In a descriptive analysis, addition of
Empliciti to pomalidomide and dexamethasone reduced risk of
death by 46% among patients with RRMM
Empliciti-based combination showed
improvements across efficacy endpoints, including continued
progression-free survival benefit at 18 months
Bristol-Myers Squibb Company (NYSE: BMY) today announced the
presentation of updated data from ELOQUENT-3, the international
randomized Phase 2 study evaluating Empliciti (elotuzumab) plus
pomalidomide and dexamethasone (EPd) versus pomalidomide and
dexamethasone (Pd) alone in patients with relapsed or refractory
multiple myeloma (RRMM). In a non-prespecified analysis conducted
to provide a descriptive assessment of overall survival (OS) after
extended follow-up of at least 18.3 months, patients treated with
EPd continued to experience sustained and clinically relevant OS
and progression-free survival (PFS) benefits compared with patients
treated with Pd.
Treatment with EPd was associated with a 46% reduction in risk
of death [Hazard Ratio (HR) 0.54; 95% Confidence Interval (CI):
0.30 to 0.96] versus treatment with Pd alone. At 18 months, rates
of OS, a secondary endpoint, were 68% for patients treated with EPd
compared to 49% for patients treated with Pd. Median OS was not
reached with EPd [95% CI: 24.9 months, Not Estimable (NE)] at the
time of analysis and was 17.4 months (95% CI: 13.8, NE) among
patients receiving Pd. Eighteen-month PFS rates were 34% among
patients randomized to EPd compared to 11% among patients
randomized to Pd. Safety results for EPd were consistent with the
primary analysis and with prior findings for Empliciti and
pomalidomide regimens.
These data will be presented at the 24th Congress of the
European Hematology Association (EHA) in Amsterdam in a poster
display (Abstract #PS1370) on Saturday, June 15 from 5:30-7 PM
CEST.
“Multiple myeloma is a disease characterized by relapse, making
it all the more important to have effective options available for
patients after initial treatments. With 18 months of follow-up from
the ELOQUENT-3 trial, we continue to see meaningful improvements
across key endpoints with EPd versus Pd alone, including a positive
trend in overall survival,” said Meletios A. Dimopoulos, M.D.,
professor and chairman of the Department of Clinical Therapeutics
at Kapodistrian University of Athens School of Medicine. “These
data point to the potential for this combination to become a new
standard of care for patients with multiple myeloma that returned
after or did not respond to prior therapies, including lenalidomide
and a proteasome inhibitor.”
“The extended follow-up results from ELOQUENT-3 reinforce the
EPd combination’s sustained efficacy and favorable safety profile
in patients with relapsed or refractory multiple myeloma,” said
Fouad Namouni, M.D., head, Oncology Development, Bristol-Myers
Squibb. “These data, along with our overall presence at EHA,
underscore our commitment to leading innovative research in
hematology and developing therapies that can improve long-term
survival for patients with different types of blood cancer.”
Data from the primary analysis of ELOQUENT-3 were published in
the New England Journal of Medicine in November 2018 and supported
the approval of EPd by the U.S. Food and Drug Administration for
the treatment of adult patients with RRMM who have received at
least two prior therapies, including lenalidomide and a proteasome
inhibitor.
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 RRMM
who received two or more prior therapies and were either refractory
or relapsed and refractory to lenalidomide and a proteasome
inhibitor. Patients were randomized 1:1 to receive either EPd
(n=60) or Pd (n=57) in 28-day cycles until disease progression or
unacceptable toxicity. Patients in both the EPd and Pd arms
received 4 mg of pomalidomide for days 1-21 of each cycle, and the
weekly equivalent of 40 mg or 20 mg dexamethasone for patients ≤75
years or >75 years, respectively. In the EPd arm, Empliciti was
administered intravenously at the dose of 10 mg/kg weekly for the
first 2 cycles and 20 mg/kg every four weeks starting from cycle 3.
The primary endpoint of the study was investigator-assessed
PFS.
In the 18-month follow-up analysis, adverse events (AEs) were
comparable between treatment arms and consistent with the primary
analysis. The most common grade 3-4 AEs were infections (22% among
patients receiving EPd, 24% among patients receiving Pd),
neutropenia (13%, 29%), anemia (10%, 22%), thrombocytopenia (10%,
7%) and hyperglycemia (8%, 11%). Grade 5 all-cause AEs occurred in
seven patients (12%) who received EPd and nine patients (16%) who
received Pd.
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 for the treatment
of patients with multiple myeloma who have received one to three
prior therapies.
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 https://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, 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 Empliciti may not receive
regulatory approval for the additional indication described in this
release and, if approved, whether Empliciti will be commercially
successful for the additional indication described in this release.
No forward-looking statement can be guaranteed. Forward-looking
statements in this press release should be evaluated together with
the many uncertainties that affect Bristol-Myers Squibb's business,
particularly those identified in the cautionary 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 federal
securities 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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Bristol-Myers Squibb CompanyMedia Inquiries:Kirby
Hosea609-302-4399kirby.hosea@bms.comORJessica
Horton609-577-5644jessica.horton@bms.comInvestors:Tim
Power609-252-7509timothy.power@bms.com
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