The supplemental Biologics License
Application for Abecma in this indication remains under review with
the FDA; Abecma has been approved in Japan and Switzerland and
received a positive CHMP Opinion by the European Medicines Agency
based on KarMMa-3
Bristol Myers Squibb (NYSE: BMY) and 2seventy bio, Inc. (Nasdaq:
TSVT) today announced that the U.S. Food and Drug Administration
(FDA) Oncologic Drugs Advisory Committee (ODAC) voted positively
(8-3) that Abecma (idecabtagene vicleucel) demonstrated a favorable
benefit/risk profile for patients with triple-class exposed
relapsed or refractory multiple myeloma based on results from the
pivotal Phase 3 KarMMa-3 study, including the key secondary
endpoint of overall survival. The recommendation from the ODAC will
be considered by the FDA during its ongoing review of the
supplemental Biologics License Application (sBLA) for Abecma for
this patient population. The FDA has not yet assigned a new target
action date for review of the sBLA.
“We are extremely pleased with the positive outcome of the ODAC
meeting, which recognizes the favorable benefit/risk profile of
Abecma, and based on results from the KarMMa-3 study, we are
confident in the significant clinical benefit that Abecma delivers
for patients with triple-class exposed relapsed or refractory
multiple myeloma, an incurable disease with no clear effective
standard of care in earlier lines of therapy,” said Anne Kerber,
senior vice president, head of Late Clinical Development,
Hematology, Oncology and Cell Therapy, Bristol Myers Squibb. “We
look forward to working with the FDA as it completes review of our
sBLA in order to bring this potentially transformative therapy to
more patients in need.”
“The favorable and supportive outcome of the ODAC meeting brings
us another step closer to expanding the benefits of Abecma to
myeloma patients earlier in their treatment course,” said Anna
Truppel-Hartmann, senior vice president, Clinical Research and
Development, 2seventy bio. “We believe in the strength of the
KarMMa-3 data and remain committed to increasing treatment options
and improving outcomes for patients living with multiple
myeloma.”
The positive vote from the ODAC followed discussion of the
interim overall survival data from the KarMMa-3 study which was
presented at the 2023 American Society of Hematology (ASH) Annual
Meeting and Exposition in December 2023.
“With patients becoming triple-class exposed earlier in the
multiple myeloma treatment paradigm, it is critical that new
treatment options with the potential to improve long-term outcomes
are available as early as possible,” said Sagar Lonial, MD, FACP,
professor and chair, Department of Hematology & Medical
Oncology, Emory University School of Medicine, chief medical
officer, Winship Cancer Institute of Emory University. “We are
thankful that today’s ODAC vote recognizes this unmet need and
helps to advance ide-cel, a novel treatment option with
demonstrated clinically meaningful benefit, for patients with
triple-class exposed relapsed or refractory multiple myeloma.”
Abecma was recently approved in Japan and Switzerland for
patients with relapsed and/or refractory multiple myeloma who have
received at least two prior therapies, including an
immunomodulatory agent, a proteasome inhibitor, and an anti-CD38
antibody based on the KarMMa-3 study, making it the first CAR T
cell therapy to receive regulatory approval for use in earlier
lines of therapy for patients with relapsed or refractory multiple
myeloma. Abecma also received a positive opinion from the Committee
for Medicinal Products for Human Use (CHMP) of the European
Medicines Agency (EMA) for the extension of indication to include
the treatment of patients with triple-class exposed relapsed and
refractory multiple myeloma after at least two prior therapies,
including an immunomodulatory agent, a proteasome inhibitor and an
anti-CD38 antibody and have demonstrated disease progression on the
last therapy.
About Abecma
Abecma is a CAR T cell therapy that recognizes and binds to the
B-cell maturation antigen (BCMA) on the surface of multiple myeloma
cells leading to CAR T cell proliferation, cytokine secretion, and
subsequent cytolytic killing of BCMA-expressing cells. Abecma is
the first-in-class BCMA-directed CAR T cell immunotherapy approved
by the U.S. FDA for the treatment of adult patients with relapsed
or refractory multiple myeloma after four or more prior lines of
therapy, including an immunomodulatory agent, a proteasome
inhibitor, and an anti-CD38 monoclonal antibody. Please see the
Important Safety Information section below, including Boxed
WARNINGS for Abecma regarding CRS, neurologic toxicities,
Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome
and Prolonged Cytopenia. Abecma is being jointly developed and
commercialized in the U.S. as part of a Co-Development,
Co-Promotion, and Profit Share Agreement between Bristol Myers
Squibb and 2seventy bio.
