Initial results from phase 2 study
evaluating an investigational use of luspatercept-aamt in
myelofibrosis-associated anemia showed promising clinical activity
– companies plan to initiate pivotal, phase 3 study called
INDEPENDENCE in 2020
Longer-term follow-up from pivotal phase 3
studies of MEDALIST in MDS-associated anemia and BELIEVE in beta
thalassemia-associated anemia showed patients experiencing
sustained clinical benefit
Bristol-Myers Squibb Company (NYSE: BMY) and Acceleron Pharma
(NASDAQ: XLRN) today announced data evaluating the erythroid
maturation agent (EMA) Reblozyl® (luspatercept-aamt) in patients
with anemia associated with a range of serious and rare blood
diseases were presented at the 2019 ASH Annual Meeting in Orlando,
Fla.
Data from investigational uses of luspatercept-aamt included the
initial results from a phase 2 study in myelofibrosis-associated
anemia. Presentations also included updated results from two
pivotal phase 3 studies presented at last year’s ASH meeting—the
MEDALIST study in adult patients with anemia associated with very
low-, low- and intermediate-risk myelodysplastic syndromes (MDS)
who have ring sideroblasts and require red blood cell (RBC)
transfusions, and the BELIEVE study in adult patients with anemia
associated with beta thalassemia who require regular RBC
transfusions.
“The data presented at ASH this year underscore the role that
Reblozyl, the first and only erythroid maturation agent, plays for
patients with beta thalassemia-associated anemia and may serve in
further investigational uses in myelofibrosis and MDS,” said Samit
Hirawat, M.D., Chief Medical Officer of Bristol-Myers Squibb.
“We’re encouraged to see positive study results from
luspatercept-aamt in patients with myelofibrosis-associated anemia,
including among those receiving concomitant ruxolitinib, as JAK
inhibitors are a mainstay of myelofibrosis symptomatology
management,” said Habib Dable, President and Chief Executive
Officer of Acceleron. “This development, coupled with updated data
showing continued clinical benefit from luspatercept-aamt treatment
in patients with MDS and beta thalassemia, underscores our
confidence in luspatercept-aamt’s potential to address significant
unmet needs among patients with a range of chronic anemias.”
Phase 2 Results in
Myelofibrosis-associated Anemia
Seventy-six patients were enrolled in the phase 2 study in
multiple cohorts of patients including two groups with anemia only
(hemoglobin level equal to or below 9.5 grams per deciliter (g/dL)
in a 12-week period prior to the first dose) and without
concomitant ruxolitinib (Cohort 1; n=22) or with concomitant
ruxolitinib (Cohort 3A; n=14). Two other groups included
transfusion dependent (TD; received 2-4 RBC units per 28 days in
the 12 weeks prior to the date of the first dose) patients without
concomitant ruxolitinib (Cohort 2; n=21) and with concomitant
ruxolitinib (Cohort 3B n=19).
Patients in Cohort 3A or 3B were required to be on a stable dose
of ruxolitinib for at least 16 weeks prior to initiating
luspatercept-aamt. All patients received luspatercept-aamt at a
starting dose of 1 mg/kg subcutaneously in three-week treatment
cycles and dose increases were allowed up to a maximum dose level
of 1.75 mg/kg.
For anemia-only patients (Cohorts 1 and 3A), the primary
endpoint was a hemoglobin (Hb) increase of at least 1.5 g/dL from
baseline for at least 12 consecutive weeks at every assessment
within the first 24 weeks on the study, in the absence of any RBC
transfusions. An additional endpoint was the proportion of patients
achieving a mean Hb increase of at least 1.5 g/dL over any
consecutive 12-week period in absence of RBC transfusions.
As of the clinical data cutoff (August 5, 2019), 14% (3/22) and
21% (3/14) of anemia-only patients met the primary endpoint in
Cohorts 1 and 3A, respectively. Additionally, 18% (4/22) of Cohort
1 and 64% (9/14) of Cohort 3A patients achieved a mean Hb increase
of at least 1.5 g/dL from baseline over any consecutive 12-week
period.
