- First and only immunostimulatory antibody approved for multiple myeloma
- Approval based on ELOQUENT-2, which established the combination of Empliciti with lenalidomide and dexamethasone (Rd) delivered a significant progression-free survival benefit vs. Rd alone, demonstrated over two years (HR 0.70 [95% CI: 0.57, 0.85; p = 0.0004])
Bristol-Myers
Squibb Company (NYSE:BMY) and AbbVie (NYSE:ABBV) today
announced the U.S. Food and Drug Administration (FDA) has approved Empliciti
(elotuzumab) for the treatment of multiple myeloma as combination
therapy with Revlimid® (lenalidomide) and dexamethasone (ERd)
in patients who have received one to three prior therapies. The approval
of this first and only immunostimulatory antibody for multiple myeloma
is based on data from the randomized, open-label, Phase 3, ELOQUENT-2
study, which demonstrated that the ERd regimen resulted in a 30%
reduction in the risk of disease progression or death compared to Rd
alone (HR 0.70 [95% CI: 0.57, 0.85; p = 0.0004]).
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The co-primary endpoints were progression-free survival (PFS), as
assessed by hazard ratio, and overall response rate (ORR). With a
minimum of two years follow-up, ERd delivered a benefit in PFS that was
maintained over time, with PFS rates of 68% versus 57% at one year and
41% versus 27% at two years in the ERd and Rd arms, respectively. The
ERd regimen also demonstrated a significant improvement in ORR,
achieving an ORR of 78.5% (95% CI: 73.6% to 82.9%) versus 65.5% in the
Rd arm (95% CI: 60.1% to 70.7%). 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%).
“At Bristol-Myers Squibb, we are leading a revolution in cancer
treatment that is changing expectations for patients with some of the
hardest-to-treat cancers. With today’s approval of Empliciti, we
are pleased to now bring the promise of our Immuno-Oncology research to
patients with multiple myeloma,” said Francis
Cuss, MB Bchir, FRCP, chief scientific officer, Bristol-Myers
Squibb. “Empliciti represents a fundamentally different approach
of directly activating the immune system in patients with relapsed or
refractory multiple myeloma, delivering improved outcomes for those in
need.”
Empliciti is available for injection for intravenous use in 300
mg and 400 mg vials. The company expects to begin shipping Empliciti within
the next 48 hours. Empliciti is also under review by the European
Medicines Agency and has been granted accelerated assessment.
Discontinuation rates due to adverse reactions were similar across the
ERd and Rd control arms (6.0% vs. 6.3%). ERd is associated with
the following Warnings and Precautions: Infusion Reactions, Infections,
Second Primary Malignancies, Hepatotoxicity, Interference with
Determination of Complete Response, Pregnancy/Females and Males of
Reproductive Potential, and Adverse Reactions. Please see the detailed
Important Safety Information and a link to the Prescribing Information
below.
“Multiple myeloma remains largely incurable, with only half of patients
surviving five years after diagnosis,” said Sagar Lonial, M.D., chief
medical officer of the Winship Cancer Institute of Emory University.
“The approval of elotuzumab (Empliciti) provides renewed hope for
the multiple myeloma community who urgently need a treatment option that
extends the time patients live without their disease progressing.”
"Empliciti in combination with lenalidomide and
dexamethasone is an important new option for patients with multiple
myeloma and healthcare providers who are treating this cancer," said
Michael Severino, M.D., executive vice president of research and
development and chief scientific officer, AbbVie. "AbbVie is pleased to
have partnered with Bristol-Myers Squibb in making this new treatment
available for patients with relapsed or refractory multiple myeloma."
About ELOQUENT-2
ELOQUENT-2 (CA204-004) is a randomized, open-label, Phase 3 study
evaluating Empliciti in combination with lenalidomide and
dexamethasone (ERd) versus lenalidomide and dexamethasone (Rd) alone in
patients with relapsed or refractory multiple myeloma. The trial
enrolled 646 patients who had received one to three prior therapies.
Patients were randomized 1:1 to receive either Empliciti 10 mg/kg
in combination with Rd or Rd alone in 4-week cycles until disease
progression or unacceptable toxicity. Baseline patient demographics and
disease characteristics were well balanced between treatment arms and
included a meaningful portion of patients who were ≥ 65 years old, had
high-risk cytogenetics, and/or were refractory to the most recent line
of therapy. The minimum follow-up for all study subjects was 24 months.
The co-primary endpoints were PFS, as assessed by hazard ratio, and ORR
as determined by a blinded Independent Review Committee using the
European Group for Blood and Marrow Transplantation response criteria.
Results of the ELOQUENT-2 study were published in The New England
Journal of Medicine on June 2, 2015.
