Pivotal Phase III Study Underscores Efficacy Of Zavicefta™ (ceftazidime-avibactam) For Treatment Of Hospital-Acquired Pneumonia, A Leading Cause Of Mortality In Hospitals

NEW YORK–(BUSINESS WIRE)– Positive results of the REPROVE¹ Study showed that patients
diagnosed with hospital-acquired pneumonia (HAP), treated with
Zavicefta, a novel combination antibiotic for the treatment of certain
known or suspected Gram-negative bacterial infections, or Meropenem
(meropenem for injection), a broad spectrum carbapenem antibiotic
currently considered the standard of care, experienced comparable rates
of clinical cure at test-of-cure 21-25 days after randomization.
Clinical cure was the primary endpoint of the study and defined as a
complete resolution of all signs and symptoms of infection.

In addition, patients treated with Zavicefta and Meropenem experienced
comparable rates of tolerability consistent with the known profile of
ceftazidime alone. The results of the REPROVE study were presented today
at the 27^th annual meeting of the European Congress of
Clinical Microbiology and Infectious Disease (ECCMID) in Vienna.

“Hospital-acquired pneumonia has become more prevalent and difficult to
treat because of the emergence of increased resistance to carbapenems
thereby limiting treatment options,” said Professor Antoni Torres, MD,
PhD, FERS, Respiratory Institute, Hospital Clinic of Barcelona,
University of Barcelona, Spain and lead investigator of REPROVE. “These
study results expand physician options in effectively treating patients
with hospital-acquired pneumonia.”

“The REPROVE results validate the use of Zavicefta for the treatment of
certain Gram-negative infections among patients with limited treatment
options,” said Jill Inverso, Vice President of Pfizer Global Medical
Affairs, Critical Care Medicines. “The recent introduction of Zavicefta
in select European Markets together with planned future global launches
reaffirms our continued commitment to the delivery of new antibiotic
therapies that address the needs of patients with serious infections.”

REPROVE Top-Line Results

REPROVE was a Phase III, prospective, multi-center, randomized,
non-inferiority trial to assess the efficacy, safety and tolerability of
Zavicefta (ceftazidime-avibactam) administered intravenously as a
two-hour infusion (2000mg/500mg every 8 hours) as compared to Meropenem
(meropenem for injection) administered intravenously as a 30-minute
infusion (1000mg every 8 hours) among adult patients with clinically
diagnosed HAP or ventilator-associated pneumonia (VAP). The study
included 879 patients in 23 countries.

Results showed that patients treated with Zavicefta experienced
statistically equivalent rates of clinical cure 21-25 days from
randomization in both the clinically modified intent-to-treat (cMITT²)
population and clinically evaluable (CE³) population. More
specifically, clinical cure rates in the cMITT population and the CE
population treated with Zavicefta were 68.8 percent and 77.4 percent,
respectively, compared to clinical cure rates of 73.0 percent and 78.1
percent in the meropenem treatment arm. Similar efficacy was observed in
a subgroup analysis of VAP patients in both the cMITT and CE populations.

All-cause mortality rate at day 28 from randomization was also similar
in the two groups. Safety and tolerability observations for
ceftazidime-avibactam were consistent with the comparator and the known
profile for ceftazidime alone.

About Hospital-Acquired Infections (HAI)

A hospital-acquired infection (HAI), also known as a nosocomial
infection, is an infection
that is acquired in a hospital
or other healthcare facility and includes severe pneumonia, infections
of the urinary tract, bloodstream or other parts of the body. According
to the European Center for Disease Prevention and Control, approximately 1
in 18 of the people admitted to a hospital will contract an
HAI. Hospital-acquired pneumonia (HAP), an infection of the lungs, is
the second most common nosocomial infection and a leading cause of death
in intensive care units. Signs and symptoms of HAP include cough,
dyspnea (shortness of breath) fever, chills, and chest pain. The most
common cause of HAI and HAP are Gram-negative bacteria, which have
become increasingly resistant to many available antibiotic treatments.

