Pfizer Announces Outcome of FDA Advisory Committee Meeting for SUTENT® in Patients at High Risk of Recurrent Renal Cell Carcinoma after Surgery

NEW YORK–(BUSINESS WIRE)– Pfizer Inc. (NYSE:PFE) today announced that the U.S. Food and Drug
Administration’s (FDA) Oncologic Drug Advisory Committee (ODAC) voted 6
in favor and 6 against the benefit-risk profile for SUTENT^®
(sunitinib) as adjuvant treatment of adult patients at high risk of
recurrent renal cell carcinoma (RCC) after nephrectomy (surgical removal
of the cancer-containing kidney). The role of the Advisory Committee is
to provide recommendations to the FDA. The ODAC discussions were based
on the supplemental New Drug Application (sNDA) currently under review
by the FDA. The FDA decision on whether or not to approve the sNDA is
anticipated by January 2018.

Approximately 75 percent of patients with clear cell RCC are
non-metastatic, and 70-80 percent will have a nephrectomy with curative
intent, or surgical removal of the tumor.¹ High-risk patients
represent approximately 15 percent of all patients with primary resected
RCC and approximately 60 percent of these high-risk patients will have
recurrence and develop metastatic disease within five years.²
The current treatment is surgery followed by observation. This treatment
is suboptimal for patients at high risk of recurrence.

“We are encouraged by today’s productive discussion and look forward to
working with the FDA over the next few weeks as they incorporate today’s
discussion into their review and decision regarding SUTENT in this
patient population,” said Mace Rothenberg, MD, Chief Development
Officer, Oncology, Pfizer Global Product Development. “SUTENT has long
been a standard of care for the treatment of advanced RCC and we believe
that this potential benefit can be extended into patients with high-risk
of RCC recurrence, as demonstrated in the S-TRAC trial.”

The sNDA under review by the FDA is based on results from the S-TRAC
trial, a randomized double-blind Phase 3 trial of adjuvant SUTENT vs.
placebo in 615 patients with locoregional, resected RCC at high risk of
recurrence. The study met its primary endpoint of improving disease-free
survival (DFS), and the results were published by The New
England Journal of Medicine in October 2016.

SUTENT was first approved in the United States in 2006 for the treatment
of advanced RCC, where it is the most widely prescribed first-line
treatment. Now approved in 119 countries,³ more than 350,000
patients have been treated with SUTENT in its approved indications of
advanced RCC, imatinib-resistant or -intolerant gastrointestinal stromal
tumors (GIST) and advanced pancreatic neuroendocrine tumors (pNET).⁴
Use of SUTENT is not approved in the adjuvant setting. SUTENT is
supported by an extensive body of evidence in scientific literature,
including more than 440 publications.

The ODAC is an independent panel of experts that evaluates data
concerning the efficacy and safety of marketed and investigational
cancer treatments and makes recommendations to the FDA. Its vote is not
binding, but is considered by the FDA in its decision making process.

As a leader in the treatment of advanced RCC, Pfizer is dedicated to
meeting the unmet needs of these patients and advancing the science of
RCC through research into established and novel compounds. Our near term
areas of focus include expanding access of our marketed products,
exploration of biomarkers to better personalize therapy and
immunotherapy combinations.

About SUTENT^® (sunitinib malate)

SUTENT is an oral multi-kinase inhibitor that works by blocking multiple
molecular targets implicated in the growth, proliferation and spread of
cancer. Two important SUTENT targets, vascular endothelial growth factor
receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) are
expressed by many types of solid tumors and are thought to play a
crucial role in angiogenesis, the process by which tumors acquire blood
vessels, oxygen and nutrients needed for growth. SUTENT also inhibits
other targets important to tumor growth, including KIT, FLT3 and RET.

SUTENT Important Safety Information

Boxed Warning/Hepatotoxicity: Hepatotoxicity has been observed in
clinical trials and post-marketing experience. This hepatotoxicity
may be severe, and deaths have been reported. Monitor liver function
tests before initiation of treatment, during each cycle of treatment,
and as clinically indicated. SUTENT should be interrupted for Grade 3 or
4 drug-related hepatic adverse events and discontinued if there is no
resolution. Do not restart SUTENT if patients subsequently experience
severe changes in liver function tests or have other signs and symptoms
of liver failure.

