VIZIMPRO® (dacomitinib) Receives Marketing Authorization in European Union (EU) for the First-Line Treatment of Adult Patients with EGFR-Mutated Non-Small Cell Lung Cancer

April 4, 2019 Off By BusinessWire

NEW YORK–(BUSINESS WIRE)–Pfizer Inc. (NYSE: PFE) today announced that the European Commission has
approved VIZIMPRO^® (dacomitinib), a tyrosine kinase inhibitor
(TKI), as monotherapy for the first-line treatment of adult patients
with locally advanced or metastatic non-small cell lung cancer (NSCLC)
with epidermal growth factor receptor (EGFR)-activating mutations.

“Lung cancer remains the leading cause of cancer-related death worldwide
and despite advances in biomarker-driven therapies, overcoming
resistance continues to be crucial in treating EGFR-mutated non-small
cell lung cancer,” said Andreas Penk, M.D., regional president, Oncology
International Developed Markets at Pfizer. “The marketing authorization
of VIZIMPRO, which has shown a more than five-month improvement in
progression-free survival over an existing therapy in a Phase 3 clinical
trial, provides a new option for patients with EGFR-mutated non-small
cell lung cancer and reinforces Pfizer’s ongoing commitment to
addressing the remaining needs of the thousands of EU patients with this
disease.”

The European Commission’s approval of VIZIMPRO was supported by data
from ARCHER 1050, a randomized, multicenter, multinational, open-label,
Phase 3 study conducted in patients with unresectable, metastatic or
recurrent NSCLC harboring EGFR exon 19 deletion or exon 21 L858R
substitution mutations. A total of 452 patients were randomized 1:1 to
VIZIMPRO 45 mg (n=227) or gefitinib 250 mg (n=225). The primary endpoint
was progression-free survival (PFS) as determined by blinded Independent
Radiologic Central (IRC) review. Key secondary endpoints included PFS
assessed by the investigator, objective response rate (ORR), duration of
response (DoR) and overall survival (OS).

A statistically significant improvement in PFS as determined by the IRC
was demonstrated for patients randomized to VIZIMPRO compared with
gefitinib (HR = 0.59 [95% CI: 0.47, 0.74], p <0.0001). Median PFS in the
VIZIMPRO group was 14.7 months (95% CI: 11.1, 16.6) compared with 9.2
months (95% CI: 9.1, 11.0) in the gefitinib arm.

“Over the last two decades, biomarker-driven therapies have become
standard-of-care for patients with EGFR-mutated non-small cell lung
cancer,” said Dr. Federico Cappuzzo, Director of Oncology and Hematology
Department AUSL della Romagna-Ravenna. “The improvement in
progression-free survival for VIZIMPRO over a first-generation
standard-of-care therapy in the ARCHER 1050 study is impressive, and I’m
pleased it will be available for appropriate patients with non-small
cell lung cancer in the EU.”

OS results from the final analysis (data cut-off date of 17-Feb-2017)
performed when 48.7 percent of events had occurred, showed a gain of 7.3
months in median OS for patients treated with VIZIMPRO compared to those
treated with gefitinib (34.1 months vs. 26.8 months; HR: 0.760 [95% CI:
0.582, 0.993]). However, the statistical significance of the OS
improvement could not formally be assessed, as the secondary endpoints
from the study were tested in descending order of perceived importance
and stopped when no additional statistical significance of ORR was
reached.

Among 227 patients with EGFR-mutated metastatic NSCLC who received
VIZIMPRO in ARCHER 1050, the most common (≥ 20%) adverse reactions were
diarrhea (87%), rash (77%), stomatitis (70%), nail disorder (66%),
decreased appetite (31%), dry skin (30%), weight decreased (26%),
transaminases increased (24%), conjunctivitis (23%), alopecia (23%), and
pruritus (20%). Serious adverse reactions occurred in 6.2 percent of
patients treated with VIZIMPRO. The most common (≥ 1%) serious adverse
reactions reported were diarrhea (2.2%) and interstitial lung disease
(1.3%).^1,2

About VIZIMPRO^® (dacomitinib), 45 mg, 30 mg
and 15 mg tablets

VIZIMPRO is an oral, once-daily, irreversible pan-human epidermal growth
factor receptor kinase inhibitor. VIZIMPRO is approved in the EU for the
first-line treatment of adult patients with locally advanced or
metastatic non-small cell lung cancer (NSCLC) with epidermal growth
factor receptor (EGFR)-activating mutations.

VIZIMPRO is also approved in the United States for the first-line
treatment of patients with metastatic NSCLC with EGFR exon 19 deletion
or exon 21 L858R substitution mutations as detected by an FDA-approved
test. Additionally, VIZIMPRO is approved in Japan for EGFR gene
mutation-positive, inoperable or recurrent NSCLC, and in Canada for the
first-line treatment of adult patients with unresectable locally
advanced or metastatic NSCLC with confirmed EGFR exon 19 deletion or
exon 21 L858R substitution mutations. The applications in the US and
Japan were reviewed and approved under the Priority Review program.

