Approval of Reblozyl is based on
head-to-head, pivotal Phase 3 COMMANDS study, in which Reblozyl
nearly doubled the percentage of patients achieving transfusion
independence and hemoglobin increase, along with increased
durability compared to epoetin alfa
This is the fourth authorized indication in
Europe for Reblozyl, a first-in-class treatment for patients with
disease-related anemia and the first therapy to demonstrate
superior efficacy vs. epoetin alfa in LR-MDS
Bristol Myers Squibb (NYSE: BMY) today announced that the
European Commission (EC) has expanded approval of Reblozyl®
(luspatercept) to include the first-line treatment of adult
patients with transfusion-dependent anemia due to very low, low and
intermediate-risk myelodysplastic syndromes (MDS). This approval of
Reblozyl covers all EU member states.*
“With this approval for Reblozyl as a first-line treatment for
anemia in adults with lower-risk MDS, more patients in the EU will
have the potential to become transfusion independent for longer
periods of time compared to current options available,” said Monica
Shaw, M.D., senior vice president and head of European Markets,
Bristol Myers Squibb. “This milestone underscores our ongoing
commitment to developing new options for patients with
disease-related anemia.”
The approval is based on the pivotal Phase 3 COMMANDS study, in
which Reblozyl demonstrated superior efficacy compared to epoetin
alfa, an erythropoiesis stimulating agent, in the study’s primary
endpoint of concurrent red blood cell transfusion independence and
hemoglobin increase. Safety results were consistent with previous
MDS studies and were in line with expected symptoms in this patient
population. Reblozyl is also approved in the United States and
Japan for the first-line treatment of anemia associated with
lower-risk MDS.
“In the treatment of lower-risk MDS, few patients experience a
lasting response to erythroid stimulating agents, leaving a
critical need for more effective treatment options to address the
burden of their anemia,” said Matteo Giovanni Della Porta, M.D.,
study investigator and head of Leukemia Unit at Humanitas Cancer
Center in Milan, Italy. “Results from the COMMANDS study underscore
the clinical value of Reblozyl as an initial treatment for anemia
in patients with low- to intermediate-risk MDS, and this approval
represents a significant milestone towards improving treatment
practice and offering better outcomes for patients.”
*Centralized Marketing Authorization does not include approval
in Great Britain (England, Scotland and Wales).
About COMMANDS
COMMANDS (NCT03682536) is a Phase 3, open-label, randomized
study evaluating the efficacy and safety of Reblozyl versus epoetin
alfa for the treatment of anemia due to very low-, low- or
intermediate-risk (IPSS-R) myelodysplastic syndromes (MDS) in
patients who are red blood cell (RBC) transfusion dependent and
were erythropoiesis stimulating agent (ESA)-naïve.
The primary endpoint evaluated in this study is RBC transfusion
independence (RBC-TI) for 12 weeks with a mean hemoglobin (Hb)
increase ≥1.5 g/dL. Key secondary endpoints include erythroid
response (HI-E) of at least 8 weeks during weeks 1-24 of the study,
RBC-TI ≥12 weeks and RBC-TI for 24 weeks. Eligible patients were
≥18 years old with lower-risk MDS who require transfusions.
Patients were randomized 1:1 to receive subcutaneous Reblozyl
(starting dose 1.0 mg/kg, titration up to 1.75 mg/kg) once every 3
weeks or epoetin alfa (starting dose 450 IU/kg, titration up to
1050 IU/kg) weekly for ≥24 weeks.
At the time of the primary analysis (March 31, 2023), 363
patients were randomized 1:1 to Reblozyl and epoetin alfa. Results
from the primary analysis of the intent to treat (ITT) population
showed:
- 60.4% (n=110) of patients receiving Reblozyl vs. 34.8% (n=63)
of patients receiving epoetin alfa achieved the primary endpoint of
RBC-TI of at least 12 weeks with concurrent mean Hb increase of at
least 1.5 g/dL within the first 24 weeks (p<0.0001).
- HI-E increase of at least 8 weeks was achieved by 74.2% (n=135)
of Reblozyl patients vs. 53% (n=96) of epoetin alfa patients
(p<0.0001).
- RBC-TI of at least 12 weeks was achieved by 68.1% (n=124) of
Reblozyl patients vs. 48.6% (n=88) of epoetin alfa patients
(p<0.0001).