Pregnancy: Women of childbearing potential should be advised of
the potential hazard to the fetus and to avoid becoming pregnant.

Nursing mothers: Given the potential for serious adverse
reactions (ARs) in nursing infants, a decision should be made whether to
discontinue nursing or SUTENT.

Cardiovascular events: Cardiovascular events, including heart
failure, cardiomyopathy, myocardial ischemia, and myocardial infarction,
some of which were fatal, have been reported. Use SUTENT with caution in
patients who are at risk for, or who have a history of, these events.
Monitor patients for signs and symptoms of congestive heart failure
(CHF) and, in the presence of clinical manifestations, discontinuation
is recommended. Patients who presented with cardiac events, pulmonary
embolism, or cerebrovascular events within the previous 12 months were
excluded from clinical studies.

QT interval prolongation and Torsades de Pointes: SUTENT has been
shown to prolong QT interval in a dose-dependent manner, which may lead
to an increased risk for ventricular arrhythmias including Torsades de
Pointes, which has been seen in <0.1% of patients. Monitoring with
on-treatment electrocardiograms and electrolytes should be considered.

Hypertension: Hypertension may occur. Monitor blood pressure and
treat as needed with standard antihypertensive therapy. In cases of
severe hypertension, temporary suspension of SUTENT is recommended until
hypertension is controlled.

Reversible posterior leukoencephalopathy syndrome (RPLS): There
have been (<1%) reports, some fatal, of subjects presenting with
seizures and radiological evidence of RPLS.

Hemorrhagic events: Hemorrhagic events, including tumor-related
hemorrhage such as pulmonary hemorrhage, have occurred. Some of these
events were fatal. Perform serial complete blood counts (CBCs) and
physical examinations.

Tumor lysis syndrome (TLS): Cases of TLS have been reported
primarily in patients with high tumor burden. Monitor these patients
closely and treat as clinically indicated.

Thrombotic microangiopathy (TMA): TMA, including thrombotic
thrombocytopenic purpura and hemolytic uremic syndrome, sometimes
leading to renal failure or a fatal outcome, has been reported in
patients who received SUTENT as monotherapy and in combination with
bevacizumab. Discontinue SUTENT in patients developing TMA. Reversal of
the effects of TMA has been observed after treatment was discontinued.

Proteinuria: Proteinuria and nephrotic syndrome have been
reported. Some of these cases have resulted in renal failure and fatal
outcomes. Perform baseline and periodic urinalysis during treatment,
with follow-up measurement of 24-hour urine protein as clinically
indicated. Interrupt SUTENT and dose reduce if 24-hour urine protein is
≥3 g; discontinue SUTENT in cases of nephrotic syndrome or repeat
episodes of urine protein ≥3 g despite dose reductions.

Dermatologic toxicities: Severe cutaneous reactions have been
reported, including cases of erythema multiforme (EM), Stevens-Johnson
syndrome (SJS), and toxic epidermal necrolysis (TEN), some of which were
fatal. If signs or symptoms of EM, SJS, or TEN are present, SUTENT
treatment should be discontinued. If a diagnosis of SJS or TEN is
suspected, treatment must not be re-started. Necrotizing fasciitis,
including fatal cases, has been reported, including of the perineum and
secondary to fistula formation. Discontinue SUTENT in patients who
develop necrotizing fasciitis.

Thyroid dysfunction: Thyroid dysfunction may occur. Monitor
thyroid function in patients with signs and/or symptoms of thyroid
dysfunction, including hypothyroidism, hyperthyroidism, and thyroiditis,
and treat per standard medical practice.

Hypoglycemia: SUTENT has been associated with symptomatic
hypoglycemia, which may result in loss of consciousness or require
hospitalization. Reductions in blood glucose levels may be worse in
patients with diabetes. Check blood glucose levels regularly during and
after discontinuation of SUTENT. Assess whether anti-diabetic drug
dosage needs to be adjusted to minimize the risk of hypoglycemia.

Osteonecrosis of the jaw (ONJ): ONJ has been reported. Consider
preventive dentistry prior to treatment with SUTENT. If possible, avoid
invasive dental procedures, particularly in patients receiving
bisphosphonates.