For patients receiving RBC transfusions (Cohorts 2 and 3B), the
primary endpoint was RBC transfusion independence (RBC-TI) for at
least 12 consecutive weeks within the first 24 weeks of the study.
An additional endpoint was the proportion of patients demonstrating
at least a 50% reduction in their transfusion burden from baseline
(minimum 4 RBC units) over at least any consecutive 12-week
period.
In Cohorts 2 and 3B, 10% (2/21) and 32% (6/19) of patients
achieved the primary endpoint, respectively. Additionally, 38%
(8/21) of Cohort 2 and 53% (10/19) of Cohort 3B patients achieved
at least a 50% reduction in RBC transfusion burden from baseline
(minimum 4 RBC units).
Four percent (3/76) of patients had grade 3 or higher
treatment-emergent adverse events (TEAEs). The most commonly
occurring TEAEs of any grade greater than 3% were hypertension
(12%), bone pain (9%) and diarrhea (5%). Treatment discontinuations
as the result of TEAEs occurred in seven (9%) patients. There were
no treatment-related deaths.
As a result of the phase 2 study, Bristol-Myers Squibb and
Acceleron plan to move forward with the pivotal phase 3
INDEPENDENCE study in patients with myelofibrosis-associated anemia
who are being treated with JAK inhibitor therapy and who require
RBC transfusions. The study is expected to open in 2020.
Updated Results from the Phase 3 MEDALIST
Study
In an assessment of efficacy and safety, updated results from
the pivotal phase 3 MEDALIST study of an investigational use of
luspatercept-aamt in patients with IPSS-R very low-, low- or
intermediate-risk MDS with ring sideroblasts who require regular
RBC transfusions were presented. In the study, 229 patients were
randomized 2:1 with 153 patients receiving luspatercept-aamt.
This updated analysis measured the achievement and number of
individual periods of RBC-TI of at least 8 weeks throughout the
course of the study. Additionally, clinical benefit (RBC-TI) of at
least 8 weeks and/or modified hematologic improvement-erythroid
(HI-E) was also assessed, along with the total duration of the
clinical benefit, which was defined as time from achieving clinical
benefit until discontinuation due to loss of benefit, adverse
events or other causes.
In the analysis, the median baseline RBC transfusion burden for
both the luspatercept-aamt and placebo arms was 5 units per 8
weeks.
As of the clinical cutoff (July 1, 2019), 47.7% (73/153) of
luspatercept-aamt patients and 15.8% (12/76) of placebo patients
achieved at least one episode of RBC-TI lasting at least 8 weeks at
any point in the study. Sixty-nine point nine percent (51/73) of
patients who responded to luspatercept-aamt experienced multiple
episodes of at least 8 weeks of RBC-TI at any point, interceded by
occasional transfusions.
The median total duration of clinical benefit was 92.3 weeks for
luspatercept-aamt responders (n=98) and 26.8 weeks for placebo
(n=20), with 26.8% of luspatercept-aamt-treated patients remaining
on treatment. No placebo-treated patients remain on treatment. The
median treatment duration for all RBC-TI responders was 109.1 weeks
for luspatercept-aamt-treated patients and 53.6 weeks for patients
on placebo.
Adverse events (AEs) occurring more frequently with
luspatercept-aamt compared to placebo were fatigue, asthenia and
headache. These occurred during cycles 1-4 and were mainly grade 1
or 2, with the incidence decreasing over time. Progression to acute
myeloid leukemia was similar between the luspatercept-aamt (2%) and
placebo (2.6%) arms.
Updated Results from the BELIEVE
Study
The companies also presented an updated analysis of the pivotal
phase 3 BELIEVE study evaluating luspatercept-aamt in adult
patients with beta thalassemia who require regular RBC
transfusions. In the study, 336 patients were randomized 2:1, with
224 patients receiving luspatercept-aamt.