Abecma is also approved in the European Union, Switzerland,
Japan, the United Kingdom and Israel for adult patients with
triple-class exposed relapsed or refractory multiple myeloma after
three to four or more prior lines of therapy. Bristol Myers Squibb
assumes sole responsibility for Abecma drug product manufacturing
and commercialization outside of the U.S.
The companies’ broad clinical development program for Abecma
includes ongoing and planned clinical studies (KarMMa-2, KarMMa-9)
for patients with multiple myeloma. For more information visit
clinicaltrials.gov.
U.S. Important Safety
Information
BOXED WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC
TOXICITIES, HLH/MAS, AND PROLONGED CYTOPENIA
- Cytokine Release Syndrome (CRS), including fatal or
life-threatening reactions, occurred in patients following
treatment with ABECMA. Do not administer ABECMA to patients with
active infection or inflammatory disorders. Treat severe or
life-threatening CRS with tocilizumab or tocilizumab and
corticosteroids.
- Neurologic Toxicities, which may be severe or life-threatening,
occurred following treatment with ABECMA, including concurrently
with CRS, after CRS resolution, or in the absence of CRS. Monitor
for neurologic events after treatment with ABECMA. Provide
supportive care and/or corticosteroids as needed.
- Hemophagocytic Lymphohistiocytosis/Macrophage Activation
Syndrome (HLH/MAS) including fatal and life-threatening reactions,
occurred in patients following treatment with ABECMA. HLH/MAS can
occur with CRS or neurologic toxicities.
- Prolonged Cytopenia with bleeding and infection, including
fatal outcomes following stem cell transplantation for
hematopoietic recovery, occurred following treatment with
ABECMA.
- ABECMA is available only through a restricted program under a
Risk Evaluation and Mitigation Strategy (REMS) called the ABECMA
REMS.
WARNINGS AND PRECAUTIONS:
Cytokine Release Syndrome (CRS): CRS, including fatal or
life-threatening reactions, occurred following treatment with
ABECMA in 85% (108/127) of patients. Grade 3 or higher CRS occurred
in 9% (12/127) of patients, with Grade 5 CRS reported in one (0.8%)
patient. The median time to onset of CRS, any grade, was 1 day
(range: 1 - 23 days) and the median duration of CRS was 7 days
(range: 1 - 63 days). The most common manifestations included
pyrexia, hypotension, tachycardia, chills, hypoxia, fatigue, and
headache. Grade 3 or higher events that may be associated with CRS
include hypotension, hypoxia, hyperbilirubinemia,
hypofibrinogenemia, acute respiratory distress syndrome (ARDS),
atrial fibrillation, hepatocellular injury, metabolic acidosis,
pulmonary edema, multiple organ dysfunction syndrome, and
HLH/MAS.
Identify CRS based on clinical presentation. Evaluate for and
treat other causes of fever, hypoxia, and hypotension. CRS has been
reported to be associated with findings of HLH/MAS, and the
physiology of the syndromes may overlap. In patients with
progressive symptoms of CRS or refractory CRS despite treatment,
evaluate for evidence of HLH/MAS.
Fifty four percent (68/127) of patients received tocilizumab
(single dose: 35%; more than 1 dose: 18%). Overall, 15% (19/127) of
patients received at least 1 dose of corticosteroids for treatment
of CRS. All patients that received corticosteroids for CRS received
tocilizumab. Ensure that a minimum of 2 doses of tocilizumab are
available prior to infusion of ABECMA.
Monitor patients at least daily for 7 days following ABECMA
infusion at the REMS-certified healthcare facility for signs or
symptoms of CRS and monitor patients for signs or symptoms of CRS
for at least 4 weeks after ABECMA infusion. At the first sign of
CRS, institute treatment with supportive care, tocilizumab and/or
corticosteroids as indicated.
Counsel patients to seek immediate medical attention should
signs or symptoms of CRS occur at any time.
Neurologic Toxicities: Neurologic toxicities, which may
be severe or life-threatening, occurred following treatment with
ABECMA in 28% (36/127) of patients receiving ABECMA, including
Grade 3 in 4% (5/127) of patients. One patient had ongoing Grade 2
neurotoxicity at the time of death. Two patients had ongoing Grade
1 tremor at the time of data cutoff. The median time to onset of
neurotoxicity was 2 days (range: 1 - 42 days). CAR T
cell-associated neurotoxicity resolved in 92% (33/36) of patients
with a median time to resolution of 5 days (range: 1 - 61 days).