Wound healing: Cases of impaired wound healing have been reported.
Temporary interruption of therapy with SUTENT is recommended in patients
undergoing major surgical procedures.

Adrenal function: Adrenal hemorrhage was observed in animal
studies. Monitor adrenal function in case of stress such as surgery,
trauma, or severe infection.

Laboratory tests: CBCs with platelet count and serum chemistries
including phosphate should be performed at the beginning of each
treatment cycle for patients receiving treatment with SUTENT.

CYP3A4 coadministration: Dose adjustments are recommended when
SUTENT is administered with CYP3A4 inhibitors or inducers. During
treatment with SUTENT, patients should not drink grapefruit juice, eat
grapefruit, or take St John’s Wort.

Most common ARs & most common grade 3/4 ARs (advanced RCC):
The most common ARs occurring in ≥20% of patients receiving SUTENT for
treatment-naïve metastatic RCC (all grades, vs IFNα) were diarrhea (66%
vs 21%), fatigue (62% vs 56%), nausea (58% vs 41%), anorexia (48% vs
42%), altered taste (47% vs 15%), mucositis/stomatitis (47% vs 5%), pain
in extremity/limb discomfort (40% vs 30%), vomiting (39% vs 17%),
bleeding, all sites (37% vs 10%), hypertension (34% vs 4%), dyspepsia
(34% vs 4%), arthralgia (30% vs 19%), abdominal pain (30% vs 12%), rash
(29% vs 11%), hand-foot syndrome (29% vs 1%), back pain (28% vs 14%),
cough (27% vs 14%), asthenia (26% vs 22%), dyspnea (26% vs 20%), skin
discoloration/yellow skin (25% vs 0%), peripheral edema (24% vs 5%),
headache (23% vs 19%), constipation (23% vs 14%), dry skin (23% vs 7%),
fever (22% vs 37%), and hair color changes (20% vs <1%).

The most common grade 3/4 ARs (occurring in ≥5% of patients with RCC
receiving SUTENT vs IFNα) were fatigue (15% vs 15%), hypertension (13%
vs <1%), asthenia (11% vs 6%), diarrhea (10% vs <1%), hand-foot syndrome
(8% vs 0%), dyspnea (6% vs 4%), nausea (6% vs 2%), back pain (5% vs 2%),
pain in extremity/limb discomfort (5% vs 2%), vomiting (5% vs 1%), and
abdominal pain (5% vs 1%).

Most common grade 3/4 lab abnormalities (advanced RCC): The most common
grade 3/4 lab abnormalities (occurring in ≥5% of patients with RCC
receiving SUTENT vs IFNα) included lymphocytes (18% vs 26%), lipase (18%
vs 8%), neutrophils (17% vs 9%), uric acid (14% vs 8%), platelets (9% vs
1%), hemoglobin (8% vs 5%), sodium decreased (8% vs 4%), leukocytes (8%
vs 2%), glucose increased (6% vs 6%), phosphorus (6% vs 6%), and amylase
(6% vs 3%).

Most common ARs & most common grade 3/4 ARs (imatinib-resistant or
-intolerant GIST): The most common ARs occurring in ≥20% of patients
with GIST and more commonly with SUTENT than placebo (all grades, vs
placebo) were diarrhea (40% vs 27%), anorexia (33% vs 29%), skin
discoloration (30% vs 23%), mucositis/stomatitis (29% vs 18%), asthenia
(22% vs 11%), altered taste (21% vs 12%), and constipation (20% vs 14%).
The most common grade 3/4 ARs (occurring in ≥4% of patients with GIST
receiving SUTENT vs placebo) were asthenia (5% vs 3%), hand-foot
syndrome (4% vs 3%), diarrhea (4% vs 0%), and hypertension (4% vs 0%).

Most common grade 3/4 lab abnormalities (imatinib-resistant or
-intolerant GIST): The most common grade 3/4 lab abnormalities
(occurring in ≥5% of patients with GIST receiving SUTENT vs placebo)
included lipase (10% vs 7%), neutrophils (10% vs 0%), amylase (5% vs
3%), and platelets (5% vs 0%).

