drug that occurred in at least 2 patients during studies were fatigue, bone pain, diarrhea, myalgia, headache, hypertension and injection site erythema.
Luspatercept is an investigational product that is not approved for use in any country.

The MEDALIST Trial, a global Phase 3 study in patients with very low, low, or intermediate risk, MDS with ring sideroblasts who require red blood cell transfusions, is currently enrolling.

The slides from this oral presentation are available on Acceleron’s website (www.acceleronpharma.com) under the Science tab.

Acceleron EHA (Free EHA Whitepaper) Conference Call Information

Acceleron will host a conference call and live webcast from EHA (Free EHA Whitepaper) today at 8:00 a.m. EDT (2:00 p.m. CEST). To participate by teleconference, please dial 877-312-5848 (domestic) or 253-237-1155 (international) and refer to the Acceleron EHA (Free EHA Whitepaper) Congress Review.

To access the live webcast, please select "Events & Presentations" in the Investor section on Acceleron’s website (www.acceleronpharma.com) at least 10 minutes beforehand to ensure time for any downloads that may be required.

An archived webcast recording will be available on the Acceleron website beginning approximately two hours after the event.

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-beta) 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. Acceleron and Celgene are enrolling Phase 3 clinical trials that are designed to evaluate the safety and efficacy of luspatercept in patients with myelodysplastic syndromes (the "MEDALIST" study) and in patients with beta-thalassemia (the "BELIEVE" study). For more information, please visit www.clinicaltrials.gov.