In June 2016, the European Medicines Agency approved the marketing
authorization for Zavicefta. Zavicefta is indicated for the treatment of
adults with complicated intra-abdominal infection (cIAI), complicated
urinary tract infection (cUTI) and hospital-acquired pneumonia (HAP),
including ventilator- associated pneumonia (VAP). Zavicefta is also
indicated for the treatment of infections due to aerobic Gram-negative
organisms in adult patients with limited treatment options. Pfizer
recently launched Zavicefta in the UK, Germany and Austria.

About Pfizer Anti-Infectives

Since its pioneering work on penicillin in the 1940s, Pfizer has been
actively engaged in the research and development of innovative
medicines, policies and educational programs to address the evolving
needs of patients and physicians in the area of infectious diseases.

For more than 30 years, Pfizer has been a leader in developing and
implementing innovative public-private partnerships designed to address
unmet medical needs and global public health issues. Today, our patient
assistance programs expand access of potentially lifesaving medicines
and provide educational resources that empower patients and physicians
in the fight against infectious disease. Click here
to learn more.

About Zavicefta

Zavicefta (ceftazidime-avibactam) is a fixed-dose combination
antibacterial that was developed to treat serious Gram-negative
bacterial infections. It consists of a combination of avibactam and
ceftazidime – a third-generation antipseudomonal cephalosporin with a
well-established efficacy and safety profile. Avibactam is a
first-in-class broad-spectrum β-lactamase inhibitor, which protects
ceftazidime against degradation by Ambler class A, C and some D,
β-lactamases. Zavicefta has demonstrated in vitro activity against a
broad range of isolates of carbapenem-resistant Enterobacteriaceae
(CRE), including Klebsiella pneumonia carbapenemase
(KPC)-producing bacteria, and difficult to treat Pseudomonas
aeruginosa, combined with robust coverage against extended spectrum
β-lactamase (ESBL) expressing Gram negative pathogens. Avibactam does
not inhibit Ambler class B enzymes (metallo-β-lactamases) and is not
able to inhibit many of the class D enzymes.

Pfizer holds the global rights to commercialize Zavicefta, with the
exception of North America (U.S. and Canada), where the rights are held
by Allergan.

Important Zavicefta Safety Information

In clinical studies, ceftazidime-avibactam was proven to be as effective
as current carbapenem standards of care in the treatment of serious
aerobic Gram-negative infections, including in patients with infections
caused by ceftazidime-resistant bacteria. The most common adverse events
occurring in 5% or more of patients (n=2024 from seven Phase 2 and 3
clinical trials) treated with ceftazidime-avibactam included: the
presence of antibodies that cause red blood cells to die early (positive
Coombs direct test), nausea and diarrhea. There was no evidence of
hemolysis in patients who developed a positive Coombs direct test in
patient enrolled in clinical studies, however there remains a potential
risk. Nausea and diarrhea were usually mild or moderate in intensity.

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world™

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DISCLOSURE NOTICE: The information contained in this release
is as of April 24, 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 regarding Zavicefta
(ceftazidime-avibactam), launch plans and Pfizer’s anti-infectives
portfolio, 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 Zavicefta; the uncertainties inherent in
research and development; whether and when any drug applications may be
filed in any additional jurisdictions for Zavicefta; whether and when
regulatory authorities in any such other jurisdictions where
applications may be filed or pending may approve such applications,
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 Zavicefta; 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 Randomized, MultiCentre Study of Ceftazidime-Avibactam
versus Meropenem in Adults with Nosocomial Pneumonia Including
Ventilator Associated Pneumonia
² cMITT
is defined as patients enrolled in the study who were infected with a
target bacteria.
³ CE is
defined as patients in the cMITT who also completed therapy and whose
treatment followed the protocol for the study.

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