In 2012, Pfizer and SFJ Pharmaceuticals entered into a collaborative
development agreement to conduct ARCHER 1050 across multiple sites. SFJ
is a global drug development company, which provides a unique and highly
customized co-development partnering model for the world’s top
pharmaceutical and biotechnology companies. Under the terms of this
agreement, SFJ Pharmaceuticals provided the funding and conducted the
trial to generate the clinical data used to support this application.
Pfizer retains all rights to commercialize VIZIMPRO globally.

About ARCHER 1050

The efficacy of VIZIMPRO was demonstrated in ARCHER 1050, a global Phase
3 head-to-head trial conducted in patients with unresectable, metastatic
or recurrent non-small cell lung cancer (NSCLC) harboring epidermal
growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R
substitution mutations, with no prior therapy for metastatic disease or
recurrent disease with a minimum of 12 months disease-free after
completion of systemic therapy. A total of 452 patients were randomized
1:1 to VIZIMPRO 45 mg (n=227) or gefitinib 250 mg (n=225). Randomization
was stratified by region and EGFR mutation status. The primary endpoint
of the study was progression-free survival (PFS) as determined by
blinded Independent Radiology Central (IRC) review. Key secondary
endpoints included PFS assessed by the investigator, objective response
rate (ORR), duration of response (DoR), overall survival (OS), and
patient-reported outcomes (PROs).

VIZIMPRO^® (dacomitinib) IMPORTANT SAFETY
INFORMATION FROM THE U.S. PRESCRIBING INFORMATION

There are no contraindications for VIZIMPRO.

Interstitial Lung Disease (ILD): Severe and fatal ILD/pneumonitis
occurred in patients treated with VIZIMPRO and occurred in 0.5% of the
394 VIZIMPRO-treated patients; 0.3% of cases were fatal. Monitor
patients for pulmonary symptoms indicative of ILD/pneumonitis. Withhold
VIZIMPRO and promptly investigate for ILD in patients who present with
worsening of respiratory symptoms which may be indicative of ILD (e.g.,
dyspnea, cough, and fever). Permanently discontinue VIZIMPRO if ILD is
confirmed.

Diarrhea: Severe and fatal diarrhea occurred in patients treated
with VIZIMPRO. Diarrhea occurred in 86% of the 394 VIZIMPRO-treated
patients. Grade 3 or 4 diarrhea was reported in 11% of patients and 0.3%
of cases were fatal. Withhold VIZIMPRO for Grade 2 or greater diarrhea
until recovery to less than or equal to Grade 1 severity, then resume
VIZIMPRO at the same or a reduced dose depending on the severity of
diarrhea. Promptly initiate anti-diarrheal treatment (loperamide or
diphenoxylate hydrochloride with atropine sulfate) for diarrhea.

Dermatologic Adverse Reactions: Rash and exfoliative skin
reactions occurred in patients treated with VIZIMPRO. Rash occurred in
78% of the 394 VIZIMPRO-treated patients. Grade 3 or 4 rash was reported
in 21% of patients. Exfoliative skin reactions of any severity were
reported in 7% of patients. Grade 3 or 4 exfoliative skin reactions were
reported in 1.8% of patients. Withhold VIZIMPRO for persistent Grade 2
or any Grade 3 or 4 dermatologic adverse reaction until recovery to less
than or equal to Grade 1 severity, then resume VIZIMPRO at the same or a
reduced dose depending on the severity of the dermatologic adverse
reaction. The incidence and severity of rash and exfoliative skin
reactions may increase with sun exposure. At the time of initiation of
VIZIMPRO, initiate use of moisturizers and appropriate measures to limit
sun exposure. Upon development of Grade 1 rash, initiate treatment with
topical antibiotics and topical steroids. Initiate oral antibiotics for
Grade 2 or more severe dermatologic adverse reactions.

Embryo-Fetal Toxicity: VIZIMPRO can cause fetal harm when
administered to a pregnant woman. Advise pregnant women of the potential
risk to the fetus. Advise females of reproductive potential to use
effective contraception during treatment with VIZIMPRO and for at least
17 days after the final dose.

Adverse Reactions: The most common (>20%) adverse reactions were
diarrhea (87%), rash (69%), paronychia (64%), stomatitis (45%),
decreased appetite (31%), dry skin (30%), decreased weight (26%),
alopecia (23%), cough (21%), and pruritus (21%). The most common (≥1%)
serious adverse reactions were diarrhea (2.2%) and interstitial lung
disease (1.3%).

