Median progression-free survival and overall
response rate doubled among patients receiving EPd compared to
pomalidomide and low-dose dexamethasone alone
Second Empliciti-based combination approved
in Europe for patients with relapsed and refractory multiple
myeloma
Bristol-Myers Squibb Company (NYSE:
BMY) today announced that the European Commission (EC) has approved
Empliciti (elotuzumab) plus pomalidomide and low-dose dexamethasone
(EPd) for the treatment of adult patients with relapsed and
refractory multiple myeloma who have received at least two prior
therapies, including lenalidomide and a proteasome inhibitor (PI),
and have demonstrated disease progression on the last therapy. This
approval is based on data from the ELOQUENT-3 trial in which EPd
doubled both median progression-free survival (PFS) and overall
response rate (ORR) among patients with relapsed and refractory
multiple myeloma versus pomalidomide and low-dose dexamethasone
(Pd) alone.
“Multiple myeloma is a frequently recurring disease and the
chance it will return after initial treatment is a heavy burden for
patients to carry,” said Fouad Namouni, M.D., head, Oncology
Development, Bristol-Myers Squibb. “We are proud that the European
Commission has again recognized the role of Empliciti in helping
European patients with multiple myeloma by approving a second
Empliciti-based regimen in the relapsed and refractory
setting.”
EPd is the first triplet combination approved in Europe based on
a randomized clinical trial using the standard of care, Pd, as a
comparator. Results from ELOQUENT-3 demonstrated that the addition
of Empliciti to Pd can significantly prolong survival without
disease progression among heavily pretreated patients with multiple
myeloma regardless of the number of prior therapies received.
Investigator-assessed PFS, the study’s primary endpoint, was 10.25
months (95% CI: 5.59 to not estimable) among patients randomized to
EPd compared with 4.67 months (95% CI: 2.83 to 7.16) among patients
treated with Pd alone, indicating a 46% reduction in risk of
disease progression (HR 0.54; 95% CI: 0.34 to 0.86; p=0.0078)
between EPd and Pd arms after a minimum follow-up of 9.1 months. A
secondary endpoint of the study, ORR, was 53.3% (95% CI: 40.0 to
66.3) compared with 26.3% (95% CI: 15.5 to 39.7; p=0.0029) among
patients receiving EPd or Pd, respectively.
“The approval of this elotuzumab-based triplet combination in
the relapsed and refractory setting gives patients, and their
doctors, a treatment alternative shown to have the potential to
offer patients more time living without disease progression,
coupled with a tolerable safety profile,” said Meletios A.
Dimopoulos, M.D., professor and chairman of the Department of
Clinical Therapeutics at National and Kapodistrian University of
Athens.
Data from the ELOQUENT-3 trial were first presented at the 23rd
Congress of the European Hematology Association (EHA) in 2018.
Updated efficacy results with a minimum follow-up of 18.3 months
were presented at the 24th Congress of the EHA this year. In this
exploratory analysis, a total of 40 (67%) patients were alive in
the EPd arm and 29 (51%) patients were alive in the Pd arm (HR
0.54; 95% CI: 0.30 to 0.96). Median OS was not reached for the EPd
treatment arm.
Treatment-related Grade 3-4 adverse events (AEs) were comparable
between EPd and Pd groups. Any-grade infections occurred in 65% of
patients in both arms. Rates of the most commonly occurring Grade
3-4 hematologic AEs, neutropenia and anemia, were 13% and 10%,
respectively, for patients receiving EPd and 27% and 20%,
respectively, for patients receiving Pd, despite longer exposure
within the EPd arm and similar dose intensity of pomalidomide
between arms. AEs led to discontinuation in 18% of patients in the
EPd arm, compared with 24% of patients in the Pd arm.
The U.S. Food and Drug Administration (FDA) approved EPd for the
treatment of adult patients with multiple myeloma who have received
at least two prior therapies, including lenalidomide and a PI, in
November 2018.
Bristol-Myers Squibb and AbbVie are co-developing Empliciti,
with Bristol-Myers Squibb solely responsible for commercial
activities.
About ELOQUENT-3
The Phase 2 ELOQUENT-3 trial randomized 117 patients with
relapsed and refractory multiple myeloma to treatment with EPd
(n=60) or Pd (n=57) in 28-day cycles until disease progression or
unacceptable toxicity. In the EPd arm, Empliciti was administered
intravenously at the dose of 10 mg/kg each week for the first 2
cycles and 20 mg/kg every four week thereafter. The median number
of treatment cycles was nine for the EPd arm and five for the Pd
arm.
Bristol-Myers Squibb: Advancing
Oncology Research
At Bristol-Myers Squibb, patients are at the center of
everything we do. The focus of our research is to increase quality,
long-term survival for patients and make cure a possibility.
