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.
Photos/Multimedia Gallery Available: http://www.businesswire.com/multimedia/home/20141208006111/en/
Copyright Business Wire 2014