Positive opinion based on reduction in the risk of disease
progression or death with Empliciti in combination with
standard of care regimen for multiple myeloma demonstrated in ELOQUENT-2
study
Bristol-Myers
Squibb Company (NYSE:BMY) and AbbVie (NYSE:ABBV) today announced
that the Committee for Medicinal Products for Human Use (CHMP) of the
European Medicines Agency (EMA) has adopted a positive opinion
recommending that Empliciti (elotuzumab), an investigational
immunostimulatory antibody, be granted approval for the treatment of
multiple myeloma as combination therapy with Revlimid®
(lenalidomide) and dexamethasone in patients who have received at least
one prior therapy. The application now will be reviewed by the European
Commission, which has the authority to approve medicines for the
European Union (EU).
“Today’s positive CHMP recommendation means we are one step closer to
offering a new type of treatment for patients in Europe with multiple
myeloma who have received at least one prior therapy,” said Michael
Giordano, M.D., senior vice president, head of Development, Oncology,
Bristol-Myers Squibb. “We look forward to the European Commission’s
decision and the opportunity to extend our leading Immuno-Oncology
science to patients with multiple myeloma.”
The CHMP positive opinion is based on data from the Phase 3, open-label
ELOQUENT-2 study, which evaluated Empliciti in combination with
lenalidomide and dexamethasone (ERd) versus lenalidomide and
dexamethasone (Rd) alone. The results of this trial showed a 30%
reduction in the risk of disease progression or death with ERd compared
to Rd alone and, at the two year time point, ERd delivered a 52%
relative improvement in progression-free survival. 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%). These results were published in The New
England Journal of Medicine on June 2, 2015.
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 is also 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.
On November 30, 2015, the U.S. Food and Drug Administration approved Empliciti
in combination with lenalidomide and dexamethasone in patients with
multiple myeloma who have received one to three prior therapies. The
safety and efficacy of Empliciti is still being evaluated by
other health authorities.
Bristol-Myers Squibb and AbbVie are co-developing Empliciti, with
Bristol-Myers Squibb solely responsible for commercial activities.
About Multiple Myeloma
Multiple myeloma is a hematologic, or blood, cancer that develops in the
bone marrow. It occurs when a plasma cell, a type of cell in the soft
center of bone marrow, becomes cancerous and multiplies uncontrollably.
Common symptoms of multiple myeloma include bone pain, fatigue, kidney
impairment and infections.
Despite advances in multiple myeloma treatment over the last decade,
less than half of patients survive for five or more years after
diagnosis. A common characteristic for many patients is that they
experience a cycle of remission and relapse, in which they stop
treatment for a short time, but eventually return to a treatment shortly
after. It is estimated that annually, more than 114,200 new cases of
multiple myeloma are diagnosed and more than 80,000 people die from the
disease globally.
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 US full Prescribing Information 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 www.bms.com
or follow us on Twitter at http://twitter.com/bmsnews.
About AbbVie
AbbVie is a global, research-based biopharmaceutical company formed in
2013 following separation from Abbott Laboratories. The company's
mission is to use its expertise, dedicated people and unique approach to
innovation to develop and market advanced therapies that address some of
the world's most complex and serious diseases. Together with its
wholly-owned subsidiary, Pharmacyclics, AbbVie employs more than 28,000
people worldwide and markets medicines in more than 170 countries.
For further information on the company and its people, portfolio and
commitments, please visit www.abbvie.com.
Follow @abbvie on
Twitter or view careers on our Facebook or LinkedIn page.
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.
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, 2014 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.
Forward-Looking Statements
Some statements in this news release may be forward-looking
statements for purposes of the Private Securities Litigation Reform Act
of 1995. The words "believe," "expect," "anticipate," "project" and
similar expressions, among others, generally identify forward-looking
statements. AbbVie cautions that these forward-looking statements are
subject to risks and uncertainties that may cause actual results to
differ materially from those indicated in the forward-looking
statements. Such risks and uncertainties include, but are not limited
to, challenges to intellectual property, competition from other
products, difficulties inherent in the research and development process,
adverse litigation or government action, and changes to laws and
regulations applicable to our industry.
Additional information about the economic, competitive, governmental,
technological and other factors that may affect AbbVie's operations is
set forth in Item 1A, "Risk Factors," in AbbVie's 2014 Annual Report on
Form 10-K, which has been filed with the Securities and Exchange
Commission. AbbVie undertakes no obligation to release publicly any
revisions to forward-looking statements as a result of subsequent events
or developments, except as required by law.
Endnotes
Empliciti is a trademark of Bristol-Myers Squibb Company.
Revlimid is a registered trademark of Celgene Corporation.
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