Through a unique multidisciplinary approach powered by
translational science, we harness our deep scientific experience in
oncology and Immuno-Oncology (I-O) research to identify novel
treatments tailored to individual patient needs. Our researchers
are developing a diverse, purposefully built pipeline designed to
target different immune system pathways and address the complex and
specific interactions between the tumor, its microenvironment and
the immune system. We source innovation internally, and in
collaboration with academia, government, advocacy groups and
biotechnology companies, to help make the promise of
transformational medicines, like I-O, a reality for patients.
About Empliciti
Empliciti is an immunostimulatory antibody that specifically
targets Signaling Lymphocyte Activation Molecule Family member 7
(SLAMF7), a cell-surface glycoprotein. SLAMF7 is expressed on
myeloma cells independent of cytogenetic abnormalities. SLAMF7 also
is expressed on Natural Killer cells, plasma cells and at lower
levels on specific immune cell subsets of differentiated cells
within the hematopoietic lineage.
Empliciti has a dual mechanism of action. It directly activates
the immune system through Natural Killer cells via the SLAMF7
pathway. Empliciti also targets SLAMF7 on myeloma cells, tagging
these malignant cells for Natural Killer cell-mediated destruction
via antibody-dependent cellular toxicity.
Empliciti was initially approved by the FDA in 2015 in
combination with lenalidomide and dexamethasone (ELd) for the
treatment of patients with multiple myeloma who have received one
to three prior therapies. In 2018, Empliciti was approved by the
FDA in a new combination, with pomalidomide and dexamethasone, for
the treatment of patients with multiple myeloma who have received
at least two prior therapies, including lenalidomide and a PI. The
ELd and EPd indications were subsequently approved by the EC in
2016 and 2019, respectively.
U.S. FDA-APPROVED INDICATIONS FOR
EMPLICITI®
EMPLICITI® (elotuzumab) is indicated in combination with
lenalidomide and dexamethasone for the treatment of adult patients
with multiple myeloma who have received one to three prior
therapies.
EMPLICITI® (elotuzumab) is indicated in combination with
pomalidomide and dexamethasone for the treatment of adult patients
with multiple myeloma who have received at least two prior
therapies including lenalidomide and a proteasome inhibitor.
IMPORTANT SAFETY INFORMATION
Infusion Reactions
Infusion reactions were reported in 10% of patients treated with
EMPLICITI in the ELOQUENT-2 trial [EMPLICITI + lenalidomide +
dexamethasone (ERd) vs lenalidomide + dexamethasone (Rd)] and 3.3%
in the ELOQUENT-3 trial [EMPLICITI + pomalidomide + dexamethasone
(EPd) vs pomalidomide + dexamethasone (Pd)].
In the ELOQUENT-2 trial, all infusion reactions were Grade 3 or
lower, with Grade 3 infusion reactions occurring in 1% of patients.
The most common symptoms included fever, chills, and hypertension.
Bradycardia and hypotension also developed during infusions. In the
trial, 5% of patients required interruption of the administration
of EMPLICITI for a median of 25 minutes due to infusion reactions,
and 1% of patients discontinued due to infusion reactions. Of the
patients who experienced an infusion reaction, 70% (23/33) had them
during the first dose.
In the ELOQUENT-3 trial, the only infusion reaction symptom was
chest discomfort (2%), which was Grade 1. All the patients who
experienced an infusion reaction had them during the first
treatment cycle.
If a Grade 2 or higher infusion reaction occurs, interrupt the
EMPLICITI infusion and institute appropriate medical and supportive
measures. If the infusion reaction recurs, stop the EMPLICITI
infusion and do not restart it on that day. Severe infusion
reactions may require permanent discontinuation of EMPLICITI
therapy and emergency treatment.
Premedicate with dexamethasone, H1 blocker, H2 blocker, and
acetaminophen prior to EMPLICITI infusion.
Infections
In the ELOQUENT-2 trial (N=635), infections were reported in 81%
of patients in the ERd arm and 74% in the Rd arm. Grade 3-4
infections were 28% (ERd) and 24% (Rd). Discontinuations due to
infections were 3.5% (ERd) and 4.1% (Rd). Fatal infections were
2.5% (ERd) and 2.2% (Rd). Opportunistic infections were reported in
22% (ERd) and 13% (Rd). Fungal infections were 10% (ERd) and 5%
(Rd). Herpes zoster was 14% (ERd) and 7% (Rd).
In the ELOQUENT-3 trial (N=115), infections were reported in 65%
of patients in both the EPd arm and the Pd arm. Grade 3-4
infections were reported in 13% (EPd) and 22% (Pd).
Discontinuations due to infections were 7% (EPd) and 5% (Pd). Fatal
infections were 5% (EPd) and 3.6% (Pd). Opportunistic infections
were reported in 10% (EPd) and 9% (Pd). Herpes zoster was reported
in 5% (EPd) and 1.8% (Pd).
