FDA Grants Approval for BAVENCIO® (avelumab), the First Immunotherapy Approved for Metastatic Merkel Cell Carcinoma

Darmstadt, Germany and New York (ots/PRNewswire) -

Not intended for UK-based media

- Only FDA-approved treatment for metastatic Merkel cell carcinoma, a
rare and aggressive skin cancer
- First indication for BAVENCIO, a human anti-PD-L1 antibody

Merck and Pfizer Inc. (NYSE: PFE) today announced that the US Food
and Drug Administration (FDA) has approved BAVENCIO® (avelumab)
Injection 20 mg/mL, for intravenous use, for the treatment of adults
and pediatric patients 12 years and older with metastatic Merkel cell
carcinoma (mMCC). This indication is approved under accelerated
approval based on tumor response and duration of response. Continued
approval for this indication may be contingent upon verification and
description of clinical benefit in confirmatory trials.[1] BAVENCIO
will be co-commercialized by EMD Serono, the biopharmaceutical
business of Merck in the US and Canada, and Pfizer. BAVENCIO was
developed, reviewed and approved through the FDA's Breakthrough
Therapy Designation and Priority Review programs.

BAVENCIO, a human anti-PD-L1 antibody, is the first FDA-approved
therapy for patients with mMCC.[2] Metastatic MCC is a rare and
aggressive skin cancer, with fewer than half of patients surviving
more than one year and fewer than 20% surviving beyond five years.[3]

"At the heart of this FDA approval is our drive to make a
meaningful difference for patients with hard-to-treat cancers like
metastatic Merkel cell carcinoma," said Belén Garijo, CEO Healthcare
and Member of the Executive Board of Merck. "BAVENCIO's journey has
included years of hard work - from the scientists who discovered this
molecule in our labs, to our alliance with Pfizer and to the study
participants and investigators worldwide. We are grateful to all who
have made it possible for us to bring this important new treatment
option to patients."

"Today is a significant milestone for people fighting metastatic
Merkel cell carcinoma, who until now have not had any options beyond
chemotherapy," said Albert Bourla, Group President, Pfizer Innovative
Health. "This approval demonstrates the power of collaboration to
accelerate meaningful new choices for cancer patients."

"Merkel cell carcinoma is rarer than some of the more well-known
skin cancers, however, it's very aggressive and the proportion of
people who die from MCC is much higher than that of people with
melanoma," said Deborah S. Sarnoff, MD, President of the Skin Cancer
Foundation. "With this approval, I believe there is new hope for
people and their families touched by this rare form of skin cancer."

The efficacy and safety of BAVENCIO was demonstrated in the
JAVELIN Merkel 200 trial, an open-label, single-arm, multi-center
study conducted in 88 patients with histologically confirmed
metastatic MCC whose disease had progressed on or after chemotherapy
administered for distant metastatic disease. Sixty-five percent of
patients were reported to have had one prior anti-cancer therapy for
metastatic MCC and 35% had two or more prior therapies. The major
efficacy outcome measures were confirmed overall response rate (ORR)
according to Response Evaluation Criteria in Solid Tumors (RECIST)
v1.1 as assessed by a blinded independent central review committee
(IRC) and IRC-assessed duration of response.

The overall response rate (ORR) was 33% (95% confidence interval
[CI]: 23.3-43.8%).[1] Eleven percent of patients experienced a
complete response (95% CI: 6.6-19.9%) and 22% of patients experienced
a partial response (95% CI: 13.5-31.7%). Tumor responses were
durable, with 86% of responses lasting for at least six months
(n=25).[1] Forty-five percent of responses lasted at least 12 months
(n=13).[1] Duration of response ranged from 2.8 to over 23.3 months.