As of the clinical cutoff (January 7 2019), 45.1% (101/224) of
luspatercept-aamt patients and 2.7% (3/112) of placebo patients had
achieved at least a 33% reduction in RBC transfusion burden over
any 24-week period. Among the luspatercept-aamt patients who had a
response, 73.3% (74/101) had at least 2 separate responses, with
59.4% (60/101) having 3 or more responses.
The median duration of clinical benefit (defined as the time
from first response of at least a 33% reduction in RBC transfusion
over any 24-week interval to discontinuation due to any cause) for
patients who responded to luspatercept-aamt was 76.3 weeks
(24-128.1).
The most commonly observed AEs in the safety population (n=332)
included in luspatercept-aamt and placebo patients, respectively,
bone pain (20.2% vs. 8.3%), arthralgia (21.1% vs. 14.7%) and
dizziness (12.1% vs. 4.6%). These AEs typically occurred early on,
and incidence decreased over time.
The Food and Drug Administration has recently granted approval
of Reblozyl for the treatment of anemia in adult patients with beta
thalassemia who require regular RBC transfusions. Reblozyl is not
indicated for use as a substitute for RBC transfusions in patients
who require immediate correction of anemia.
Reblozyl is currently being reviewed by the FDA for an
indication in patients with MDS, and the agency has set a
Prescription Drug User Fee Act (PDUFA), or target action, date of
April 4, 2020 for completion of the review.
Reblozyl is not approved for use in patients with MDS or
myelofibrosis in any country.
Bristol-Myers Squibb: Advancing Cancer
Research
At Bristol-Myers Squibb, patients are at the center of
everything we do. The goal of our cancer research is to increase
quality, long-term survival and make cure a possibility. We harness
our deep scientific experience, cutting-edge technologies and
discovery platforms to discover, develop and deliver novel
treatments for patients.
Building upon our transformative work and legacy in hematology
and Immuno-Oncology that has changed survival expectations for many
cancers, our researchers are advancing a deep and diverse pipeline
across multiple modalities. In the field of immune cell therapy,
this includes registrational chimeric antigen receptor (CAR) T-cell
agents for numerous diseases, and a growing early-stage pipeline
that expands cell and gene therapy targets, and technologies. We
are developing cancer treatments directed at key biological
pathways using our protein homeostasis platform, a research
capability that has been the basis of our approved therapies for
multiple myeloma and several promising compounds in early to
mid-stage development. Our scientists are targeting different
immune system pathways to address interactions between tumors, the
microenvironment and the immune system to further expand upon the
progress we have made and help more patients respond to treatment.
Combining these approaches is key to delivering new options for the
treatment of cancer and addressing the growing issue of resistance
to immunotherapy. We source innovation internally, and in
collaboration with academia, government, advocacy groups and
biotechnology companies, to help make the promise of
transformational medicines a reality for patients.
About Reblozyl (luspatercept-aamt)
Reblozyl is an erythroid maturation agent (EMA) that promoted
late-stage red blood cell maturation in animal models.
Bristol-Myers Squibb and Acceleron are jointly developing Reblozyl
as part of a global collaboration. It is currently approved in the
U.S. for the treatment of anemia in adult patients with beta
thalassemia who require regular RBC transfusions. Reblozyl is not
indicated for use as a substitute for RBC transfusions in patients
who require immediate correction of anemia. A phase 3 trial
(COMMANDS) in erythroid-stimulating agent-naïve, lower-risk MDS
patients, the BEYOND phase 2 trial in adult patients with
non-transfusion-dependent beta thalassemia, and a phase 2 trial in
myelofibrosis patients are ongoing. For more information, please
visit www.clinicaltrials.gov.
REBLOZYL is indicated for the treatment of anemia in adult
patients with beta thalassemia who require regular red blood cell
(RBC) transfusions.
REBLOZYL is not indicated for use as a substitute for RBC
transfusions in patients who require immediate correction of
anemia.
