New Data from Luspatercept Phase 2 Clinical Trial in Beta-Thalassemia Presented at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition

Luspatercept increased hemoglobin levels, reduced transfusion burden and improved measures of iron overload in beta-thalassemia patients

SUMMIT, N.J. & CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Celgene Corporation (CELG) and Acceleron Pharma Inc. (XLRN) today announced the presentation of preliminary data from the luspatercept phase 2 clinical trial in patients with beta-thalassemia at the 56^th 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.

Forward-Looking Statements

Acceleron:
Cautionary Note on Forward-Looking Statements

This press release includes forward-looking statements about the Company's strategy, future plans and prospects, including statements regarding the development of the Company's compounds, including luspatercept, and the Company's TGF-β superfamily program generally, the timeline for clinical development and regulatory approval of the Company's compounds, the expected timing for the reporting of data from ongoing trials, and the structure of the Company's planned or pending clinical trials. The words "anticipate," "appear," "believe," "estimate," "expect," "intend," "may," "plan," "predict," "project," "target," "potential," "will," "would," "could," "should," "continue," and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Each forward-looking statement is subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statement. Applicable risks and uncertainties include the risks that the Company's cash position will be insufficient to fund operations into the second half of 2017, that preclinical testing of the Company's compounds and preliminary data from clinical trials may not be predictive of the results or success of ongoing or later clinical trials, that data may not be available when we expect it to be, that the Company or its collaboration partner, Celgene, will be unable to successfully complete the clinical development of its compounds, that the development of the Company's compounds will take longer or cost more than planned, that the Company may be delayed in initiating or completing any clinical trials, and that the Company's compounds will not receive regulatory approval or become commercially successful products. Other risks and uncertainties include those identified under the heading "Risk Factors" included in the Company's Annual Report on Form 10-K which was filed with the Securities and Exchange Commission (SEC) on March 17, 2014, and other filings that the Company may make with the SEC in the future. The forward-looking statements contained in this press release reflect the Company's current views with respect to future events, and the Company does not undertake and specifically disclaims any obligation to update any forward-looking statements.

Celgene:
This press release contains forward-looking statements, which are generally statements that are not historical facts. Forward-looking statements can be identified by the words "expects," "anticipates," "believes," "intends," "estimates," "plans," "will," “outlook” and similar expressions. Forward-looking statements are based on management’s current plans, estimates, assumptions and projections, and speak only as of the date they are made. We undertake no obligation to update any forward-looking statement in light of new information or future events, except as otherwise required by law. Forward-looking statements involve inherent risks and uncertainties, most of which are difficult to predict and are generally beyond our control. Actual results or outcomes may differ materially from those implied by the forward-looking statements as a result of the impact of a number of factors, many of which are discussed in more detail in our Annual Report on Form 10-K and our other reports filed with the Securities and Exchange Commission.

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