The warnings and precautions for BAVENCIO include immune-mediated
adverse reactions (such as pneumonitis, hepatitis, colitis,
endocrinopathies, nephritis and renal dysfunction, and other adverse
reactions), infusion-related reactions and embryo-fetal toxicity. The
most common adverse reactions (reported in at least 20% of patients)
included fatigue (50%), musculoskeletal pain (32%), diarrhea (23%),
nausea (22%), infusion-related reactions (22%), rash (22%), decreased
appetite (20%) and peripheral edema (20%).[1] For more information,
please see Important Safety Information for BAVENCIO below.

BAVENCIO is designed to potentially engage both the adaptive and
innate immune systems. By binding to PD-L1, BAVENCIO is thought to
prevent tumor cells from using PD-L1 for protection against white
blood cells, such as T-cells, exposing them to anti-tumor
responses.[1] BAVENCIO has been shown to induce antibody-dependent
cell-mediated cytotoxicity (ADCC) in vitro.[1]

BAVENCIO is available for order now in the US. The alliance is
committed to providing industry-leading patient access and
reimbursement support through its CoverOne(TM) program in the US.
This program provides a spectrum of patient access and reimbursement
support services intended to help patients receive appropriate access
to BAVENCIO in the United States.

About JAVELIN Merkel 200

The efficacy and safety of BAVENCIO was demonstrated in the
JAVELIN Merkel 200 trial, an open-label, single-arm, multi-center
study conducted in 88 patients with histologically confirmed
metastatic MCC whose disease had progressed on or after chemotherapy
administered for distant metastatic disease. Sixty-five percent of
patients were reported to have had one prior anti-cancer therapy for
metastatic MCC and 35% had two or more prior therapies. The major
efficacy outcome measures were confirmed overall response rate (ORR)
according to Response Evaluation Criteria in Solid Tumors (RECIST)
v1.1 as assessed by a blinded independent central review committee
(IRC) and IRC-assessed duration of response.

The trial excluded patients with autoimmune disease; medical
conditions requiring systemic immunosuppression; prior organ or
allogenic stem cell transplantation; prior treatment with anti-PD-1,
anti-PD-L1 or anti-CTLA-4 antibodies; CNS metastases; infection with
HIV, hepatitis B or hepatitis C; or ECOG performance score greater
than or equal to two. Patients received BAVENCIO 10 mg/kg as an
intravenous infusion over 60 minutes every two weeks until disease
progression or unacceptable toxicity.

The international clinical development program for avelumab, known
as JAVELIN, involves at least 30 clinical programs, including nine
Phase III trials, and more than 4,000 patients across more than 15
tumor types. In October 2016, the alliance announced the European
Medicines Agency accepted the Marketing Authorisation Application for
avelumab for the proposed indication of metastatic MCC.

IMPORTANT SAFETY INFORMATION and INDICATION

BAVENCIO can cause immune-mediated pneumonitis, including fatal
cases. Monitor patients for signs and symptoms of pneumonitis and
evaluate suspected cases with radiographic imaging. Administer
corticosteroids for Grade 2 or greater pneumonitis. Withhold BAVENCIO
for moderate (Grade 2) and permanently discontinue for severe (Grade
3), life-threatening (Grade 4), or recurrent moderate (Grade 2)
pneumonitis. Pneumonitis occurred in 1.2% (21/1738) of patients,
including one (0.1%) patient with Grade 5, one (0.1%) with Grade 4,
and five (0.3%) with Grade 3.

BAVENCIO can cause immune-mediated hepatitis, including fatal
cases. Monitor patients for abnormal liver tests prior to and
periodically during treatment. Administer corticosteroids for Grade 2
or greater hepatitis. Withhold BAVENCIO for moderate (Grade 2)
immune-mediated hepatitis until resolution and permanently
discontinue for severe (Grade 3) or life-threatening (Grade 4)
immune-mediated hepatitis. Immune-mediated hepatitis was reported in
0.9% (16/1738) of patients, including two (0.1%) patients with Grade
5 and 11 (0.6 %) with Grade 3.

