Bristol-Myers Squibb Company (NYSE: BMY) today announced that
the European Medicines Agency (EMA) has validated the Company’s
type II variation application for Empliciti (elotuzumab) in
combination with pomalidomide and low-dose dexamethasone (EPd) for
the treatment of adult patients with 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. Validation of the application
confirms the submission is complete and begins the EMA’s
centralized review process.
“Given the need for new treatment options for patients with
multiple myeloma, we look forward to working closely with the EMA
as they review this application,” said Fouad Namouni, M.D., head,
oncology development, Bristol-Myers Squibb. “It is our hope that
this new Empliciti-based combination will soon become available for
patients in the European Union with multiple myeloma, whose disease
progressed on lenalidomide and a PI.”
The application is based on data from ELOQUENT-3, a randomized
Phase 2 study evaluating the EPd combination versus pomalidomide
and dexamethasone (Pd) alone in patients with relapsed or
refractory multiple myeloma (RRMM). Data from this study were
presented at the 23rd Congress of the European Hematology
Association in June.
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 PI. 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 at the dose of 10 mg/kg
IV weekly for the first 2 cycles and 20 mg/kg monthly starting from
cycle 3. Patients randomized to EPd experienced a 46% reduction in
risk of disease progression (HR 0.54; 95% CI: 0.34 to 0.86,
p=0.0078) compared with patients randomized to Pd alone, with
median PFS, the study’s primary endpoint, of 10.3 months (95% CI:
5.6 to not estimable) compared with 4.7 months (95% CI: 2.8 to 7.2)
in Pd patients. The PFS benefit experienced among patients
randomized to EPd was consistent among patients who had received
two to three prior lines of therapy (HR 0.55; 95% CI: 0.31 to 0.98)
and four or more prior lines of therapy (HR 0.51; CI 95%: 0.24 to
1.08).
Rates of treatment-related hematologic adverse events (AEs) were
comparable between EPd and Pd groups (38% and 42%, respectively).
The most commonly occurring hematologic AEs among patients
receiving EPd were neutropenia (13%), anemia (10%),
thrombocytopenia (8%) and lymphopenia (8%). AEs led to
discontinuation in 18% of patients in the EPd arm, compared with
24% of patients in the Pd arm.
Bristol-Myers Squibb &
Immuno-Oncology: Advancing Oncology Research
At Bristol-Myers Squibb, patients are at the center of
everything we do. Our vision for the future of cancer care is
focused on researching and developing transformational medicines,
including Immuno-Oncology (I-O) therapeutic approaches, for
hard-to-treat cancers that could potentially improve outcomes for
these patients.
We are leading the integrated scientific understanding of both
tumor cell and immune system pathways, through our extensive
portfolio of investigational compounds and approved agents. Our
differentiated clinical development program is studying broad
patient populations across more than 50 types of cancers with 24
clinical-stage molecules designed to target different immune system
pathways. Our deep expertise and innovative clinical trial designs
position us to advance the I-O/I-O, I-O/chemotherapy, I-O/targeted
therapies and I-O/radiation therapies across multiple tumors and
potentially deliver the next wave of therapies with a sense of
urgency. We also continue to pioneer research that will help
facilitate a deeper understanding of the role of immune biomarkers
and how a patient’s tumor biology can be used as a guide for
treatment decisions throughout their journey.
We understand making the promise of transformational medicines
like I-O therapies a reality for the many patients who may benefit
from these therapies requires not only innovation on our part but
also close collaboration with leading experts in the field. Our
partnerships with academia, government, advocacy and biotech
companies support our collective goal of providing new treatment
options to advance the standards of clinical practice.
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 acts through multiple mechanisms-of-action. It
directly activates the immune system through Natural Killer cells
via the SLAMF7 pathway. Empliciti targets SLAMF7 on myeloma cells,
tagging these malignant cells for Natural Killer cell-mediated
destruction via antibody-dependent cellular toxicity. Empliciti
also promotes macrophage-mediated antibody-dependent cellular
phagocytosis (ADCP) of myeloma cells.
U.S. FDA-APPROVED INDICATION FOR
EMPLICITI ™
EMPLICITI™ (elotuzumab) is indicated in combination with
lenalidomide and dexamethasone for the treatment of patients with
multiple myeloma who have received one to three prior
therapies.
