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TMCNet:  Studies Presented at 19th European Hematology Association Annual Congress Evaluate Activin Receptor Ligand Trap Programs in Beta-Thalassemia

[June 14, 2014]

Studies Presented at 19th European Hematology Association Annual Congress Evaluate Activin Receptor Ligand Trap Programs in Beta-Thalassemia

SUMMIT, N.J. & CAMBRIDGE, Mass. --(Business Wire)--

Celgene Corporation (NASDAQ:CELG) and Acceleron Pharma Inc. (NASDAQ:XLRN) today announced interim data from two studies of candidates from the companies' joint development program in beta-thalassemia. The data presented at the 19th European Hematology Association (EHA) annual congress show activity for two programs, sotatercept and ACE-536, in patients with both transfusion dependent and non-transfusion dependent beta-thalassemia. There is currently no drug approved to treat beta-thalassemia. Both sotatercept and ACE-536 have been granted orphan drug designation for beta-thalassemia by the United States Food and Drug Administration (FDA).

Sotatercept

In the first study, which was highlighted as part of the EHA press briefing on June 13, sotatercept, a novel activin type IIA receptor fusion protein, was evaluated in transfusion-dependent (TD) and non-transfusion-dependent (NTD) beta-thalassemia patients.

A total of 32 patients were treated in this dose-finding study in which sotatercept was administered subcutaneously once every 3 weeks at doses of 0.1 (n=8), 0.3 (n=9), 0.5 (n=8), or 0.75 (n=7) mg/kg. Of these patients, 22 were non-transfusion dependent and 10 were transfusion dependent.

The mean baseline hemoglobin level for the NTD patients was 8.7 g/dL (range 6.1-10.7), 8.3 g/dL (range 6.0-9.5), 8.2 g/dL (range 6.4-9.3) and 8.8 g/dL (range 7.9-9.6) in the 0.1, 0.3, 0.5 and 0.75 mg/kg groups, respectively. Among these patients, there was a dose-dependent increase in hemoglobin.

  • The proportion of patients achieving a maximum hemoglobin increase of = 1.0 g/dL above baseline was 0%, 67%, 83% and 100% in the 0.1, 0.3, 0.5, and 0.75 mg/kg dose groups, respectively.
  • The proportion of patients achieving a maximum hemoglobin increase of = 2.0 g/dL above baseline was 0%, 0%, 33% and 50% in the 0.1, 0.3, 0.5 and 0.75 mg/kg dose groups, respectively.

In TD patients, there were dose dependent reductions in transfusion burden.

  • The proportion of patients achieving = 20% reduction in transfusion burden was 0%, 33%, 50% and 67% in the 0.1, 0.3, 0.5, and 0.75 mg/kg dose groups, respectively.
  • The proportion of patients achieving = 50% reduction in transfusion burden was 0%, 0%, 0% and 33% in the 0.1, 0.3, 0.5, and 0.75 mg/kg dose groups, respectively.

Of these 32 patients, 25 remain on treatment, with the longest duration of treatment > 78 weeks (patient still on study). Three treatment-related adverse events of grade 2 or higher occurred, leading to treatment discontinuation. In the 0.1 mg/kg group, one TD patient experienced worsening grade 3 bone pain and one NTD patient experienced grade 2 phlebitis. In the 0.5 mg/kg group, one patient with a history of ventricular extrasystoles experienced a grade 3 adverse event of ventricular extrasystoles.

"Activin receptor ligand traps like sotatercept could potentially offer an important new treatment option for patients with beta-thalassemia," said Prof. John Porter of the Research Department of Haematology, University College London. "Therapies that can increase hemoglobin levels and relieve red-blood cell transfusion burden have significant potential as current options are very limited."

ACE-536

A second study evaluated ACE-536, a novel modified activin type IIB receptor fusion protein, in transfusion-dependent (TD) and non-transfusion dependent (NTD) beta-thalassemia patients.

A total of 24 patients were treated with ACE-536 administered subcutaneously once every 3 weeks at doses of 0.2 (n=6), 0.4 (n=6), 0.6 (n=6), or 0.8 (n=6) mg/kg. Patients were eligible to receive up to 5 doses over the 13 weeks of treatment, and then followed for 8 weeks after their last dose. Of these patients, 20 were non-transfusion dependent and 4 were transfusion dependent.

The mean baseline hemoglobin level for the NTD patients was 8.4 g/dL, 8.4 g/dL, 7.8 g/dL and 8.0 g/dL in the 0.2, 0.4, 0.6 and 0.8 mg/kg groups, respectively. Among these patients, there was a dose-dependent increase in hemoglobin.

  • The proportion of patients achieving a maximum hemoglobin increase of = 1.0 g/dL above baseline was 33%, 67%, 100% and 67% in the 0.2, 0.4, 0.6, and 0.8 mg/kg dose groups, respectively.
  • The proportion of patients achieving a maximum hemoglobin increase of = 2.0 g/dL above baseline was 0%, 0%, 20% and 33% in the 0.2, 0.4, 0.6 and 0.8 mg/kg dose groups, respectively.
<> For the four TD patients (one patient received 0.6 mg/kg and 3 patients received 0.8 mg/kg), all demonstrated reductions in transfusion burden (-78.5%, -66.7%, -66.7% and -69.8%). Furthermore, all four patients demonstrated reductions in serum ferritin levels (-39.7%, -27.5%, -59.5% and -42.7%), a marker of iron overload.


No related serious adverse events have been reported to date in this ongoing study. One patient discontinued early due to a related AE (ankle pain in the 0.8 mg/kg group).

"There is substantial need for a novel approach to treating beta-thalassemia patients and we are very excited by the activity we are seeing in both transfusion dependent and non-transfusion dependent beta-thalassemia patients," 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 ACE-536 phase 2 study.

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 and 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 and healthcare providers have few options for patients.

About ACE-536

ACE-536 is a modified type IIB activin receptor fusion protein that acts as a ligand trap for members in the Transforming Growth Factor-Beta (TGF-ß) superfamily involved in the late stages of erythropoiesis (red blood cell production). ACE-536 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 ACE-536 as part of a global collaboration. ACE-536 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 Sotatercept

Sotatercept is an activin receptor type IIA fusion protein that acts as a ligand trap for members in the Transforming Growth Factor-Beta (TGF-ß) superfamily involved in the late stages of erythropoiesis (red blood cell production). Sotatercept 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 sotatercept as part of a global collaboration. Sotatercept is currently in multiple phase 2 clinical trials. 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-ß) 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. For more information, please visit www.acceleronpharma.com.

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 (News - Alert) @Celgene as well.

Forward-Looking Statements

Acceleron:

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 sotatercept and ACE-536, 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 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 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, 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 Form 10-K which was filed with the Securities and Exchange Commission (SEC (News - Alert)) 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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