BAVENCIO can cause immune-mediated colitis. Monitor patients for
signs and symptoms of colitis. Administer corticosteroids for Grade 2
or greater colitis. Withhold BAVENCIO until resolution for moderate
or severe (Grade 2 or 3) colitis and permanently discontinue for
life-threatening (Grade 4) or recurrent Grade 3 colitis upon
re-initiation of BAVENCIO. Immune-mediated colitis occurred in 1.5%
(26/1738) of patients, including seven (0.4%) with Grade 3.

BAVENCIO can cause immune-mediated endocrinopathies, including
adrenal insufficiency, thyroid disorders, and type 1 diabetes
mellitus.

Monitor patients for signs and symptoms of adrenal insufficiency
during and after treatment and administer corticosteroids as
appropriate. Withhold BAVENCIO for severe (Grade 3) or
life-threatening (Grade 4) adrenal insufficiency. Adrenal
insufficiency was reported in 0.5% (8/1738) of patients, including
one (0.1%) with Grade 3.

Thyroid disorders can occur at any time during treatment. Monitor
patients for changes in thyroid function at the start of treatment,
periodically during treatment, and as indicated based on clinical
evaluation. Manage hypothyroidism with hormone replacement therapy
and hyperthyroidism with medical management. Withhold BAVENCIO for
severe (Grade 3) or life threatening (Grade 4) thyroid disorders.
Thyroid disorders including hypothyroidism, hyperthyroidism, and
thyroiditis were reported in 6% (98/1738) of patients, including
three (0.2%) with Grade 3.

Type 1 diabetes mellitus, including diabetic ketoacidosis: Monitor
patients for hyperglycemia or other signs and symptoms of diabetes.
Withhold BAVENCIO and administer antihyperglycemics or insulin in
patients with severe or life-threatening (Grade 3 or greater)
hyperglycemia and resume treatment when metabolic control is
achieved. Type 1 diabetes mellitus without an alternative etiology
occurred in 0.1% (2/1738) of patients, including two cases of Grade 3
hyperglycemia.

BAVENCIO can cause immune-mediated nephritis and renal
dysfunction. Monitor patients for elevated serum creatinine prior to
and periodically during treatment. Administer corticosteroids for
Grade 2 or greater nephritis. Withhold BAVENCIO for moderate (Grade
2) or severe (Grade 3) nephritis until resolution to Grade 1 or
lower. Permanently discontinue BAVENCIO for life-threatening (Grade
4) nephritis. Immune-mediated nephritis occurred in 0.1% (1/1738) of
patients.

BAVENCIO can result in other severe and fatal immune-mediated
adverse reactions involving any organ system during treatment or
after treatment discontinuation. For suspected immune-mediated
adverse reactions evaluate to confirm or rule out an immune-mediated
adverse reaction and to exclude other causes. Depending on the
severity of the adverse reaction, withhold or permanently discontinue
BAVENCIO, administer high dose corticosteroids, and initiate hormone
replacement therapy if appropriate. Resume BAVENCIO when the
immune-mediated adverse reaction remains at Grade 1 or lower
following a corticosteroid taper. Permanently discontinue BAVENCIO
for any severe (Grade 3) immune-mediated adverse reaction that recurs
and for any life-threatening (Grade 4) immune-mediated adverse
reaction. The following clinically significant immune-mediated
adverse reactions occurred in less than 1% of 1738 patients treated
with BAVENCIO: myocarditis with fatal cases, myositis, psoriasis,
arthritis, exfoliative dermatitis, erythema multiforme, pemphigoid,
hypopituitarism, uveitis, Guillain-Barré syndrome, and systemic
inflammatory response.

BAVENCIO can cause severe (Grade 3) or life-threatening (Grade 4)
infusion-related reactions. Patients should be premedicated with an
antihistamine and acetaminophen prior to the first 4 infusions and
for subsequent doses based upon clinical judgment and
presence/severity of prior infusion reactions. Monitor patients for
signs and symptoms of infusion-related reactions, including pyrexia,
chills, flushing, hypotension, dyspnea, wheezing, back pain,
abdominal pain, and urticaria. Interrupt or slow the rate of infusion
for mild (Grade 1) or moderate (Grade 2) infusion-related reactions.
Permanently discontinue BAVENCIO for severe (Grade 3) or
life-threatening (Grade 4) infusion-related reactions.
Infusion-related reactions occurred in 25% (439/1738) of patients,
including three (0.2%) patients with Grade 4 and nine (0.5%) with
Grade 3.

