Reblozyl is the first and only therapy to
demonstrate superiority compared to an erythropoiesis stimulating
agent (ESA) in MDS-related anemia based on interim results from
pivotal Phase 3 COMMANDS trial, expanding approved population to
ESA-naïve patients, regardless of ring sideroblast status
In head-to-head study, results showed
Reblozyl nearly doubled the percent of patients achieving primary
endpoint of concurrent transfusion independence and hemoglobin (Hb)
increase vs. epoetin alfa, with a well-established safety
profile
Bristol Myers Squibb (NYSE: BMY) today announced that the U.S.
Food and Drug Administration (FDA) has approved Reblozyl®
(luspatercept-aamt) for the treatment of 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. This
expanded indication to the first-line setting is based on interim
results from the pivotal Phase 3 COMMANDS trial, in which Reblozyl
demonstrated superior efficacy of concurrent RBC transfusion
independence (RBC-TI) and hemoglobin (Hb) increase compared to
epoetin alfa, an ESA, regardless of ring sideroblast status. These
results underscore Reblozyl’s ability to address chronic anemia
earlier in the treatment journey in a broader range of
patients.
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“For patients with lower-risk MDS, current standard therapies,
including ESAs, have provided limited benefit in controlling anemia
with only 1 in 3 patients responding for a duration of 6-18
months,” said Guillermo Garcia-Manero, M.D., lead investigator and
Chief of the Section of Myelodysplastic Syndromes at The University
of Texas MD Anderson Cancer Center. “Results from the COMMANDS
study showed nearly twice as many patients treated with Reblozyl
achieved transfusion independence of at least 12 weeks and
concurrent hemoglobin increase compared to epoetin alfa. Today’s
approval represents an important advancement for patients with
lower-risk MDS.”
In the Phase 3 COMMANDS trial, results showed 58.5% (n=86) of
patients treated with Reblozyl vs. 31.2% (n=48) of patients treated
with epoetin alfa achieved the primary endpoint of RBC-TI of at
least 12 weeks with a mean Hb increase of at least 1.5 g/dL within
the first 24 weeks (p<0.0001). The most common (>10%) adverse
reactions were diarrhea, fatigue, hypertension, peripheral edema,
nausea, and dyspnea.
“Today's expanded approval of Reblozyl marks an important
milestone in our commitment to MDS patients with anemia by
providing a durable and more effective treatment option, with more
convenient and less frequent administration,” said Wendy
Short-Bartie, senior vice president and general manager, U.S.
Hematology and Cell Therapy, Bristol Myers Squibb. “We remain
dedicated to addressing hard-to-treat diseases with significant
burden to patients and look forward to bringing this important
option earlier in the treatment process.”
“The majority of patients with MDS experience chronic anemia and
require RBC transfusions,” said Tracey Iraca, executive director,
MDS Foundation. “The approval of Reblozyl in the first-line
treatment of anemia for patients with lower-risk MDS represents a
crucial step in making transfusion independence possible for more
patients.”
Results from the COMMANDS study were featured in June as part of
the press program at the American Society of Clinical Oncology
(ASCO) Annual Meeting and plenary session at the European
Hematology Association (EHA) Congress, with simultaneous
publication in The Lancet. Reblozyl is being developed and
commercialized through a global collaboration with Merck as of
November 2021.
COMMANDS Study Results
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 syndrome (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. The majority of study
participants (>90%) were outside of the United States and a
non-U.S.-licensed epoetin alfa product was used in the control arm
for such patients.
At the time of the planned interim analysis (October 31, 2022),
147 evaluable patients received Reblozyl and 154 evaluable patients
received epoetin alfa, with median treatment durations of 41.6 and
27 weeks, respectively. Results published in The Lancet showed:
- 58.5% (n=86) of patients receiving Reblozyl vs. 31.2% (n=48) 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 74.1% (n=109)
of Reblozyl patients vs. 51.3% (n=79) of epoetin alfa patients
(p<0.0001).
- Within the first 24 weeks of treatment, RBC-TI of at least 24
weeks was achieved by 47.6% (n=70) of Reblozyl patients vs. 29.2%
(n=45) of epoetin alfa patients (p=0.0012).
- RBC-TI of at least 12 weeks was achieved by 66.7% (n=98) of
Reblozyl patients vs. 46.1% (n=71) of epoetin alfa patients
(p=0.0003).
Patients treated with Reblozyl demonstrated durable responses
with nearly 2.5 years of median RBC-TI ≥12 weeks (126.6 weeks, week
1 to end of treatment). The most common (>10%) adverse reactions
were diarrhea, fatigue, hypertension, peripheral edema, nausea, and
dyspnea.
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-aamt) Reblozyl, a first-in-class
therapeutic option, promotes late-stage red blood cell maturation
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. As part of the collaboration, Merck receives
milestone and royalty payments. With this approval, 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, and
- 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 people’s 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 scientific expertise,
cutting-edge capabilities and discovery platforms enable the
company to look at 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. Because 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,
whether Reblozyl® (luspatercept-aamt) for the additional
indication described in this release will be commercially
successful, any marketing approvals, if granted, may have
significant limitations on their use, and that continued approval
of such product candidate for such additional indication described
in this release may be contingent upon verification and description
of clinical benefit in confirmatory trials. 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,
2022, 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
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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.
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