IMPORTANT SAFETY
INFORMATION
Infusion Reactions
- EMPLICITI can cause infusion reactions.
Common symptoms include 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. 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 infusing with
EMPLICITI.
Infections
- In a clinical trial of patients with
multiple myeloma (N=635), infections were reported in 81.4% of
patients in the EMPLICITI with lenalidomide/dexamethasone arm (ERd)
and 74.4% in the lenalidomide/dexamethasone arm (Rd). Grade 3-4
infections were 28% (ERd) and 24.3% (Rd). Opportunistic infections
were reported in 22% (ERd) and 12.9% (Rd). Fungal infections were
9.7% (ERd) and 5.4% (Rd). Herpes zoster was 13.5% (ERd) and 6.9%
(Rd). Discontinuations due to infections were 3.5% (ERd) and 4.1%
(Rd). Fatal infections were 2.5% (ERd) and 2.2% (Rd). Monitor
patients for development of infections and treat promptly.
Second Primary Malignancies
- In a clinical trial of patients with
multiple myeloma (N=635), invasive second primary malignancies
(SPM) were 9.1% (ERd) and 5.7% (Rd). The rate of hematologic
malignancies were 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). Monitor
patients for the development of SPMs.
Hepatotoxicity
- Elevations in liver enzymes (AST/ALT
greater than 3 times the upper limit, total bilirubin greater than
2 times the upper limit, and alkaline phosphatase less than 2 times
the upper limit) consistent with hepatotoxicity were 2.5% (ERd) and
0.6% (Rd). Two patients experiencing hepatotoxicity discontinued
treatment; however, 6 out of 8 patients had resolution and
continued treatment. Monitor liver enzymes periodically. Stop
EMPLICITI upon Grade 3 or higher elevation of liver enzymes. After
return to baseline values, continuation of treatment may be
considered.
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 studies with EMPLICITI
with pregnant women to inform any drug associated risks.
- There is a risk of fetal harm,
including severe life-threatening human birth defects associated
with lenalidomide and it is contraindicated for use in pregnancy.
Refer to the lenalidomide 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
- Infusion reactions were reported in
approximately 10% of patients treated with EMPLICITI with
lenalidomide and dexamethasone. All reports of infusion reaction
were Grade 3 or lower. Grade 3 infusion reactions occurred in 1% of
patients.
- Serious adverse reactions were 65.4%
(ERd) and 56.5% (Rd). The most frequent serious adverse reactions
in the ERd arm compared to the Rd arm were: pneumonia (15.4%, 11%),
pyrexia (6.9%, 4.7%), 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 (61.6%, 51.7%),
diarrhea (46.9%, 36.0%), pyrexia (37.4%, 24.6%), constipation
(35.5%, 27.1%), cough (34.3%, 18.9%), peripheral neuropathy (26.7%,
20.8%), nasopharyngitis (24.5%, 19.2%), upper respiratory tract
infection (22.6%, 17.4%), decreased appetite (20.8%, 12.6%), and
pneumonia (20.1%, 14.2%).
Please see the full Prescribing Information
for EMPLICITI.
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/oncology.
Bristol-Myers Squibb Forward-Looking Statement
This press release contains "forward-looking statements" as that
term is defined in the Private Securities Litigation Reform Act of
1995 regarding the research, development and commercialization of
pharmaceutical products. Such forward-looking statements are based
on current expectations and involve inherent risks and
uncertainties, including factors that could delay, divert or change
any of them, and could cause actual outcomes and results to differ
materially from current expectations. No forward-looking statement
can be guaranteed. Among other risks, there can be no guarantee
that Empliciti will receive regulatory approval for the indications
described herein. 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,
2017 in our Quarterly Reports on Form 10-Q and our Current Reports
on Form 8-K. Bristol-Myers Squibb undertakes no obligation to
publicly update any forward-looking statement, whether as a result
of new information, future events or otherwise.
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Bristol-Myers SquibbMedia:Danielle Halstrom,
215-280-2898danielle.halstrom@bms.comorInvestor:Bill
Szablewski, 609-252-5894william.szablewski@bms.comorTim Power,
609-252-7509timothy.power@bms.com
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