Most common ARs & most common grade 3/4 ARs (advanced pNET):
The most common ARs occurring in ≥20% of patients with advanced pNET and
more commonly with SUTENT than placebo (all grades, vs placebo) were
diarrhea (59% vs 39%), stomatitis/oral syndromes (48% vs 18%), nausea
(45% vs 29%), abdominal pain (39% vs 34%), vomiting (34% vs 31%),
asthenia (34% vs 27%), fatigue (33% vs 27%), hair color changes (29% vs
1%), hypertension (27% vs 5%), hand-foot syndrome (23% vs 2%), bleeding
events (22% vs 10%), epistaxis (21% vs 5%), and dysgeusia (21% vs 5%).
The most commonly reported grade 3/4 ARs (occurring in ≥5% of patients
with advanced pNET receiving SUTENT vs placebo) were hypertension (10%
vs 1%), hand-foot syndrome (6% vs 0%), stomatitis/oral syndromes (6% vs
0%), abdominal pain (5% vs 10%), fatigue (5% vs 9%), asthenia (5% vs
4%), and diarrhea (5% vs 2%).

Most common grade 3/4 lab abnormalities (advanced pNET): The most
common grade 3/4 lab abnormalities (occurring in ≥5% of patients with
advanced pNET receiving SUTENT vs placebo) included decreased
neutrophils (16% vs 0%), increased glucose (12% vs 18%), increased
alkaline phosphatase (10% vs 11%), decreased phosphorus (7% vs 5%),
decreased lymphocytes (7% vs 4%), increased creatinine (5% vs 5%),
increased lipase (5% vs 4%), increased AST (5% vs 3%), and decreased
platelets (5% vs 0%).

Please see full Prescribing Information, including BOXED WARNING and
Medication Guide, for SUTENT® (sunitinib malate) at www.SUTENT.com.

About Pfizer Oncology

Pfizer Oncology is committed to pursuing innovative treatments that have
a meaningful impact on those living with cancer. As a leader in oncology
speeding cures and accessible breakthrough medicines to patients, Pfizer
Oncology is helping to redefine life with cancer. Our strong pipeline of
biologics, small molecules and immunotherapies, one of the most robust
in the industry, is studied with precise focus on identifying and
translating the best scientific breakthroughs into clinical application
for patients across a wide range of cancers. By working collaboratively
with academic institutions, individual researchers, cooperative research
groups, governments and licensing partners, Pfizer Oncology strives to
cure or control cancer with its breakthrough medicines. Because Pfizer
Oncology knows that success in oncology is not measured solely by the
medicines you manufacture, but rather by the meaningful partnerships you
make to have a more positive impact on people’s lives.

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 healthcare products. Our global portfolio
includes medicines and vaccines as well as many of the world’s
best-known consumer healthcare 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, we collaborate with
health care providers, governments and local communities to support and
expand access to reliable, affordable health care around the world. For
more than 150 years, we have worked to make a difference for all who
rely on us. We routinely post information that may be important to
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addition, to learn more, please visit us on www.Pfizer.com
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and like us on Facebook at Facebook.com/Pfizer.

DISCLOSURE NOTICE: The information contained in this release
is as of September 19, 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 SUTENT and a
potential new indication for SUTENT for the treatment of RCC in the
adjuvant setting (the “potential indication”), 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, the uncertainties inherent in research and development,
including the ability to meet anticipated regulatory submission dates,
as well as the possibility of unfavorable clinical trial results,
including unfavorable new clinical data and additional analyses of
existing clinical data; whether and when any supplemental new drug
applications may be filed in any other jurisdictions for the potential
indication; whether and when the sNDA or any such other applications
that may be pending or filed for the potential indication may be
approved by the FDA or other regulatory authorities, respectively, 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 SUTENT, including for the potential
indication; 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 www.sec.gov
and www.pfizer.com.

¹ Based on comparison between 2015 Swedish population study
(76%), Navigant interviews (95%), and Quant Pulse (79%). 2018-2022.

² Wheler J, Johnson M, Seidman A. Adjuvant therapy with
aromatase inhibitors for postmenopausal women with early breast cancer:
evidence and ongoing controversy. Semin Oncol; 2006; 33(6): 672-80.

³ Pfizer Data on File.

⁴ Based on comparison between 2015 Swedish population study
(76%), Navigant interviews (95%), and Quant Pulse (79%). 2018-2022.

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