FDA Grants BAVENCIO® (avelumab) Approval for a Common Type of Advanced Bladder Cancer

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

- Second approval for BAVENCIO in less than two months
- Advanced urothelial carcinoma is an aggressive disease with a high
rate of recurrence

Merck and Pfizer Inc. (NYSE: PFE) today announced that the US Food
and Drug Administration (FDA) has approved BAVENCIO® (avelumab)
Injection for the treatment of patients with locally advanced or
metastatic urothelial carcinoma (UC) who have disease progression
during or following platinum-containing chemotherapy therapy, or who
have disease progression within 12 months of neoadjuvant or adjuvant
treatment with platinum-containing chemotherapy. BAVENCIO was
previously granted accelerated approval from the FDA for the
treatment of adults and pediatric patients 12 years and older with
metastatic Merkel cell carcinoma (MCC). These indications are
approved under accelerated approval based on tumor response and
duration of response. Continued approval for these indications 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.

"This approval for BAVENCIO in patients with locally advanced or
metastatic urothelial carcinoma exemplifies our unwavering commitment
to finding new treatments for the most challenging cancers," said
Luciano Rossetti, M.D., Executive Vice President, Global Head of
Research & Development at biopharma business of Merck. "Coming just a
few weeks after the approval for metastatic Merkel cell carcinoma, we
continue to demonstrate our ability to accelerate access to
innovative medicines for patients in need."

"This approval builds on the ongoing clinical development program
for BAVENCIO in urothelial carcinoma and reinforces our commitment to
providing new medicines to patients with difficult-to-treat cancers,"
said Liz Barrett, Global President, Pfizer Oncology. "By drawing on
the strength of the alliance, as well as Pfizer's deep experience in
genitourinary cancers, we believe BAVENCIO will be an important
treatment option, and we hope it will help to improve outcomes for
these patients."

Bladder cancer makes up approximately 90% of urothelial carcinomas
and is the sixth most common cancer in the US.[2],[3] When the
disease has metastasized, the five-year survival rate is
approximately 5%.[4] Despite advances in the treatment of locally
advanced or metastatic urothelial carcinoma, the prognosis for
patients remains poor and more treatment options are needed.[2]

"Once urothelial carcinoma progresses after treatment with
chemotherapy, the five-year survival rate is alarmingly low," said
Dr. Andrea Apolo, National Cancer Institute, Bethesda, MD. "Until
recently, there had been limited innovation in urothelial carcinoma,
and this approval gives us another treatment to help battle this
aggressive disease."

The efficacy and safety of BAVENCIO was demonstrated in the
urothelial carcinoma cohorts (N=242) of the JAVELIN Solid Tumor
trial, a Phase I, open-label, single-arm, multicenter study of
BAVENCIO in the treatment of various solid tumors. The urothelial
carcinoma cohorts enrolled patients with locally advanced or
metastatic urothelial carcinoma with disease progression on or after
platinum-containing chemotherapy or who had disease progression
within 12 months of treatment with a platinum-containing neoadjuvant
or adjuvant chemotherapy regimen. These data will be presented at an
upcoming medical congress.

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)
in patients with locally advanced or metastatic urothelial carcinoma
were fatigue (41%), infusion-related reaction (30%), musculoskeletal
pain (25%), nausea (24%), decreased appetite/hypophagia (21%) and
urinary tract infection (21%).[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 also been shown to induce
antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.[1]

The alliance is committed to providing industry-leading patient
access and reimbursement support through its CoverOne(TM) program in
the United States. 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 Urothelial Carcinoma Cohorts in JAVELIN Solid Tumor Trial

The efficacy and safety of BAVENCIO was demonstrated in the
urothelial carcinoma cohorts of the JAVELIN Solid Tumor trial, a
Phase I, open-label, single-arm, multicenter study that included 242
patients with locally advanced or metastatic urothelial carcinoma
with disease progression on or after platinum-containing chemotherapy
or who had disease progression within 12 months of treatment with a
platinum-containing neoadjuvant or adjuvant chemotherapy regimen who
were treated with BAVENCIO.

Patients with active or a history of central nervous system
metastasis; other malignancies within the last five years; an organ
transplant; conditions requiring therapeutic immune suppression; or
active infection with HIV, hepatitis B or C were excluded. Patients
with autoimmune disease, other than type 1 diabetes, vitiligo,
psoriasis, or thyroid disease that did not require immunosuppressive
treatment, were excluded. Patients were included regardless of their
PD-L1 status. Patients received BAVENCIO at a dose of 10 mg/kg
intravenously over 60 minutes every two weeks until disease
progression or unacceptable toxicity. Tumor response assessments were
performed every six weeks, as assessed by an Independent Endpoint
Review Committee (IERC) using Response Evaluation Criteria in Solid
Tumors (RECIST) v1.1. Efficacy outcome measures included confirmed
overall response rate (ORR) and duration of response (DOR). Efficacy
measures were evaluated in patients who were followed for a minimum
of both 13 weeks and 6 months at the time of data cut-off.