BAVENCIO can cause fetal harm when administered to a pregnant
woman. Advise patients of the potential risk to a fetus including the
risk of fetal death. Advise females of childbearing potential to use
effective contraception during treatment with BAVENCIO and for at
least one month after the last dose of BAVENCIO. It is not known
whether BAVENCIO is excreted in human milk. Advise a lactating woman
not to breastfeed during treatment and for at least one month after
the last dose of BAVENCIO due to the potential for serious adverse
reactions in breastfed infants.

The most common adverse reactions (all grades, greater than or
equal to 20%) in patients with metastatic MCC were fatigue (50%),
musculoskeletal pain (32%), diarrhea (23%), nausea (22%),
infusion-related reactions (22%), rash (22%), decreased appetite
(20%), and peripheral edema (20%). The most common adverse reaction
requiring dose interruption was anemia.

Selected treatment-emergent laboratory abnormalities (all grades,
greater than or equal to 20%) in patients with metastatic MCC were
lymphopenia (49%), anemia (35%), increased aspartate aminotransferase
(34%), thrombocytopenia (27%). and increased alanine aminotransferase
(20%). Selected treatment-emergent Grade 3-4 laboratory abnormalities
(greater than or equal to 2%) were lymphopenia (19%), anemia (9%),
hyperglycemia (7%), increased alanine aminotransferase (5%), and
increased lipase (4%).

INDICATION

BAVENCIO is indicated for the treatment of adults and pediatric
patients 12 years and older with metastatic Merkel cell carcinoma
(MCC). This indication is approved under accelerated approval based
on tumor response and duration of response. Continued approval for
this indication may be contingent upon verification and description
of clinical benefit in confirmatory trials.

About BAVENCIO® (avelumab)

BAVENCIO is a human programmed death ligand-1 (PD-L1) blocking
antibody indicated in the US for the treatment of adults and
pediatric patients 12 years of age and older with metastatic Merkel
cell carcinoma. [1] This indication is approved under accelerated
approval based on tumor response and duration of response. Continued
approval for this indication may be contingent upon verification and
description of clinical benefit in confirmatory trials.

BAVENCIO is not approved in any market outside the US.

About Merck-Pfizer Alliance

Immuno-oncology is a top priority for Merck and Pfizer Inc. The
global strategic alliance between Merck and Pfizer enables the
companies to benefit from each other's strengths and capabilities and
further explore the therapeutic potential of avelumab, an anti-PD-L1
antibody initially discovered and developed by Merck. The
immuno-oncology alliance will jointly develop and commercialize
avelumab and advance Pfizer's PD-1 antibody. The alliance is focused
on developing high-priority international clinical programs to
investigate avelumab as a monotherapy, as well as in combination
regimens, and is striving to find new ways to treat cancer.

About EMD Serono, Inc.

EMD Serono is the biopharmaceutical business of Merck - a leading
science and technology company - in the US and Canada, focused
exclusively on specialty care. For more than 40 years, the business
has integrated cutting-edge science, innovative products and
industry-leading patient support and access programs. EMD Serono has
deep expertise in neurology, fertility and endocrinology, as well as
a robust pipeline of potential therapies in oncology, immuno-oncology
and immunology as R&D focus areas. Today, the business has 1,200
employees around the country with commercial, clinical and research
operations based in the company's home state of Massachusetts.

https://www.emdserono.com

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About Merck

Merck is a leading science and technology company in healthcare,
life science and performance materials. Around 50,000 employees work
to further develop technologies that improve and enhance life - from
biopharmaceutical therapies to treat cancer or multiple sclerosis,
cutting-edge systems for scientific research and production, to
liquid crystals for smartphones and LCD televisions. In 2016, Merck
generated sales of EUR 15.0 billion in 66 countries.

