FDA Accepts Supplemental New Drug Application for Pfizer’s IBRANCE® (palbociclib) in HR+, HER2- Metastatic Breast Cancer

NEW YORK–(BUSINESS WIRE)– Pfizer Inc. (NYSE:PFE) today announced that the U.S. Food and Drug
Administration (FDA) has accepted for review a supplemental New Drug
Application (sNDA) for its first-in-class CDK 4/6 inhibitor, IBRANCE^®
(palbociclib). The sNDA supports the conversion of the accelerated
approval of IBRANCE in combination with letrozole to regular approval
and includes data from the Phase 3 PALOMA-2 trial, which evaluated
IBRANCE as initial therapy in combination with letrozole for
postmenopausal women with estrogen receptor-positive, human epidermal
growth factor receptor 2-negative (ER+, HER2-) metastatic breast cancer.
This is the same patient population as the randomized Phase 2 PALOMA-1
trial upon which the accelerated approval of IBRANCE plus letrozole was
granted in February 2015.

The sNDA was granted Priority Review status, which accelerates FDA
review time from 10 months to a goal of six months from the day of
acceptance of filing.¹ The Prescription Drug User Fee Act
(PDUFA) goal date for a decision by the FDA is in April 2017.

“Since its introduction in 2015, more than 45,000 patients have been
prescribed IBRANCE by more than 9,000 providers in the U.S.,” said Liz
Barrett, global president and general manager, Pfizer Oncology. “We are
pleased that the PALOMA-2 trial has further demonstrated the significant
clinical benefit of IBRANCE in the first-line setting, providing
additional evidence for its continued use as a standard of care
medicine.”

PALOMA-2 is a randomized (2:1), multicenter, double-blind Phase 3 study
that evaluated a total of 666 women from 186 global sites in 17
countries. The results of PALOMA-2 were presented at the 52nd American
Society of Clinical Oncology (ASCO) Annual Meeting in June and recently
published in the November 17, 2016 issue of The New England Journal
of Medicine. The study demonstrated that IBRANCE in combination with
letrozole improved progression-free survival compared to letrozole plus
placebo as a first-line treatment for postmenopausal women with ER+,
HER2- metastatic breast cancer. The adverse events observed with IBRANCE
in combination with letrozole in PALOMA-2 were generally consistent with
their respective known adverse event profiles.

About IBRANCE® (palbociclib) 125 mg capsules

IBRANCE is the first and only FDA approved oral inhibitor of CDKs 4 and
6,² which are key regulators of the cell cycle that trigger
cellular progression.^3,4 IBRANCE is approved in more than 50
countries.

In the U.S., IBRANCE is indicated for the treatment of HR+, HER2-
advanced or metastatic breast cancer in combination with letrozole as
initial endocrine based therapy in postmenopausal women, or fulvestrant
in women with disease progression following endocrine therapy.²
The indication in combination with letrozole is approved under
accelerated approval based on PFS. Continued approval for this
indication may be contingent upon verification and description of
clinical benefit in a confirmatory trial.

The full prescribing information for IBRANCE can be found at www.pfizer.com.

IMPORTANT IBRANCE^® (palbociclib) SAFETY
INFORMATION FROM THE U.S. PRESCRIBING INFORMATION

Neutropenia was the most frequently reported adverse reaction in
PALOMA-1 (75%) and PALOMA-3 (83%). In PALOMA-1, Grade 3 (57%) or 4 (5%)
decreased neutrophil counts were reported in patients receiving IBRANCE
plus letrozole. In PALOMA-3, Grade 3 (56%) or Grade 4 (11%) decreased
neutrophil counts were reported in patients receiving IBRANCE plus
fulvestrant. Febrile neutropenia has been reported in about 1% of
patients exposed to IBRANCE. One death due to neutropenic sepsis was
observed in PALOMA-3. Inform patients to promptly report any fever.

Monitor complete blood count prior to starting IBRANCE, at the beginning
of each cycle, on Day 14 of first 2 cycles, and as clinically indicated.
Dose interruption, dose reduction, or delay in starting treatment cycles
is recommended for patients who develop Grade 3 or 4 neutropenia.

Pulmonary embolism (PE) has been reported at a higher rate in
patients treated with IBRANCE plus letrozole in PALOMA-1 (5%) and in
patients treated with IBRANCE plus fulvestrant in PALOMA-3 (1%) compared
with no cases in patients treated either with letrozole alone or
fulvestrant plus placebo. Monitor for signs and symptoms of PE and treat
as medically appropriate.

Based on the mechanism of action, IBRANCE can cause fetal harm.
Advise females of reproductive potential to use effective contraception
during IBRANCE treatment and for at least 3 weeks after the last dose.
IBRANCE may impair fertility in males and has the potential to
cause genotoxicity. Advise male patients with female partners of
reproductive potential to use effective contraception during IBRANCE
treatment and for 3 months after the last dose. Advise females to inform
their healthcare provider of a known or suspected pregnancy. Advise
women not to breastfeed during IBRANCE treatment and for 3 weeks
after the last dose because of the potential for serious adverse
reactions in nursing infants.