Monitor patients for development of infections and treat
promptly.
Second Primary Malignancies
In the ELOQUENT-2 trial (N=635), invasive second primary
malignancies (SPM) were 9% (ERd) and 6% (Rd). The rate of
hematologic malignancies was the same between ERd and Rd treatment
arms (1.6%). Solid tumors were reported in 3.5% (ERd) and 2.2%
(Rd). Skin cancer was reported in 4.4% (ERd) and 2.8% (Rd).
In the ELOQUENT-3 trial (N=115), invasive SPMs were 0% (EPd) and
1.8% (Pd).
Monitor patients for the development of SPMs.
Hepatotoxicity
In the ELOQUENT-2 trial (N=635), AST/ALT >3X the upper limit,
total bilirubin >2X the upper limit, and alkaline phosphatase
<2X the upper limit were 2.5% (ERd) vs 0.6% (Rd). Of 8 patients
experiencing hepatotoxicity, 2 patients discontinued treatment
while 6 patients had resolution and continued. Monitor liver
enzymes periodically. Stop EMPLICITI upon ≥Grade 3 elevation of
liver enzymes. Continuation of treatment may be considered after
return to baseline values.
Interference with Determination of Complete Response
EMPLICITI is a humanized IgG kappa monoclonal antibody that can
be detected on both the serum protein electrophoresis and
immunofixation assays used for the clinical monitoring of
endogenous M-protein. This interference can impact the
determination of complete response and possibly relapse from
complete response in patients with IgG kappa myeloma protein.
Pregnancy/Females and Males of Reproductive Potential
There are no available data on EMPLICITI use in pregnant women
to inform a drug-associated risk of major birth defects and
miscarriage.
There is a risk of fetal harm, including severe life-threatening
human birth defects, associated with lenalidomide and pomalidomide,
and they are contraindicated for use in pregnancy. Refer to the
respective product full prescribing information for requirements
regarding contraception and the prohibitions against blood and/or
sperm donation due to presence and transmission in blood and/or
semen and for additional information.
Adverse Reactions
ELOQUENT-2 trial:
- Serious adverse reactions were 65% (ERd) and 57% (Rd). The most
frequent serious adverse reactions in the ERd arm compared to the
Rd arm were: pneumonia (15%, 11%), pyrexia (7%, 5%), respiratory
tract infection (3.1%, 1.3%), anemia (2.8%, 1.9%), pulmonary
embolism (3.1%, 2.5%), and acute renal failure (2.5%, 1.9%).
- The most common adverse reactions in ERd and Rd, respectively
(≥20%) were fatigue (62%, 52%), diarrhea (47%, 36%), pyrexia (37%,
25%), constipation (36%, 27%), cough (34%, 19%), peripheral
neuropathy (27%, 21%), nasopharyngitis (25%, 19%), upper
respiratory tract infection (23%, 17%), decreased appetite (21%,
13%), and pneumonia (20%, 14%).
ELOQUENT-3 trial:
- Serious adverse reactions were 22% (EPd) and 15% (Pd). The most
frequent serious adverse reactions in the EPd arm compared to the
Pd arm were: pneumonia (13%, 11%) and respiratory tract infection
(7%, 3.6%).
- The most common adverse reactions in EPd arm (≥20% EPd) and Pd,
respectively, were constipation (22%, 11%) and hyperglycemia (20%,
15%).
Please see the full Prescribing Information.
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 and Facebook.
About AbbVie in Oncology
At AbbVie, we strive to discover and develop medicines that
deliver transformational improvements in cancer treatment by
uniquely combining our deep knowledge in core areas of biology with
cutting-edge technologies, and by working together with our
partners – scientists, clinical experts, industry peers, advocates,
and patients. We remain focused on delivering these transformative
advances in treatment across some of the most debilitating and
widespread cancers. We are also committed to exploring solutions to
help patients obtain access to our cancer medicines. With the
acquisitions of Pharmacyclics in 2015 and Stemcentrx in 2016, our
research and development efforts, and through collaborations,
AbbVie's oncology portfolio now consists of marketed medicines and
a pipeline containing multiple new molecules being evaluated
worldwide in more than 200 clinical trials and more than 20
different tumor types. For more information, please visit
http://www.abbvie.com/our-science/therapeutic-focus-areas/oncology.html.
Bristol-Myers Squibb Forward-Looking Statement
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, whether Empliciti for the 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.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20190827005768/en/
Bristol-Myers Squibb Company Media Inquiries:
Kirby Hosea 609-302-4399 kirby.hosea@bms.com
Investors: Tim Power 609-252-7509
timothy.power@bms.com
Bristol Myers Squibb (NYSE:BMY)
Historical Stock Chart
Von Feb 2024 bis Mär 2024
Bristol Myers Squibb (NYSE:BMY)
Historical Stock Chart
Von Mär 2023 bis Mär 2024