MEDIA RELEASE PR41847
New Phase 4 Study Shows Higher Rates of Clinical and Microbiological Success for Zyvox Versus
Vancomycin in MRSA Nosocomial Pneumonia
NEW YORK, Oct. 21 /PRNewswire-AsiaNet/ --
Findings From Largest MRSA Nosocomial Pneumonia Study Conducted
to Date Were Presented During IDSA Annual Meeting
Results of a new international phase 4 study of patients with nosocomial
pneumonia due to proven methicillin-resistant Staphylococcus aureus (MRSA)
demonstrated that the antibiotic Zyvox(R) (linezolid) achieved a
statistically significantly higher clinical success rate compared with
vancomycin for the primary endpoint. The ZEPHyR (Linezolid in the treatment
of subjects with nosocomial pneumonia proven to be due to
methicillin-resistant Staphylococcus aureus) study was the largest ever
conducted in this population. These findings will be presented at the 48th
Annual Meeting of the Infectious Diseases Society of America in Vancouver.
Investigators from 156 centers worldwide randomized 1,225 patients, of
whom 448 patients had proven MRSA nosocomial pneumonia (modified
intent-to-treat group); 339 patients also met key protocol criteria at the
end of study (per-protocol group) and were included in the primary analysis.
Clinical success rates at the end of study were 57.6 percent (95/165) for
patients treated with Zyvox compared with 46.6 percent (81/174) for patients
treated with vancomycin in the per-protocol group, the primary endpoint.
These results demonstrated that Zyvox achieved a statistically significantly
higher clinical success rate compared to vancomycin (95 percent confidence
interval for the difference in response rates: 0.5 percent, 21.6 percent;
p=0.042). Results were consistent for the per-protocol group at end of
treatment and for all MRSA pneumonia subjects (modified intent-to-treat) at
end of treatment and end of study. Microbiologic success was also consistent
in both the per-protocol and the modified intent-to-treat groups at both end
of treatment and end of study.
"Nosocomial pneumonia continues to be a significant cause of illness, and
when these infections are due to MRSA, our options are limited, as there are
few antibiotics that are effective against this resistant organism," said
study investigator Dr. Jean Chastre, Professor of Medicine and Critical Care
Medicine, University Paris 6, Reanimation Medicale, Pitie-Salpetriere
Hospital, Paris. "The findings, which show a higher cure rate for linezolid
compared with vancomycin, provide important information for physicians who
treat nosocomial pneumonia caused by MRSA."
An estimated 1.7 million healthcare-associated infections are reported in
U.S. hospitals annually,(1) and about 16 percent of those are associated with
pathogens that are resistant to the antimicrobials traditionally used to
treat them, including MRSA.(2) In a review of invasive MRSA cases reported in
nine U.S. communities participating in the Centers for Disease Control and
Prevention's Active Bacterial Core surveillance program,
healthcare-associated pneumonia accounted for between 12 percent and 16
percent of all healthcare-associated invasive MRSA infections.(3)
"Pfizer is committed to research in infectious diseases, and data from
this large comparative study add to the body of evidence for Zyvox in the
treatment of MRSA nosocomial pneumonia and reinforce its efficacy in this
patient population," said Dr. Mark Kunkel, Executive Director, Clinical Group
Lead for Anti-infective Drugs, Specialty Care Business Unit, Pfizer (NYSE:
PFE).
Safety data were assessed in all patients who received at least one dose
of study drug, the intent-to-treat group (N=1,184). Treatment-related adverse
events, serious adverse events and deaths were comparable for Zyvox and
vancomycin. Adverse events were considered treatment-related for 16.2 percent
of Zyvox patients and 18.4 percent of vancomycin subjects. Treatment-related
adverse events reported in 1 percent or more of Zyvox patients were diarrhea
(3.7 percent), rash (2.7 percent), constipation (1.0 percent) and nausea (1.0
percent). Treatment-related adverse events reported in 1 percent or more of
vancomycin patients were diarrhea (4.3 percent), nausea (1.9 percent), rash
(1.7 percent), anemia (1.4 percent) and acute renal failure (1.4 percent).
Overall, 208 patients in each group reported serious adverse events; these
were considered treatment-related in five Zyvox patients and 13 vancomycin
patients. Deaths occurred in 18.3 percent of patients who received Zyvox and
19.4 percent of patients who received vancomycin.
