Luspatercept and sotatercept increased
hemoglobin levels and achieved transfusion independence in patients
with lower risk myelodysplastic syndromes
Celgene Corporation (NASDAQ:CELG) and Acceleron Pharma Inc.
(NASDAQ:XLRN) today announced preliminary data from ongoing phase 2
clinical trials in patients with lower risk myelodysplastic
syndromes (MDS) at the 56th 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.
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 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-β) 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-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 sotatercept, 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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For Celgene:Investors:
908-673-9628investors@celgene.comorMedia:
908-673-2275media@celgene.comorFor
AcceleronInvestors:Acceleron PharmaSteven Ertel,
617-649-9234Chief Business OfficerorMedia:Suda Communications
LLCMaureen L. Suda, 585-387-9248
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