Pfizer’s Next-Generation ALK/ROS1 Inhibitor, Lorlatinib, Granted Breakthrough Therapy Designation from FDA for ALK-Positive Metastatic Non-Small Cell Lung Cancer

NEW YORK–(BUSINESS WIRE)– Pfizer Inc. today announced that its investigational next-generation
ALK/ROS1 tyrosine kinase inhibitor, lorlatinib, was granted Breakthrough
Therapy designation from the U.S. Food and Drug Administration (FDA) for
the treatment of patients with anaplastic lymphoma kinase (ALK)-positive
metastatic non-small cell lung cancer (NSCLC), previously treated with
one or more ALK inhibitors.

Enacted as part of the 2012 FDA Safety and Innovation Act (FDASIA),
Breakthrough Therapy designation is intended to expedite the development
and review of a potential new medicine if it is intended to treat a
serious or life-threatening disease and preliminary clinical evidence
indicates that the drug may demonstrate substantial improvement over
existing therapies.¹ The Breakthrough Therapy designation is
distinct from the FDA’s other mechanisms to expedite drug development
and review.² ALK gene rearrangement is a genetic alteration
that drives the development of lung cancer in some patients.^3,4
Due to additional mutations that the tumor may acquire during treatment,
disease progression remains a challenge in patients with ALK-positive
metastatic NSCLC.⁵

“This regulatory designation recognizes the potential for lorlatinib to
provide an important treatment option for patients with ALK-positive
NSCLC whose cancers have progressed despite treatment. Pfizer’s rapid
development of lorlatinib reflects a commitment to developing
biomarker-driven therapies to meet the evolving needs of patients,” said
Mace Rothenberg, MD, chief development officer, Oncology, Pfizer Global
Product Development. “We look forward to working with the FDA to
accelerate the development of this therapy.”

The Breakthrough Therapy designation is supported by the efficacy and
safety data of an ongoing Phase 1/2 clinical trial of lorlatinib, which
includes patients with ALK-positive NSCLC who were previously treated
with one or more ALK inhibitors.

Additionally, the Phase 3 CROWN study (NCT03052608) recently began
enrolling patients. CROWN is an ongoing, open label, randomized, two-arm
study comparing lorlatinib to crizotinib in the first-line treatment of
patients with metastatic ALK-positive NSCLC. Please visit clinicaltrials.gov
for more information on this study.

About Non-Small Cell Lung Cancer

Worldwide, lung cancer is the leading cause of cancer death in both men
and women.⁶ NSCLC accounts for about 85 percent of lung
cancer cases and remains difficult to treat, particularly in the
metastatic setting.⁷ Approximately 57 percent of NSCLC
patients are diagnosed late with metastatic, or advanced, disease where
the five-year survival rate is only 5 percent.⁸ NSCLC can be
further categorized into distinct subsets that are classified by a
number of factors, including histology and the molecular makeup of the
tumor. Epidemiology studies suggest that approximately 3 to 5 percent of
NSCLC tumors are ALK-positive.⁹

About Lorlatinib

Lorlatinib is an investigational next-generation ALK/ROS1 tyrosine
kinase inhibitor that has been shown to be highly active in preclinical
lung cancer models harboring chromosomal rearrangements of both ALK and
ROS1. Lorlatinib was specifically designed to inhibit tumor mutations
that drive resistance to other ALK inhibitors and to penetrate the blood
brain barrier. Lorlatinib is an investigational agent and has not
received regulatory approval for any indication anywhere in the world.

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

DISCLOSURE NOTICE: The information contained in this
release is as of April 27, 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 an
investigational oncology therapy, lorlatinib, 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, the uncertainties inherent in research and development,
including 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 and when any new drug applications may be filed in any
jurisdictions for lorlatinib; whether and when any such 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 lorlatinib; 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 U.S. Food and Drug
Administration Safety and Innovation Act. Available at: http://www.gpo.gov/fdsys/pkg/PLAW-112publ144/pdf/PLAW-112publ144.pdf.
Accessed April 26, 2017.
² U.S. Food and Drug
Administration Frequently Asked Questions: Breakthrough Therapies.
Available at:http://www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/SignificantAmendmentstotheFDCAct/FDASIA/ucm341027.htm.
Accessed March 16, 2015.
³ Chiarle R, Voena C, Ambrogio
C, et al. The anaplastic lymphoma kinase in the pathogenesis of cancer. Nat
Rev Cancer. 2008;8(1):11-23.
⁴ Guérin A, Sasane M,
Zhang J et al. ALK rearrangement testing and treatment patterns for
patients with ALK-positive non-small cell lung cancer. Cancer
Epidemiol. 2015 Jun;39(3):307-12. doi: 10.1016
⁵
Gainor et al. Molecular Mechanisms of Resistance to First- and
Second-Generation ALK Inhibitors in ALK-Rearranged Lung Cancer. Cancer
Discovery. 2016; 6(10): 1118-33.
⁶ The International
Agency for Research on Cancer, the World Health Organization, GLOBOCAN
2012, Available at: http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx.
Accessed October 15, 2015.
⁷ Reade CA, Ganti AK. EGFR
targeted therapy in non-small cell lung cancer: potential role of
cetuximab. Biologics. 2009; 3: 215 224.
⁸
National Cancer Institute. Surveillance, Epidemiology, and End Results
Program. Seer Stat Fact Sheets: Lung and Bronchus Cancer. http://seer.cancer.gov/statfacts/html/lungb.html.
Accessed October 15, 2015.
⁹ Garber K. ALK, lung cancer,
and personalized therapy: portent of the future? J Natl Cancer Inst.
2010; 102:672-675.

View source version on businesswire.com: http://www.businesswire.com/news/home/20170427005832/en/