Out of the total 226 patients evaluable for efficacy, 44% had
non-bladder urothelial carcinoma, including 23% of patients with
upper tract disease; 83% of patients had visceral metastases; 34% of
patients had liver metastases. Nine patients (4%) had disease
progression following prior platinum-containing neoadjuvant or
adjuvant therapy only. Forty-seven percent of patients only received
prior cisplatin-based regimens, 32% received only prior
carboplatin-based regimens, and 20% received both cisplatin and
carboplatin-based regimens.

The international clinical development program for avelumab, known
as JAVELIN, involves more than 30 clinical programs, including nine
Phase III trials, and more than 5,200 patients across more than 15
tumor types.

In December 2015, Merck and Pfizer announced the initiation of a
Phase III multicenter, multinational, randomized, open-label,
parallel-arm study (JAVELIN Bladder 100) of BAVENCIO plus best
supportive care versus best supportive care alone as a maintenance
treatment in patients with locally advanced or metastatic urothelial
carcinoma whose disease did not progress after completion of
first-line platinum-containing chemotherapy. This trial is currently
enrolling patients.

IMPORTANT SAFETY INFORMATION and INDICATIONS

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 anti-hyperglycemics or insulin in
patients with severe or life-threatening (Grade >= 3) 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 1 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 1 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, >= 20%) in patients
with metastatic Merkel cell carcinoma (MCC) were fatigue (50%),
musculoskeletal pain (32%), diarrhea (23%), nausea (22%),
infusion-related reaction (22%), rash (22%), decreased appetite
(20%), and peripheral edema (20%).

Selected treatment-emergent laboratory abnormalities (all grades,
>= 20%) in patients with metastatic MCC were lymphopenia (49%),
anemia (35%), increased aspartate aminotransferase (34%),
thrombocytopenia (27%), and increased alanine aminotransferase (20%).

The most common adverse reactions (all grades, >= 20%) in patients
with locally advanced or metastatic urothelial cancer (UC) were
fatigue (41%), infusion-related reaction (30%), musculoskeletal pain
(25%), nausea (24%), decreased appetite/hypophagia (21%) and urinary
tract infection (21%).

Selected laboratory abnormalities (grades 3-4, >= 3%) in patients
with locally advanced or metastatic UC were hyponatremia (16%),
gamma-glutamyltransferase increased (12%), lymphopenia (11%),
hyperglycemia (9%), increased alkaline phosphatase (7%), anemia (6%),
increased lipase (6%), hyperkalemia (3%), and increased aspartate
aminotransferase (3%).

INDICATIONS

BAVENCIO is indicated for the treatment of adults and pediatric
patients 12 years and older with metastatic Merkel cell carcinoma
(MCC).

BAVENCIO is indicated for the treatment of patients with locally
advanced or metastatic urothelial carcinoma (UC) who have disease
progression during or following platinum-containing chemotherapy or
have disease progression within 12 months of neoadjuvant or adjuvant
treatment with platinum-containing chemotherapy.

These indications are approved under accelerated approval based on
tumor response and duration of response. Continued approval for these
indications may be contingent upon verification and description of
clinical benefit in confirmatory trials.

Avelumab has not yet been approved for any indication in any
market outside of the US. As announced on October 31, 2016, the
European Medicines Agency (EMA) has validated for review Merck's
Marketing Authorization Application for avelumab, for the proposed
indication of metastatic Merkel cell carcinoma.

About BAVENCIO® (avelumab)

BAVENCIO is a human programmed death ligand-1 (PD-L1) blocking
antibody indicated in the US for the treatment of patients with
locally advanced or metastatic urothelial carcinoma who have disease
progression during or following platinum-containing chemotherapy or
who have disease progression within 12 months of neoadjuvant or
adjuvant treatment with platinum-containing chemotherapy, as well as
for the treatment of adults and pediatric patients 12 years and older
with metastatic Merkel cell carcinoma.[1] These indications are
approved under accelerated approval based on tumor response and
duration of response. Continued approval for these indications is
contingent upon verification and description of clinical benefit in
confirmatory trials.

BAVENCIO is not approved for any indication 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.

http://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
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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
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Pfizer Disclosure Notice

The information contained in this release is as of May 9, 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), Merck-Pfizer's 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 BAVENCIO for metastatic Merkel
cell carcinoma 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 Cancer Institute. Bladder Cancer Treatment (PDQ) - Health
Professional Version. Available at
https://www.cancer.gov/types/bladder/hp/bladder-treatment-pdq.
Accessed May 9, 2017.
3. National Comprehensive Cancer Network. NCCN Guidelines Version
1.2017 Updates. Bladder Cancer. Available from:
https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf.
Accessed May 9, 2017.
4. National Cancer Institute. The Surveillance, Epidemiology, and End
Results (SEER): Cancer Stat Facts: Bladder Cancer. Available at:
https://seer.cancer.gov/statfacts/html/urinb.html. Accessed May 9,
2017.

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Investor Relations: Ryan Crowe
+1-212-733-8160.

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