First and only immunostimulatory antibody
approved in the European Union for multiple myeloma
Accelerated assessment and approval based on
long-term data from ELOQUENT-2, which evaluated Empliciti in
combination with Revlimid® (lenalidomide) and
dexamethasone (Rd)
ELOQUENT-2 demonstrated the Empliciti
combination delivered a 53% relative improvement in
progression-free survival vs. Rd alone at three years (23% vs.
15%)
Bristol-Myers Squibb Company (NYSE:BMY) and AbbVie (NYSE:ABBV)
announced today that the European Commission has approved
Empliciti™ (elotuzumab) for the treatment of multiple myeloma as
combination therapy with Revlimid® (lenalidomide) and dexamethasone
in patients who have received at least one prior therapy. Empliciti
is now the first and only immunostimulatory antibody approved for
multiple myeloma in the European Union (EU).
The approval is based on data from the randomized, open-label,
Phase 3 ELOQUENT-2 study, which evaluated Empliciti in combination
with lenalidomide and dexamethasone (ERd) versus lenalidomide and
dexamethasone (Rd) alone. The co-primary endpoints of this study,
progression-free survival (PFS) as assessed by hazard ratio (HR)
and overall response rate (ORR), were achieved, with extended
follow-up data showing a 53% relative improvement in PFS rate at
three years (23% versus 15%). Additionally, a pre-specified interim
analysis for overall survival (OS) found a positive trend favoring
the Empliciti combination versus Rd alone (HR=0.77 [95% CI: 0.61,
0.97, p=0.0257]), though at the time of the interim analysis, the
OS endpoint had not reached the pre-determined threshold for
statistical significance. Patients will continue to be followed for
survival, and the final analysis is pending. Empliciti with
lenalidomide and dexamethasone 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 detailed
Important Safety Information below.
“At Bristol-Myers Squibb, we are committed to delivering
pioneering medicines with the goal of revolutionizing the way
cancer is treated for patients who inspire our work each and every
day,” said Emmanuel Blin, senior vice president and head of
Commercialization, Policy and Operations, Bristol-Myers Squibb.
“With the approval of Empliciti in the EU, we are proud to extend
our Immuno-Oncology science to multiple myeloma patients in Europe
who have received at least one prior therapy.”
In ELOQUENT-2, Empliciti was evaluated in patients who had
received one to three prior therapies. The study demonstrated that
the ERd regimen resulted in a 32% reduction in the risk of disease
progression or death compared to Rd alone (HR=0.68 [97.61% CI:
0.55, 0.85, p=0.0001]). The ERd regimen also showed a 21% relative
improvement in PFS rate at one year (68% versus 56%) and a 50%
relative improvement in PFS rate at two years (39% versus 26%)
compared to Rd alone. The ERd regimen demonstrated a significant
improvement in ORR of 78.5% (95% CI: 73.6-82.9; p=0.0002) versus
65.5% in the Rd arm (95% CI: 60.1-70.7). The extended follow-up
analysis also showed ERd had a median delay of one year in the time
to next treatment compared to Rd alone: 33.35 months (95% CI:
26.15, 40.21) versus 21.22 months (95% CI: 18.07, 23.20) (HR=0.62
[95% CI: 0.50, 0.77]). These data were initially reported at the
57th American Society of Hematology Annual Meeting in December
2015.
The most common adverse reactions (all grades) in ERd and Rd
(>10%), respectively, were diarrhea (59.2%, 49.3%), pyrexia
(43.0%, 27.7%), fatigue (40.0%, 34.7%), cough (33.2%, 20.3%),
nasopharyngitis (29.5%, 27.7%), upper respiratory tract infection
(25.2%, 22.7%), lymphopenia (17.6%, 13.6%), headache (17.2%, 9.6%),
pneumonia (15.6%, 12.9%) and herpes zoster (10.0%, 5.7%).