- Duration of response was 128.1 weeks (108.3-NE) for Reblozyl in
patients who achieved TI for at least 12 weeks (achieved weeks
1-24) compared to 89.7 weeks (55.9-157.3) for epoetin alfa (Hazard
Ratio [HR]: 0.534; 95% Confidence Interval [CI]: 0.330-0.864,
p=0.0096).
Safety results were consistent with previous MDS studies, and
progression to acute myeloid leukemia and total deaths were similar
between both arms of the study. The most common treatment-emergent
adverse events in at least 10% of patients were diarrhea, fatigue,
COVID-19, hypertension, dyspnea, nausea, peripheral edema,
asthenia, dizziness, anemia, back pain and headache. Rates of
reported fatigue and asthenia were shown to decrease over time.
About MDS
Myelodysplastic syndromes (MDS) are a group of closely related
blood cancers characterized by ineffective production of healthy
red blood cells (RBC), white blood cells and platelets, which can
lead to anemia and frequent or severe infections. People with MDS
who develop anemia often require blood transfusions to increase the
number of healthy RBCs in circulation. Frequent transfusions are
associated with an increased risk of iron overload, transfusion
reactions and infections. Patients who become RBC
transfusion-dependent have a significantly shorter overall survival
than those who are not dependent on transfusions, partially due to
iron overload or to more severe bone marrow disease than in
non-transfusion dependent patients.
About Reblozyl®
(luspatercept)
REBLOZYL, a first-in-class therapeutic option, promotes
expansion and maturation of late-stage red blood cells in animal
models. Reblozyl is being developed and commercialized through a
global collaboration and North American co-promotion with Merck
following Merck’s acquisition of Acceleron Pharma, Inc. in November
2021.
E.U. Indications:
REBLOZYL is indicated in the E.U. for the treatment of:
- adult patients with transfusion-dependent anaemia due to very
low, low and intermediate-risk myelodysplastic syndromes
(MDS).
- adult patients with anaemia associated with
transfusion-dependent and non-transfusion-dependent
beta-thalassaemia.
A European Summary of Product Characteristics for REBLOZYL is
available from the European Medicines Agency website at
www.ema.europa.eu.
U.S. Indications:
REBLOZYL is indicated in the U.S. for the treatment of:
- anemia in adult patients with beta thalassemia who require
regular red blood cell (RBC) transfusions.
- anemia without previous erythropoiesis stimulating agent use
(ESA-naïve) in adult patients with very low- to intermediate-risk
myelodysplastic syndromes (MDS) who may require regular red blood
cell (RBC) transfusions.
- anemia failing an erythropoiesis stimulating agent and
requiring 2 or more red blood cell (RBC) units over 8 weeks in
adult patients with very low- to intermediate-risk myelodysplastic
syndrome with ring sideroblasts (MDS-RS) or with
myelodysplastic/myeloproliferative neoplasm with ring sideroblasts
and thrombocytosis (MDS/MPN-RS-T).
REBLOZYL is not indicated for use as a substitute for RBC
transfusions in patients who require immediate correction of
anemia. In the U.S., REBLOZYL is not indicated for use in patients
with non-transfusion-dependent beta thalassemia.
U.S. Important Safety Information:
WARNINGS AND PRECAUTIONS
Thrombosis/Thromboembolism
In adult patients with beta thalassemia, thromboembolic events
(TEE) were reported in 8/223 (3.6%) of 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 11.4% (63/554) of REBLOZYL-treated
patients. Across clinical studies, the incidence of Grade 3 to 4
hypertension ranged from 2% to 9.6%. 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. In
ESA-refractory or -intolerant adult patients with MDS with normal
baseline blood pressure, 26 (30%) patients developed SBP ≥130 mm Hg
and 23 (16%) patients developed DBP ≥80 mm Hg. In ESA-naïve adult
patients with MDS with normal baseline blood pressure, 23 (36%)
patients developed SBP ≥140 mm Hg and 11 (6%) patients developed
DBP ≥80 mm Hg. Monitor blood pressure prior to each administration.
Manage new or exacerbations of preexisting hypertension using
anti-hypertensive agents.