Important Safety Information
WARNINGS AND PRECAUTIONS Thrombosis/Thromboembolism
Thromboembolic events (TEE) were reported in 8/223 (3.6%)
REBLOZYL-treated patients. TEEs included deep vein thrombosis,
pulmonary embolus, portal vein thrombosis, and ischemic stroke.
Patients with known risk factors for thromboembolism (splenectomy
or concomitant use of hormone replacement therapy) may be at
further increased risk of thromboembolic conditions. Consider
thromboprophylaxis in patients at increased risk of TEE. Monitor
patients for signs and symptoms of thromboembolic events and
institute treatment promptly.
Hypertension
Hypertension was reported in 10.7% (61/571) of REBLOZYL-treated
patients. Across clinical studies, the incidence of Grade 3 to 4
hypertension ranged from 1.8% to 8.6%. In patients with beta
thalassemia with normal baseline blood pressure, 13 (6.2%) patients
developed systolic blood pressure (SBP) >130 mm Hg and 33
(16.6%) patients developed diastolic blood pressure (DBP) >80 mm
Hg. Monitor blood pressure prior to each administration. Manage new
or exacerbations of preexisting hypertension using
anti-hypertensive agents.
Embryo-Fetal Toxicity
REBLOZYL may cause fetal harm when administered to a pregnant
woman. REBLOZYL caused increased post-implantation loss, decreased
litter size, and an increased incidence of skeletal variations in
pregnant rat and rabbit studies. Advise pregnant women of the
potential risk to a fetus. Advise females of reproductive potential
to use effective contraception during treatment and for at least 3
months after the last dose.
ADVERSE REACTIONS
Serious adverse reactions
occurring in 1% of patients included cerebrovascular accident and
deep vein thrombosis. A fatal adverse reaction occurred in 1
patient treated with REBLOZYL who died due to an unconfirmed case
of acute myeloid leukemia (AML).
Most common adverse reactions
(at least 10% for REBLOZYL and 1% more than placebo) were headache
(26% vs 24%), bone pain (20% vs 8%), arthralgia (19% vs 12%),
fatigue (14% vs 13%), cough (14% vs 11%), abdominal pain (14% vs
12%), diarrhea (12% vs 10%) and dizziness (11% vs 5%).
LACTATION
It is not known whether REBLOZYL is excreted into human milk or
absorbed systemically after ingestion by a nursing infant. REBLOZYL
was detected in milk of lactating rats. When a drug is present in
animal milk, it is likely that the drug will be present in human
milk. Because many drugs are excreted in human milk, and because of
the unknown effects of REBLOZYL in infants, a decision should be
made whether to discontinue nursing or to discontinue treatment.
Because of the potential for serious adverse reactions in the
breastfed child, breastfeeding is not recommended during treatment
and for 3 months after the last dose.
Please see full Prescribing Information for
REBLOZYL.
About Bristol-Myers
Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose
mission is to discover, develop and deliver innovative medicines
that help patients prevail over serious diseases. For more
information about Bristol-Myers Squibb, visit us at BMS.com or
follow us on LinkedIn, Twitter, YouTube, Facebook and
Instagram.
About Acceleron
Acceleron is a 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 superfamily 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, Bristol-Myers
Squibb, are co-promoting newly approved Reblozyl®
(luspatercept-aamt) in North America for the treatment of anemia in
adult patients with beta thalassemia who require regular red blood
cell transfusions and developing luspatercept-aamt for the
treatment of chronic anemia in myelodysplastic syndromes and
myelofibrosis. Acceleron is also advancing its neuromuscular
program with ACE-083, a locally-acting Myostatin+ agent in phase 2
development in Charcot-Marie-Tooth disease and is conducting 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.
