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U.S. Food and Drug Administration Accepts for Priority Review Bristol-Myers Squibb's Application for Empliciti (elotuzumab) Plus Pomalidomide and Low-Dose Dexamethasone in Patients with Relapsed or Refractory Multiple Myeloma

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Application based on results from Phase 2 ELOQUENT-3 study

Bristol-Myers
Squibb Company
(NYSE:BMY) today announced that the U.S. Food and
Drug Administration (FDA) accepted its supplemental Biologics License
Application (sBLA) for Empliciti (elotuzumab) in combination with
pomalidomide and low-dose dexamethasone (EPd) for the treatment of
patients with relapsed/refractory multiple myeloma (RRMM) who have
received at least two prior therapies, including lenalidomide and a
proteasome inhibitor. The FDA granted the application priority review
with an action date of December 27, 2018.

"This file acceptance is an important step in BMS's ongoing efforts to
advance treatment options for patients with relapsed/refractory multiple
myeloma," said Jeffrey Jackson, Ph.D., hematology development lead,
Bristol-Myers Squibb. "Given the need for new, effective treatment
options in this patient population, we look forward to working with the
FDA with the hope of bringing this combination to patients with RRMM
whose disease progressed on previous therapies as quickly as possible."

The application is based on data from ELOQUENT-3, a randomized Phase 2
study evaluating the addition of Empliciti to pomalidomide and
low-dose dexamethasone in patients with 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,
elotuzumab 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). The safety profile for EPd was consistent with
prior findings for Empliciti and pomalidomide regimens.

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 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.

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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