The median duration of neurotoxicity was 6 days (range: 1 - 578) in
all patients including 3 patients with ongoing neurotoxicity.
Thirty-four patients with neurotoxicity had CRS with onset in 3
patients before, 29 patients during, and 2 patients after CRS. The
most frequently reported manifestations of CAR T cell-associated
neurotoxicity include encephalopathy, tremor, aphasia, and
delirium. Grade 4 neurotoxicity and cerebral edema in 1 patient,
Grade 3 myelitis, and Grade 3 parkinsonism have been reported with
ABECMA in another study in multiple myeloma.
Monitor patients at least daily for 7 days following ABECMA
infusion at the REMS-certified healthcare facility for signs or
symptoms of neurologic toxicities and monitor patients for signs or
symptoms of neurologic toxicities for at least 4 weeks after ABECMA
infusion and treat promptly. Rule out other causes of neurologic
symptoms. Neurologic toxicity should be managed with supportive
care and/or corticosteroids as needed.
Counsel patients to seek immediate medical attention should
signs or symptoms occur at any time.
Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage
Activation Syndrome (MAS): HLH/MAS occurred in 4% (5/127) of
patients receiving ABECMA. One patient developed fatal multi-organ
HLH/MAS with CRS and another patient developed fatal
bronchopulmonary aspergillosis with contributory HLH/MAS. Three
cases of Grade 2 HLH/MAS resolved. All events of HLH/MAS had onset
within 10 days of receiving ABECMA with a median onset of 7 days
(range: 4 - 9 days) and occurred in the setting of ongoing or
worsening CRS. Two patients with HLH/MAS had overlapping
neurotoxicity. The manifestations of HLH/MAS include hypotension,
hypoxia, multiple organ dysfunction, renal dysfunction, and
cytopenia. HLH/MAS is a potentially life-threatening condition with
a high mortality rate if not recognized early and treated.
Treatment of HLH/MAS should be administered per institutional
guidelines.
ABECMA REMS: Due to the risk of CRS and neurologic
toxicities, ABECMA is available only through a restricted program
under a Risk Evaluation and Mitigation Strategy (REMS) called the
ABECMA REMS. Further information is available at www.AbecmaREMS.com
or 1-888-423-5436.
Hypersensitivity Reactions: Allergic reactions may occur
with the infusion of ABECMA. Serious hypersensitivity reactions,
including anaphylaxis, may be due to dimethyl sulfoxide (DMSO) in
ABECMA.
Infections: ABECMA should not be administered to patients
with active infections or inflammatory disorders. Severe,
life-threatening, or fatal infections occurred in patients after
ABECMA infusion. Infections (all grades) occurred in 70% of
patients. Grade 3 or 4 infections occurred in 23% of patients.
Overall, 4 patients had Grade 5 infections (3%); 2 patients (1.6%)
had Grade 5 events of pneumonia, 1 patient (0.8%) had Grade 5
bronchopulmonary aspergillosis, and 1 patient (0.8%) had
cytomegalovirus (CMV) pneumonia associated with Pneumocystis
jirovecii. Monitor patients for signs and symptoms of infection
before and after ABECMA infusion and treat appropriately.
Administer prophylactic, pre-emptive, and/or therapeutic
antimicrobials according to standard institutional guidelines.
Febrile neutropenia was observed in 16% (20/127) of patients
after ABECMA infusion and may be concurrent with CRS. In the event
of febrile neutropenia, evaluate for infection and manage with
broad-spectrum antibiotics, fluids, and other supportive care.
Viral Reactivation: CMV infection resulting in pneumonia and
death has occurred following ABECMA administration. Monitor and
treat for CMV reactivation in accordance with clinical guidelines.
Hepatitis B virus (HBV) reactivation, in some cases resulting in
fulminant hepatitis, hepatic failure, and death, can occur in
patients treated with drugs directed against plasma cells. Perform
screening for CMV, HBV, hepatitis C virus (HCV), and human
immunodeficiency virus (HIV) in accordance with clinical guidelines
before collection of cells for manufacturing.
Prolonged Cytopenias: In the clinical study, 41% of
patients (52/127) experienced prolonged Grade 3 or 4 neutropenia
and 49% (62/127) experienced prolonged Grade 3 or 4
thrombocytopenia that had not resolved by Month 1 following ABECMA
infusion. In 83% (43/52) of patients who recovered from Grade 3 or
4 neutropenia after Month 1, the median time to recovery from
ABECMA infusion was 1.9 months. In 65% (40/62) of patients who
recovered from Grade 3 or 4 thrombocytopenia, the median time to
recovery was 2.1 months.
