Pivotal phase 3 data demonstrated treatment with investigational
luspatercept resulted in significant reduction of transfusion burden
compared to placebo
Regulatory submissions planned in the United States and Europe in the
first half of 2019
SUMMIT, N.J. & CAMBRIDGE, Mass.--(BUSINESS WIRE)--
Celgene Corporation (NASDAQ: CELG) and Acceleron Pharma Inc. (NASDAQ:
XLRN) today announced results from a pivotal, phase 3 trial (BELIEVE)
evaluating the safety and efficacy of luspatercept for the treatment of
adults with beta-thalassemia-associated anemia who require regular red
blood cell (RBC) transfusions. The data were presented by Maria Domenica
Cappellini, M.D. in an oral session of the 60th American
Society of Hematology (ASH) Annual Meeting and Exposition in San Diego,
CA (Abstract #163).
“Currently, the standard of care to help patients with beta-thalassemia
manage their anemia is regular, lifelong red blood cell transfusions,
which over time can result in iron overload and life-threatening
co-morbidities,” said Professor Cappellini, M.D., Professor of Medicine,
University of Milan - Fondazione IRCCS. “These findings from the BELIEVE
study are exciting because they suggest that luspatercept may help
patients reduce their dependence on red blood cell transfusions.”
BELIEVE met the primary endpoint of erythroid response, defined as a
≥33% reduction in RBC transfusion burden (with a reduction of ≥ 2 units
of RBC) during weeks 13–24 compared to the baseline 12-week interval
prior to randomization. The study also included secondary endpoints that
evaluated the impact of treatment on RBC transfusion burden. Mean change
in transfusion burden from baseline to weeks 13-24 (luspatercept vs.
placebo) was -1.35 RBC units.
RBC Transfusion Burden Reduction of ≥ 33% Response Rates
1
Response Time Interval
|
|
|
Luspatercept
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Placebo
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|
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P-value
|
Weeks 13-24
|
|
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21.4% (48/224)
|
|
|
4.5% (5/112)
|
|
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< 0.0001
|
Weeks 37-48
|
|
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19.6% (44/224)
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3.6% (4/112)
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|
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< 0.0001
|
Any 12 weeks during the entire treatment period
|
|
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70.5% (158/224)
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|
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29.5% (33/112)
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|
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< 0.0001
|
Any 24 weeks during the entire treatment period
|
|
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41.1% (92/224)
|
|
|
2.7% (3/112)
|
|
|
< 0.0001
|
|
|
|
|
|
|
|
|
|
|
RBC Transfusion Burden Reduction of ≥ 50% Response Rates
1
Response Time Interval
|
|
|
Luspatercept
|
|
|
Placebo
|
|
|
P-value
|
Weeks 13-24
|
|
|
7.6% (17/224)
|
|
|
1.8% (2/112)
|
|
|
0.0303
|
Weeks 37-48
|
|
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10.3% (23/224)
|
|
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0.9% (1/112)
|
|
|
0.0017
|
Any 12 weeks during the entire treatment period
|
|
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40.2% (90/224)
|
|
|
6.3% (7/112)
|
|
|
< 0.0001
|
Any 24 weeks during the entire treatment period
|
|
|
16.5% (37/224)
|
|
|
0.9% (1/112)
|
|
|
< 0.0001
|
|
|
|
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|
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1RBC transfusion burden reduction response rates are
calculated versus baseline (i.e., the 12 weeks prior to randomization)
BELIEVE Safety Summary (Safety Population)
Grade 3 or higher treatment-emergent adverse events (TEAEs) were
reported in 29.1% (65/223) of patients receiving luspatercept and 15.6%
(17/109) of patients receiving placebo. Serious adverse events were
reported in 15.2% (34/223) of patients receiving luspatercept and 5.5%
(6/109) of patients receiving placebo. A TEAE of acute cholecystitis
resulted in death in one placebo-treated patient (0.9%). No
luspatercept-treated patients died due to TEAEs.
Grade 3 or 4 TEAEs in at least 1% of patients
in either arm
|
|
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Luspatercept
N= 223
|
|
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Placebo
N= 109
|
Anemia
|
|
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3.1%
|
|
|
0.0%
|
Increased liver iron concentration
|
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2.7%
|
|
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0.9%
|
Hyperuricemia
|
|
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2.7%
|
|
|
0.0%
|
Hypertension
|
|
|
1.8%
|
|
|
0.0%
|
Syncope
|
|
|
1.8%
|
|
|
0.0%
|
Back pain
|
|
|
1.3%
|
|
|
0.9%
|
Bone pain
|
|
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1.3%
|
|
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0.0%
|
Blood uric acid increased
|
|
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1.3%
|
|
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0.0%
|
Increased aspartate aminotransferase
|
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1.3%
|
|
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0.0%
|
Increase alanine aminotransferase
|
|
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0.9%
|
|
|
2.8%
|
Thromboembolic events*
|
|
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0.9%
|
|
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0.0%
|
|
|
|
|
|
|
|
*All grades of thromboembolic events, including DVT, PE, portal vein
thrombosis, ischemic stroke, thrombophlebitis, and superficial phlebitis
were reported in 8 of 223 (3.6%) luspatercept-treated versus 1 of 109
(0.9%) placebo-treated patients
“The BELIEVE results demonstrate the potential of luspatercept to help
adults living with beta-thalassemia better manage their anemia and
reduce their transfusion burden,” said Alise Reicin, M.D., President,
Global Clinical Development for Celgene. “These results further our
understanding of the luspatercept clinical profile, which will continue
to inform our plans to advance this promising investigational therapy.”