Founded in 1668, Merck is the world's oldest pharmaceutical and
chemical company. The founding family remains the majority owner of
the publicly listed corporate group. Merck, Darmstadt, Germany holds
the global rights to the "Merck" name and brand except in the United
States and Canada, where the company operates as EMD Serono,
MilliporeSigma and EMD Performance Materials.

About Pfizer Inc.: Working together for a healthier world®

At Pfizer, we apply science and our global resources to bring
therapies to people that extend and significantly improve their
lives. We strive to set the standard for quality, safety and value in
the discovery, development and manufacture of health care products.
Our global portfolio includes medicines and vaccines as well as many
of the world's best-known consumer health care products. Every day,
Pfizer colleagues work across developed and emerging markets to
advance wellness, prevention, treatments and cures that challenge the
most feared diseases of our time. Consistent with our responsibility
as one of the world's premier innovative biopharmaceutical companies,
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Pfizer Disclosure Notice

The information contained in this release is as of March 23, 2017.
Pfizer assumes no obligation to update forward-looking statements
contained in this release as the result of new information or future
events or developments.

This release contains forward-looking information about BAVENCIO
(avelumab), including an indication in the US for BAVENCIO for the
treatment of metastatic Merkel cell carcinoma (the Indication),
Pfizer's and Merck's immuno-oncology alliance involving anti-PD-L1
and anti-PD-1 therapies, and clinical development plans, including
their potential benefits, that involves substantial risks and
uncertainties that could cause actual results to differ materially
from those expressed or implied by such statements. Risks and
uncertainties include, among other things, uncertainties regarding
the commercial success of BAVENCIO; the uncertainties inherent in
research and development, including the ability to meet anticipated
clinical study commencement and completion dates and regulatory
submission dates, as well as the possibility of unfavorable study
results, including unfavorable new clinical data and additional
analyses of existing clinical data; risks associated with interim
data; the risk that clinical trial data are subject to differing
interpretations, and, even when we view data as sufficient to support
the safety and/or effectiveness of a product candidate, regulatory
authorities may not share our views and may require additional data
or may deny approval altogether; whether and when drug applications
may be filed in any other jurisdictions for the Indication or in any
jurisdictions for any other potential indications for BAVENCIO,
combination therapies or other product candidates; whether and when
any such applications (including the pending application for the
Indication in the EU) may be approved by regulatory authorities,
which will depend on the assessment by such regulatory authorities of
the benefit-risk profile suggested by the totality of the efficacy
and safety information submitted; decisions by regulatory authorities
regarding labeling and other matters that could affect the
availability or commercial potential of BAVENCIO, combination
therapies or other product candidates; and competitive developments.

A further description of risks and uncertainties can be found in
Pfizer's Annual Report on Form 10-K for the fiscal year ended
December 31, 2016, and in its subsequent reports on Form 10-Q,
including in the sections thereof captioned "Risk Factors" and
"Forward-Looking Information and Factors That May Affect Future
Results", as well as in its subsequent reports on Form 8-K, all of
which are filed with the U.S. Securities and Exchange Commission and
available at http://www.sec.gov and http://www.pfizer.com.

References

1. BAVENCIO Prescribing Information. Rockland, MA: EMD Serono Inc.;
2017.
2. National Institutes of Health, U.S. National Library of Medicine,
Daily Med. Available at
https://dailymed.nlm.nih.gov/dailymed/advanced-search.cfm.
Accessed March 22, 2017.
3. Lemos B, Storer B, Iyer J, et al. Pathologic Nodal Evaluation
Improves Prognostic Accuracy in Merkel Cell Carcinoma: Analysis of
5,823 Cases as the Basis of the First Consensus Staging System for
this Cancer. Journal of the American Academy of Dermatology.
2010;63(5):751-761.

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ots Originaltext: Merck and Pfizer
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Media (EU)
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Ryan Crowe
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