Extramedullary Hematopoietic (EMH) Masses
In adult patients with transfusion-dependent beta thalassemia,
EMH masses were observed in 3.2% of REBLOZYL-treated patients, with
spinal cord compression symptoms due to EMH masses occurring in
1.9% of patients (BELIEVE and REBLOZYL long-term follow-up
study).
In a study of adult patients with non-transfusion-dependent beta
thalassemia, a higher incidence of EMH masses was observed in 6.3%
of REBLOZYL-treated patients vs. 2% of placebo-treated patients in
the double-blind phase of the study, with spinal cord compression
due to EMH masses occurring in 1 patient with a prior history of
EMH. REBLOZYL is not indicated for use in patients with
non-transfusion-dependent beta thalassemia.
Possible risk factors for the development of EMH masses in
patients with beta thalassemia include history of EMH masses,
splenectomy, splenomegaly, hepatomegaly, or low baseline hemoglobin
(<8.5 g/dL). Signs and symptoms may vary depending on the
anatomical location. Monitor patients with beta thalassemia at
initiation and during treatment for symptoms and signs or
complications resulting from the EMH masses and treat according to
clinical guidelines. Discontinue treatment with REBLOZYL in case of
serious complications due to EMH masses. Avoid use of REBLOZYL in
patients requiring treatment to control the growth of EMH
masses.
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 final dose.
ADVERSE REACTIONS
Beta-Thalassemia
Serious adverse reactions occurred in 3.6% of patients on
REBLOZYL. 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%).
ESA-naïve adult patients with Myelodysplastic
Syndromes
Grade ≥3 (≥2%) adverse reactions included hypertension and
dyspnea.
The most common (≥10%) all-grade adverse reactions included
diarrhea, fatigue, hypertension, peripheral edema, nausea, and
dyspnea.
ESA-refractory or -intolerant adult patients with
Myelodysplastic Syndromes
Grade ≥3 (≥2%) adverse reactions included fatigue, hypertension,
syncope and musculoskeletal pain. A fatal adverse reaction occurred
in 5 (2.1%) patients.
The most common (≥10%) adverse reactions included fatigue,
musculoskeletal pain, dizziness, diarrhea, nausea, hypersensitivity
reactions, hypertension, headache, upper respiratory tract
infection, bronchitis, and urinary tract infection.
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.
DRUG ABUSE POTENTIAL
Abuse: Abuse of REBLOZYL may be seen in athletes for the effects
on erythropoiesis. Misuse of drugs that increase erythropoiesis,
such as REBLOZYL, by healthy persons may lead to polycythemia,
which may be associated with life-threatening cardiovascular
complications.
Please see accompanying U.S. Full Prescribing Information for
REBLOZYL.
Bristol Myers Squibb: Creating a Better
Future for People with Cancer
Bristol Myers Squibb is inspired by a single vision —
transforming patients’ lives through science. The goal of the
company’s cancer research is to deliver medicines that offer each
patient a better, healthier life and to make cure a possibility.
Building on a legacy across a broad range of cancers that have
changed survival expectations for many, Bristol Myers Squibb
researchers are exploring new frontiers in personalized medicine
and, through innovative digital platforms, are turning data into
insights that sharpen their focus. Deep understanding of causal
human biology, cutting-edge capabilities and differentiated
research platforms uniquely position the company to approach cancer
from every angle.
Cancer can have a relentless grasp on many parts of a patient’s
life, and Bristol Myers Squibb is committed to taking actions to
address all aspects of care, from diagnosis to survivorship. As a
leader in cancer care, Bristol Myers Squibb is working to empower
all people with cancer to have a better future.
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
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Forward-Looking Statement of Bristol
Myers Squibb
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 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 the outcome of pricing and reimbursement negotiations in
individual countries in Europe may delay or limit the commercial
potential of Reblozyl® (luspatercept) for the indication
described in this release, that any marketing approvals, if
granted, may have significant limitations on their use, that
continued approval of such product candidate for such indication
described in this release may be contingent upon verification and
description of clinical benefit in confirmatory trials, and whether
such product candidate for such indication described in this
release will be commercially successful. No Forward-looking
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Forward-looking statements in this press release should be
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the year ended December 31, 2023, as updated by our subsequent
Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and
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a result of new information, future events, changed circumstances
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