The study demonstrated that the ERd regimen resulted in a 30% reduction
in the risk of disease progression or death compared to Rd alone (HR
0.70 [95% CI: 0.57, 0.85; p = 0.0004]). Additionally, the PFS rates in
the ERd arm versus the Rd arm were 68% versus 57% at one year and 41%
versus 27% at two years, respectively. The ERd regimen demonstrated a
significant improvement in ORR, achieving an ORR of 78.5% (95% CI, 73.6%
to 82.9%; p = 0.0002) in the ERd arm versus 65.5% in the Rd arm (95% CI,
60.1% to 70.7%). The median PFS in the ERd group was 19.4 months (95%
CI, 16.6 to 22.2) versus 14.9 months (95% CI, 12.1 to 17.2) in the Rd
group. At the time of the interim analysis, there were fewer deaths in
the ERd versus Rd study arm (94 [29%] versus 116 [36%], respectively).
Serious adverse reactions were reported in 65.4% of patients treated on
the ERd arm and 56.5% for patients treated on the Rd arm. 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%) are 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%). Infusion reactions occurred in 10% of patients treated with ERd;
these adverse events were Grade 3 or lower (Grade 3, 1%; Grade 4, 0%)
and were manageable. In the trial, 1% of patients discontinued due to
infusion reactions and 5% of patients required interruption of the
administration of Empliciti for a median of 25 minutes.
Grade 3/4 laboratory abnormalities that worsened from baseline and had a
10% or higher incidence for ERd patients and a 5% higher incidence than
Rd patients were: lymphopenia (76.7%, 48.7%), leukopenia (32.4%, 25.6%),
hyperglycemia (17.0%, 10.2%), and hypocalcemia (11.3% and 4.7%).
Overall, the proportion of patients who discontinued treatment due to
adverse reactions was similar for the ERd and Rd arms (6.0% vs. 6.3%,
respectively).
“The approval of Empliciti is an innovative advancement in the
treatment of multiple myeloma,” said Walter M. Capone, chief executive
officer and president, The Multiple Myeloma Research Foundation. “This
is an exciting opportunity for patients who experience relapse and may
benefit from this new immunotherapy treatment."
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.
Bristol-Myers Squibb and AbbVie are co-developing Empliciti, with
Bristol-Myers Squibb solely responsible for commercial activities. Prior
to approval, Empliciti was granted Breakthrough Therapy
Designation by the FDA for use in combination with lenalidomide and
dexamethasone for the treatment of multiple myeloma in patients who have
received one to three prior therapies. According to the FDA,
Breakthrough Therapy Designation is intended to expedite the development
and review of drugs for serious or life-threatening conditions. The
criteria for Breakthrough Therapy Designation requires preliminary
clinical evidence that demonstrates the drug may have substantial
improvement on at least one clinically significant endpoint over
available therapy.
About Bristol-Myers Squib’s Patient
Support Programs
Bristol-Myers Squibb is committed to helping patients through treatment
with Empliciti. For support and assistance, patients and
physicians may call 1-844-EMPLICITI. This number offers one-stop
access to a range of support services for patients and healthcare
professionals alike.
About Bristol-Myers Squibb’s Access Support
Bristol-Myers Squibb is committed to helping patients access Empliciti
and offers numerous programs to support patients and providers in
gaining access. BMS Access Support®, the Bristol-Myers Squibb
Reimbursement Services program, is designed to support access to BMS
medicines and expedite time to therapy through reimbursement support
including Benefit Investigations, Prior Authorization Facilitation,
Appeals Assistance, and assistance for patient out-of-pocket costs. BMS
Access Support assists patients and providers throughout the treatment
journey―whether it is at initial diagnosis or in support of transition
from a clinical trial. More information about our reimbursement support
services can be obtained by calling 1-800-861-0048 or by visiting www.bmsaccesssupport.com.
For healthcare providers seeking Empliciti specific reimbursement
information, please visit the BMS Access Support Product section by
visiting www.bmsaccesssupportoncology.com.
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.
EMPLICITI (elotuzumab) INDICATIONS & IMPORTANT SAFETY INFORMATION
INDICATION
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 Reaction
-
In a clinical trial of patients with multiple myeloma (n=365),
EMPLICITI caused 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
-
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
-
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%)
are 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 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.
AbbVie 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. BMS
Access Support is a registered trademark of Bristol-Myers Squibb Company.
Revlimid is a registered trademark of Celgene Corporation.
© 2015 Bristol-Myers Squibb Company. All rights reserved.
Bristol-Myers Squibb CompanyMedia:Audrey Abernathy, 609-419-5375cell: 919-605-4521audrey.abernathy@bms.comorInvestors:Ranya Dajani, 609-252-5330ranya.dajani@bms.comorBill Szablewski, 609-252-5894william.szablewski@bms.com