“These outcomes of the BELIEVE trial increase our confidence in the
potential of luspatercept to become an important new treatment option
for patients suffering from beta-thalassemia,” said Habib Dable,
President and Chief Executive Officer of Acceleron. “Our focus now is to
work diligently with health authorities to help ensure that this
underserved patient population can gain access to luspatercept as
quickly as possible.”
Luspatercept is not approved in any region for any indication. The
companies are planning regulatory application submissions of
luspatercept in the United States and Europe in the first half of 2019.
About BELIEVE
BELIEVE is a phase 3, randomized, double blind, placebo-controlled
multicenter study comparing luspatercept + best supportive care (BSC)
versus placebo + BSC in adult beta-thalassemia patients who require
regular RBC transfusions. The median age of the patients was 30 years in
both treatment arms. 336 patients were randomized 2:1 to receive either
luspatercept 1.0 mg/kg + BSC (224 patients) or placebo + BSC (112
patients) every 3 weeks for up to 48 weeks. Patients in the luspatercept
+ BSC arm were able to be titrated up to 1.25 mg/kg of luspatercept
every 3 weeks. BSC was defined as RBC transfusions and iron chelation
therapy to maintain each patient’s baseline hemoglobin level. Crossover
to the luspatercept treatment group was allowed after unblinding and
assessment by an independent Data Safety Monitoring committee; patients
receiving luspatercept + BSC will be followed for up to 3 years. The
study was conducted at 65 sites in 15 countries.
About Luspatercept
Luspatercept is a first-in-class erythroid maturation agent (EMA) that
is believed to regulate late-stage red blood cell maturation. Acceleron
and Celgene are jointly developing luspatercept as part of a global
collaboration. Phase 3 clinical trials continue to evaluate the safety
and efficacy of luspatercept in patients with MDS (the MEDALIST trial)
and in patients with beta-thalassemia (the BELIEVE trial). A COMMANDS
phase 3 trial in first-line, lower-risk, MDS patients, the BEYOND phase
2 trial in non-transfusion-dependent beta-thalassemia, and a phase 2
trial in myelofibrosis are ongoing. For more information, please visit www.clinicaltrials.gov.
About Celgene
Celgene Corporation, headquartered in Summit, New Jersey, is an
integrated global biopharmaceutical company engaged primarily in the
discovery, development and commercialization of innovative therapies for
the treatment of cancer and inflammatory diseases through
next-generation solutions in protein homeostasis, immuno-oncology,
epigenetics, immunology and neuro-inflammation. For more information,
please visit www.celgene.com.
Follow Celgene on Social Media: Twitter,
Pinterest,
LinkedIn,
Facebook
and YouTube.
About Acceleron
Acceleron is a Cambridge-based, clinical-stage biopharmaceutical company
dedicated to the discovery, development, and commercialization of
therapeutics to treat serious and rare diseases. The Company's
leadership in the understanding of TGF-beta biology and protein
engineering generates innovative compounds that engage the body's
ability to regulate cellular growth and repair.
Acceleron focuses its research and development efforts in hematologic,
neuromuscular, and pulmonary diseases. In hematology, the Company and
its global collaboration partner, Celgene, are developing luspatercept
for the treatment of chronic anemia in myelodysplastic syndromes,
beta-thalassemia, and myelofibrosis. Acceleron is also advancing its
neuromuscular franchise with two distinct Myostatin+ agents, ACE-083 and
ACE-2494, and a phase 2 pulmonary program with sotatercept in pulmonary
arterial hypertension.
For more information, please visit www.acceleronpharma.com.
Follow Acceleron on Social Media: @AcceleronPharma and LinkedIn.
FORWARD-LOOKING STATEMENTS
This press release contains forward-looking statements within the
meaning of The Private Securities Litigation Reform Act of 1995. Such
forward-looking statements include those regarding the potential
benefits of, and plans relating to the collaboration between Acceleron
and Celgene; the potential of luspatercept as a therapeutic drug; and
the benefit of each company’s strategic plans and focus. The words
“anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,”
“predict,” “project,” “will,” “would,” “could,” “potential,” “possible,”
“hope” and similar expressions are intended to identify forward-looking
statements, although not all forward-looking statements contain these
identifying words. Such statements are subject to numerous important
factors, risks and uncertainties that may cause actual events or results
to differ materially from current expectations and beliefs. For example,
there can be no guarantee that luspatercept will be successfully
developed or complete necessary clinical phases. Forward-looking
statements in this press release could also be affected by risks and
uncertainties relating to a number of other important factors,
including: results of clinical trials, including subsequent analysis of
existing data and new data received from ongoing and future studies; the
content and timing of decisions made by the U.S. FDA and other
regulatory authorities, investigational review boards at clinical trial
sites and publication review bodies; the ability to obtain and maintain
requisite regulatory approvals and to enroll patients in planned
clinical trials; the ability to obtain, maintain and enforce patent and
other intellectual property protection for luspatercept; the ability to
maintain key collaborations; and general economic and market conditions.
These and other risks are described in greater detail under the caption
"Risk Factors" included in each company’s public filings with
the Securities and Exchange Commission. Any forward-looking statements
contained in this press release speak only as of the date hereof, and
neither company has any obligation to update any forward-looking
statements, whether as a result of new information, future events or
otherwise, except as may be required by law.
Hyperlinks are provided as a convenience and for informational
purposes only. Neither Celgene nor Acceleron bears responsibility for
the security or content of external websites or websites outside of
their respective control.
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Celgene Corporation
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ir@celgene.com
or
Media:
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Acceleron Pharma Inc.
Todd James, IRC, (617) 649-9393
Vice
President, Investor Relations and Corporate Communications
or
Candice
Ellis, (617) 649-9226
Manager, Investor Relations and Corporate
Communications
or
Media:
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Director,
Corporate Communications
Source: Celgene Corporation