“Today’s decision of the European Commission is excellent news
for relapsed and refractory multiple myeloma patients,” said Sarper
Diler, President of Myeloma Patients Europe. “Multiple myeloma has
had a difficult-to-treat history, and at Myeloma Patients Europe,
we are committed to ensuring these patients living in any European
country are able to access new, innovative medicines, like
Empliciti.”
“Empliciti represents an important new treatment option for
patients with multiple myeloma and healthcare providers who are
treating this cancer in Europe,” said Michael Severino, M.D.,
executive vice president of research and development and chief
scientific officer, AbbVie. “AbbVie is proud to be part of the team
that developed Empliciti and pleased to be partnering with
Bristol-Myers Squibb to bring this new therapy to previously
treated multiple myeloma patients.”
About ELOQUENT-2
ELOQUENT-2 (CA204-004) is a Phase 3, open-label, randomized
study evaluating Empliciti in combination with Rd versus Rd alone
in patients with relapsed or refractory multiple myeloma. The trial
randomized 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.
“As multiple myeloma is largely incurable and is often
characterized by a cycle of remission and relapse, there is a
critical need for new therapies for patients that work in unique
and innovative ways,” said Antonio Palumbo, M.D., study
investigator and chief of the Myeloma Unit, Department of Oncology,
University of Torino in Torino, Italy. “In clinical trials,
Empliciti in combination with lenalidomide and dexamethasone
delivered a significant benefit in progression-free survival
compared to lenalidomide and dexamethasone alone, which could make
a meaningful difference in the lives of patients struggling with
this serious disease.”
Discontinuation rates due to adverse reactions were similar
across the ERd and Rd arms (8.7%, 12.9%). The most frequent serious
adverse reactions (Grade 3-4) in ERd and Rd were lymphopenia
(12.7%, 7.4%), pneumonia (10.5%, 8.1%), fatigue (6.4%, 6.2%),
diarrhea (3.7%, 3.1%) and deep vein thrombosis (3.5%, 1.7%). The
most common adverse reactions in ERd and Rd (>20%),
respectively, were diarrhea (59.2%, 49.3%), pyrexia (43.0%, 27.7%),
fatigue (40.0%, 34.7%), cough (33.2%, 20.3%), nasopharyngitis
(29.5%, 27.7%) and upper respiratory tract infection (25.2%,
22.7%).
Infusion reactions occurred in 10% of patients treated with ERd;
these adverse reactions were Grade 3 or lower (Grade 3, 1%; Grade
4, 0%). 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.
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. Patients often experience a cycle of remission and
relapse, and once a patient first relapses, their prognosis worsens
with progressively faster relapses through each subsequent line of
therapy. 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.
Bristol-Myers Squibb &
Immuno-Oncology: Advancing Oncology Research
At Bristol-Myers Squibb, we have a vision for the future of
cancer care that is focused on Immuno-Oncology, now considered a
major treatment modality alongside surgery, radiation and
chemotherapy for certain types of cancer.
We have a comprehensive clinical portfolio of investigational
and approved Immuno-Oncology agents, many of which were discovered
and developed by our scientists. We pioneered the research leading
to the first regulatory approval for the combination of two
Immuno-Oncology agents and continue to study the role of
combinations in cancer.
Our collaboration with academia, as well as small and large
biotech companies, is responsible for researching the potential
Immuno-Oncology and non-Immuno-Oncology combinations, with the goal
of providing new treatment options in clinical practice.
At Bristol-Myers Squibb, we are committed to changing survival
expectations in hard-to-treat cancers and the way patients live
with cancer.
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 in combination with lenalidomide and dexamethasone is
approved in the United States, and the safety and efficacy of
Empliciti is being evaluated by other health authorities.
Bristol-Myers Squibb and AbbVie are co-developing Empliciti,
with Bristol-Myers Squibb solely responsible for commercial
activities.
U.S. 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.
U.S. 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
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,
2015 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 2015 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. All
other trademarks are property of their respective owners.
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609-252-5894william.szablewski@bms.com
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