Three patients underwent stem cell therapy for hematopoietic
reconstitution due to prolonged cytopenia. Two of the three
patients died from complications of prolonged cytopenia. Monitor
blood counts prior to and after ABECMA infusion. Manage cytopenia
with myeloid growth factor and blood product transfusion
support.
Hypogammaglobulinemia: Hypogammaglobulinemia was reported
as an adverse event in 21% (27/127) of patients; laboratory IgG
levels fell below 500 mg/dl after infusion in 25% (32/127) of
patients treated with ABECMA.
Monitor immunoglobulin levels after treatment with ABECMA and
administer IVIG for IgG <400 mg/dl. Manage appropriately per
local institutional guidelines, including infection precautions and
antibiotic or antiviral prophylaxis.
The safety of immunization with live viral vaccines during or
after ABECMA treatment has not been studied. Vaccination with live
virus vaccines is not recommended for at least 6 weeks prior to the
start of lymphodepleting chemotherapy, during ABECMA treatment, and
until immune recovery following treatment with ABECMA.
Secondary Malignancies: Patients treated with ABECMA may
develop secondary malignancies. Monitor life-long for secondary
malignancies. If a secondary malignancy occurs, contact
Bristol-Myers Squibb at 1-888-805-4555 to obtain instructions on
patient samples to collect for testing of secondary malignancy of T
cell origin.
Effects on Ability to Drive and Operate Machinery: Due to
the potential for neurologic events, patients receiving ABECMA are
at risk for altered or decreased consciousness or coordination in
the 8 weeks following ABECMA infusion. Advise patients to refrain
from driving and engaging in hazardous occupations or activities,
such as operating heavy or potentially dangerous machinery, during
this initial period.
Adverse Reactions: The most common nonlaboratory adverse
reactions include CRS, infections – pathogen unspecified, fatigue,
musculoskeletal pain, hypogammaglobulinemia, diarrhea, upper
respiratory tract infection, nausea, viral infections,
encephalopathy, edema, pyrexia, cough, headache, and decreased
appetite.
Please see full Prescribing Information, including Boxed
WARNINGS and Medication Guide.
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.
Learn more about the science behind cell therapy and ongoing
research at Bristol Myers Squibb here.
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 2seventy bio
Our name, 2seventy bio, reflects why we do what we do - TIME.
Cancer rips time away, and our goal is to work at the maximum speed
of translating human thought into action – 270 miles per hour – to
give the people we serve more time. With a deep understanding of
the human body’s immune response to tumor cells and how to
translate cell therapies into practice, we’re applying this
knowledge to deliver the first FDA-approved CAR T cell therapy for
multiple myeloma. We are focused on delivering therapies that are
designed with the goal to “think” smarter and faster than the
disease. Importantly, we remain focused on accomplishing these
goals by staying genuine and authentic to our “why” and keeping our
people and culture top of mind every day.
For more information, visit www.2seventybio.com.
Follow 2seventy bio on social media: Twitter and LinkedIn.
2seventy bio is a trademark of 2seventy bio, Inc.
Bristol Myers Squibb 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 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 may not be consistent with the results to
date, that Abecma® (idecabtagene vicleucel) may not receive
regulatory approval for the additional indication described in this
release in the currently anticipated timeline or at all, that any
marketing approvals, if granted, may have significant limitations
on their use, and, if approved, whether such product candidate for
such additional indication described in this release will be
commercially successful. No forward-looking statement can be
guaranteed. It should also be noted that acceptance of the sBLA
does not change the standards for FDA approval, that validation by
the EMA of the application does not change the standards for EMA
approval, and that acceptance of the sNDA does not change the
standards for Japan’s Ministry of Health, Labour and Welfare
approval. 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, 2023, 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.
2seventy bio Cautionary Note 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 Abecma® (idecabtagene vicleucel). 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, the possibility that Abecma
may not receive FDA approval for the indication described in this
release in the currently anticipated timeline or at all, that any
marketing approvals, if granted, may have significant limitations
on their use, that future study results may not be consistent with
the results to date, that Abecma may not be commercially successful
and that collaboration with Bristol Myers Squibb may not continue
or be 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 2seventy bio’s business, particularly those identified in
the risk factors discussion in 2seventy bio’s Annual Report on Form
10-K, 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, 2seventy bio
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.
Hyperlinks are provided as a convenience and for informational
purposes only. Neither Bristol Myers Squibb nor 2seventy bio bears
responsibility for the security or content of external websites or
websites outside of their respective control.
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2seventy bio
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jenn.snyder@2seventybio.com
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