Drug Interactions: Concomitant use with a proton pump inhibitor
(PPI) decreases dacomitinib concentrations, which may reduce VIZIMPRO
efficacy. Avoid the concomitant use of PPIs with VIZIMPRO. As an
alternative to PPIs, use locally-acting antacids or an H2-receptor
antagonist. Administer VIZIMPRO at least 6 hours before or 10 hours
after taking an H2-receptor antagonist. Concomitant use of VIZIMPRO
increases the concentration of drugs that are CYP2D6 substrates which
may increase the risk of toxicities of these drugs. Avoid concomitant
use of VIZIMPRO with CYP2D6 substrates where minimal increases in
concentration of the CYP2D6 substrate may lead to serious or
life-threatening toxicities.

Lactation: Because of the potential for serious adverse reactions
in breastfed infants from VIZIMPRO, advise women not to breastfeed
during treatment with VIZIMPRO and for at least 17 days after the last
dose.

Hepatic Impairment: No dose adjustment is recommended in patients
with mild or moderate hepatic impairment. The recommended dose of
VIZIMPRO has not been established for patients with severe hepatic
impairment.

Renal Impairment: No dose adjustment is recommended for patients
with mild or moderate renal impairment. The recommended dose of VIZIMPRO
has not been established for patients with severe renal impairment.

Please see full prescribing information at Pfizer.com

About Non-Small Cell Lung Cancer

Lung cancer is the most common cancer worldwide, with more than two
million new cases diagnosed globally in 2018.¹ About 85
percent of all lung cancers are identified as non-small cell, and
approximately 75 percent of these are metastatic, or advanced, at
diagnosis.²

EGFR is a protein that helps cells grow and divide. When the EGFR gene
is mutated it can cause the protein to be overactive resulting in cancer
cells to form. EGFR mutations may occur in 10 to 35 percent of NSCLC
tumors globally, and the most common activating mutations are deletions
in exon 19 and exon 21 L858R substitution, which together account for
more than 80 percent of known activating EGFR mutations. The disease is
associated with low survival rates and disease progression remains a
challenge.^3,4

About Pfizer in Lung Cancer

Pfizer Oncology is committed to addressing the unmet needs of patients
with lung cancer, the leading cause of cancer-related deaths worldwide
and a particularly difficult-to-treat disease. Pfizer strives to address
the diverse and evolving needs of patients with non-small cell lung
cancer (NSCLC) by developing efficacious and tolerable therapies,
including biomarker-driven therapies and immuno-oncology (IO) agents and
combinations. By combining leading scientific insights with a
patient-centric approach, Pfizer is continually advancing its work to
match the right patient with the right medicine at the right time.
Through our growing research pipeline and collaboration efforts, we are
committed to delivering renewed hope to patients living with NSCLC.

About Pfizer Oncology

At Pfizer Oncology, we are committed to advancing medicines wherever we
believe we can make a meaningful difference on the lives of patients.
Today, Pfizer Oncology has an industry-leading portfolio of 18 approved
innovative cancer medicines and biosimilars across more than 20
indications, including breast, prostate, kidney, lung and hematology.
Pfizer Oncology is striving to change the trajectory of cancer.

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, 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 @Pfizer_News, LinkedIn,
YouTube,
and like us on Facebook at Facebook.com/Pfizer.

DISCLOSURE NOTICE:

The information contained in this release is as of April 3, 2019.
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 VIZIMPRO
(dacomitinib), a kinase inhibitor, and an approval by the European
Commission, including their potential benefits, that involve 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
clinical endpoints, commencement and/or completion dates for our
clinical trials, regulatory submission dates, regulatory approval dates
and/or launch dates, as well as the possibility of unfavorable new
clinical data and further analyses of existing clinical data; the risk
that clinical trial data are subject to differing interpretations and
assessments by regulatory authorities; whether regulatory authorities
will be satisfied with the design of and results from our clinical
studies; whether and when applications for VIZIMPRO may be filed in
other jurisdictions; whether and when any such other applications for
VIZIMPRO that may be pending or filed may be approved by regulatory
authorities, which will depend on myriad factors, including making a
determination as to whether the product’s benefits outweigh its known
risks and determination of the product’s efficacy and, if approved,
whether VIZIMPRO will be commercially successful; decisions by
regulatory authorities impacting labeling, manufacturing processes,
safety and/or other matters that could affect the availability or
commercial potential of VIZIMPRO; 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, 2018 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 VIZIMPRO® (dacomitinib). Summary of Product
Characteristics.]

² Pfizer. Data on File.

³ Lovly CM, Horn L. Molecular profiling of lung cancer.
My Cancer Genome; 2016. https://www.mycancergenome.org/content/disease/lung-cancer/.
Accessed January 2019.

⁴ Pao W, Miller VA. Epidermal growth factor receptor
mutations, small-molecule kinase inhibitors, and non-small-cell lung
cancer: current knowledge and future directions. J Clin Oncol.
2005;23:2556-2568.