The most common adverse reactions (≥10%) of any grade
reported in PALOMA-1 of IBRANCE plus letrozole vs letrozole alone
included neutropenia (75% vs 5%), leukopenia (43% vs 3%), fatigue (41%
vs 23%), anemia (35% vs 7%), upper respiratory infection (31% vs 18%),
nausea (25% vs 13%), stomatitis (25% vs 7%), alopecia (22% vs 3%),
diarrhea (21% vs 10%), thrombocytopenia (17% vs 1%), decreased appetite
(16% vs 7%), vomiting (15% vs 4%), asthenia (13% vs 4%), peripheral
neuropathy (13% vs 5%), and epistaxis (11% vs 1%).

Grade 3/4 adverse reactions (≥10%) in PALOMA-1 reported at
a higher incidence in the IBRANCE plus letrozole group vs the letrozole
alone group included neutropenia (54% vs 1%) and leukopenia (19% vs 0%).
The most frequently reported serious adverse events in patients
receiving IBRANCE plus letrozole were pulmonary embolism (4%) and
diarrhea (2%).

Lab abnormalities occurring in PALOMA-1 (all grades,
IBRANCE plus letrozole vs letrozole alone) were decreased WBC (95% vs
26%), decreased neutrophils (94% vs 17%), decreased lymphocytes (81% vs
35%), decreased hemoglobin (83% vs 40%), and decreased platelets (61% vs
16%).

The most common adverse reactions (≥10%) of any grade reported in PALOMA-3
of IBRANCE plus fulvestrant vs fulvestrant plus placebo included
neutropenia (83% vs 4%), leukopenia (53% vs 5%), infections (47% vs
31%), fatigue (41% vs 29%), nausea (34% vs 28%), anemia (30% vs 13%),
stomatitis (28% vs 13%), headache (26% vs 20%), diarrhea (24% vs 19%),
thrombocytopenia (23% vs 0%), constipation (20% vs 16%), vomiting (19%
vs 15%), alopecia (18% vs 6%), rash (17% vs 6%), decreased appetite (16%
vs 8%), and pyrexia (13% vs 5%).

Grade 3/4 adverse reactions (≥10%) in PALOMA-3 reported at
a higher incidence in the IBRANCE plus fulvestrant group vs the
fulvestrant plus placebo group included neutropenia (66% vs 1%) and
leukopenia (31% vs 2%). The most frequently reported serious adverse
reactions in patients receiving IBRANCE plus fulvestrant were infections
(3%), pyrexia (1%), neutropenia (1%), and pulmonary embolism (1%).

Lab abnormalities occurring in PALOMA-3 (all grades,
IBRANCE plus fulvestrant vs fulvestrant plus placebo) were decreased WBC
(99% vs 26%), decreased neutrophils (96% vs 14%), anemia (78% vs 40%),
and decreased platelets (62% vs 10%).

Avoid concurrent use of strong CYP3A inhibitors. If patients must
be administered a strong CYP3A inhibitor, reduce the IBRANCE dose to 75
mg/day. If the strong inhibitor is discontinued, increase the IBRANCE
dose (after 3-5 half-lives of the inhibitor) to the dose used prior to
the initiation of the strong CYP3A inhibitor. Grapefruit or grapefruit
juice may increase plasma concentrations of IBRANCE and should be
avoided. Avoid concomitant use of strong CYP3A inducers. The dose
of sensitive CYP3A substrates with a narrow therapeutic index may
need to be reduced as IBRANCE may increase their exposure.

IBRANCE has not been studied in patients with moderate to
severe hepatic impairment or in patients with severe renal
impairment (CrCl <30 mL/min).

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.

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, 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
investors on our website at www.pfizer.com.
In addition, to learn more, please visit us on www.pfizer.com
and follow us on Twitter at @Pfizer
and @PfizerNews,
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and like us on Facebook at Facebook.com/Pfizer.

DISCLOSURE NOTICE: The information contained in this release is as of
December 21, 2016. 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 IBRANCE
(palbociclib), including its 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 IBRANCE; the uncertainties inherent
in research and development, including further investigation of the
clinical benefit of IBRANCE, the ability to meet anticipated clinical
trial commencement and completion dates and 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 regulatory authorities will be satisfied
with the design of and results from our clinical studies; whether and
when the sNDA will be approved and whether and when the accelerated
approval for IBRANCE will be converted to regular approval in the U.S.;
whether and when drug applications may be filed in any additional
jurisdictions for IBRANCE for potential HR+/HER2- metastatic breast
cancer indications or in any jurisdictions for any other potential
indications for IBRANCE; whether and when any such other applications
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 IBRANCE; 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, 2015 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 U.S. Food and Drug Administration. Priority Review. http://www.fda.gov/forpatients/approvals/fast/ucm405405.htm.
Accessed November 11, 2016..

² IBRANCE® (palbociclib) Prescribing Information. New York.
NY: Pfizer Inc: 2016.

³ Weinberg RA. pRb and Control of the Cell Cycle Clock. In:
Weinberg RA, ed. The Biology of Cancer. 2nd ed. New York, NY: Garland
Science; 2014:275-329.

⁴ Sotillo E, Grana X. Escape from Cellular Quiescence. In:
Enders GH, ed. Cell Cycle Deregulation in Cancer. New York, NY: Humana
Press; 2010:3-22.

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