Cautionary Statement Regarding
Forward-Looking Statements
This press release contains “forward-looking statements” within
the meaning of the Private Securities Litigation Reform Act of 1995
regarding, among other things, the research, development and
commercialization of pharmaceutical products. All statements that
are not statements of historical facts are, or may be deemed to be,
forward-looking statements. Such forward-looking statements are
based on historical performance and current expectations and
projections about our future financial results, goals, plans and
objectives and involve inherent risks, assumptions and
uncertainties, including internal or external factors that could
delay, divert or change any of them in the next several years, that
are difficult to predict, may be beyond our control and could cause
our future financial results, goals, plans and objectives to differ
materially from those expressed in, or implied by, the statements.
These risks, assumptions, uncertainties and other factors include,
among others, that future study results will be consistent with the
results to date, that REBLOZYL (luspatercept-aamt) will be
successfully commercialized for the indication for which it is
currently approved, that Reblozyl may not achieve its primary study
endpoints or receive regulatory approval for the additional
indications described in this release in the currently anticipated
timeline or at all and, if approved, whether such product candidate
for such additional indications described in this release will be
commercially successful. No forward-looking statement can be
guaranteed. Forward-looking statements in this press release should
be evaluated together with the many risks and uncertainties that
affect Bristol-Myers Squibb’s business and market, particularly
those identified in the cautionary statement and risk factors
discussion in Bristol-Myers Squibb’s Annual Report on Form 10-K for
the year ended December 31, 2018, as updated by our subsequent
Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and
other filings with the Securities and Exchange Commission. The
forward-looking statements included in this document are made only
as of the date of this document and except as otherwise required by
applicable law, Bristol-Myers Squibb undertakes no obligation to
publicly update or revise any forward-looking statement, whether as
a result of new information, future events, changed circumstances
or otherwise.
Acceleron Cautionary Statement
Regarding Forward-Looking Statements
This press release contains forward-looking statements about
Acceleron’s strategy, future plans and prospects, including
statements regarding the development and commercialization of
Acceleron’s compounds, the timeline for clinical development and
regulatory approval of Acceleron’s compounds, the expected timing
for reporting of data from ongoing clinical trials, and the
potential of REBLOZYL® (luspatercept-aamt) as a therapeutic drug.
The words "anticipate," "believe," "could," "estimate," "expect,"
"goal," "intend," "may," "plan," "potential," "project," "should,"
"target," "will," "would," and similar expressions are intended to
identify forward-looking statements, although not all
forward-looking statements contain these identifying words.
Actual results could differ materially from those included in
the forward-looking statements due to various factors, risks and
uncertainties, including, but not limited to, that preclinical
testing of Acceleron’s compounds and data from clinical trials may
not be predictive of the results or success of ongoing or later
clinical trials, that the results of any clinical trials may not be
predictive of the results or success of other clinical trials, that
regulatory approval of Acceleron’s compounds in one indication or
country may not be predictive of approval in another indication or
country, that the development of Acceleron’s compounds will take
longer and/or cost more than planned, that Acceleron or its
collaboration partner, BMS, will be unable to successfully complete
the clinical development of Acceleron’s compounds, that Acceleron
or BMS may be delayed in initiating, enrolling or completing any
clinical trials, and that Acceleron’s compounds will not receive
regulatory approval or become commercially successful products.
These and other risks and uncertainties are identified under the
heading “Risk Factors” included in Acceleron’s most recent Annual
Report on Form 10-K, and other filings that Acceleron has made and
may make with the SEC in the future.
The forward-looking statements contained in this press release
are based on management's current views, plans, estimates,
assumptions, and projections with respect to future events, and
Acceleron does not undertake and specifically disclaims any
obligation to update any forward-looking statements.
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Bristol-Myers Squibb Company Media Inquiries:
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Investors: Tim Power 609-252-7509
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Acceleron Pharma Inc. Investors: Todd James, IRC, (617)
649-9393 Vice President, Investor Relations and Corporate
Communications
Ed Joyce, (617) 649-9242 Director, Investor Relations
or
Media: Matt Fearer, (617) 301-9557 Director, Corporate
Communications
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