More About the ZEPHyR Study
This phase 4, randomized, double-blind, multicenter trial compared the
efficacy and safety of Zyvox with vancomycin in the treatment of nosocomial
pneumonia proven to be caused by MRSA, a serious and difficult-to-treat
bacterial infection that is resistant to many antibiotics. The study
randomized 1,225 patients between 2004 and 2010. The study was designed as a
non-inferiority study with nested superiority, meaning the primary endpoint
would be tested for superiority if it met non-inferiority criteria. In the
study, Zyvox was non-inferior and statistically superior to vancomycin in
achieving both clinical and microbiologic success. The primary endpoint was
clinical outcome at end of study in the per-protocol population. Secondary
analyses included clinical outcome at end of treatment in the per-protocol
population, clinical outcomes in the modified intent-to-treat population at
end of study and end of treatment, microbiologic outcomes at end of study and
end of treatment in the per-protocol and modified intent-to-treat
populations, and safety and tolerability in the intent-to-treat population.
Patients were randomized to receive Zyvox IV 600 mg every 12 hours or
vancomycin 15 mg/kg every 12 hours over the course of seven to 14 days;
vancomycin doses could be titrated at the investigator's discretion based on
creatinine clearance and vancomycin trough levels.
About Zyvox
Zyvox is the first and only approved treatment from the oxazolidinone
class of antibiotics. Zyvox inhibits bacterial protein synthesis through a
mechanism of action that is different from that of other antibacterial
agents, making cross-resistance between Zyvox and other classes of
antibiotics unlikely. To date, more than 4 million patients worldwide have
been treated with Zyvox.(4)
Zyvox is indicated in the treatment of the following infections caused by
susceptible strains of the designated microorganisms:
- Nosocomial pneumonia caused by Staphylococcus aureus
(methicillin-susceptible and -resistant strains) or Streptococcus
pneumoniae (including multi-drug resistant strains [MDRSP]).
- Complicated skin and skin structure infections, including
diabetic foot infections, without concomitant osteomyelitis, caused by
Staphylococcus aureus (methicillin-susceptible and -resistant strains),
Streptococcus pyogenes, or Streptococcus agalactiae. Zyvox has not been
studied in the treatment of decubitus ulcers.
- Vancomycin-resistant Enterococcus faecium infections, including cases
with concurrent bacteremia.
- Uncomplicated skin and skin structure infections caused by
Staphylococcus aureus (methicillin-susceptible only) or Streptococcus
pyogenes.
- Community-acquired pneumonia caused by Streptococcus pneumoniae
(including multi-drug resistant strains [MDRSP]), including cases with
concurrent bacteremia, or Staphylococcus aureus (methicillin-
susceptible strains only).
To reduce the development of drug-resistant bacteria and maintain the
effectiveness of Zyvox and other antibacterial drugs, Zyvox should be used
only to treat or prevent infections that are proven or strongly suspected to
be caused by susceptible bacteria. When culture and susceptibility
information are available, they should be considered in selecting or
modifying antibacterial therapy. In the absence of such data, local
epidemiology and susceptibility patterns may contribute to the empiric
selection of therapy.
Important Safety Information
Zyvox use is contraindicated in patients with known hypersensitivity to
linezolid or any of the other product components.
Zyvox should not be used in patients taking any medicinal product which
inhibits monoamine oxidases A or B (e.g. phenelzine, isocarboxazid) or within
2 weeks of taking any such product.
Unless patients are monitored for potential increases in blood pressure,
Zyvox should not be administered to patients with uncontrolled hypertension,
pheochromocytoma, thyrotoxicosis and/or patients taking any of the following:
directly and indirectly acting sympathomimetic, vasopressive, and
dopaminergic agents.
Unless patients are carefully observed for signs and/or symptoms of
serotonin syndrome, Zyvox should not be administered to patients with
carcinoid syndrome and/or patients taking any of the following medications:
serotonin reuptake inhibitors, tricyclic antidepressants, serotonin 5HT1
receptor agonists, meperidine, or buspirone.
Spontaneous reports of serotonin syndrome have been reported with the
co-administration of Zyvox and serotonergic agents. If signs or symptoms of
serotonin syndrome, such as cognitive dysfunction, hyperpyrexia,
hyperreflexia, and incoordination occur, discontinuation of one or both
agents should be considered.
Myelosuppression (including anemia, leukopenia, pancytopenia, and
thrombocytopenia) has been reported in patients receiving Zyvox. In cases
where the outcome is known, when Zyvox was discontinued, the affected
hematologic parameters returned to pretreatment levels. Complete blood counts
should be monitored weekly, particularly in patients who receive Zyvox for
longer than 2 weeks.
Zyvox is not approved and should not be used for the treatment of
patients with catheter-related bloodstream infections or catheter-site
infections.
Zyvox has no clinical activity against Gram-negative pathogens and is not
indicated for the treatment of Gram-negative infections. It is critical that
specific Gram-negative therapy be initiated immediately if a concomitant
Gram-negative pathogen is documented or suspected.
Clostridium difficile associated diarrhea has been reported with use of
nearly all antibacterial agents, including Zyvox, and may range in severity
from mild diarrhea to fatal colitis.
Lactic acidosis has been reported with the use of Zyvox. Patients
receiving Zyvox who develop recurrent nausea, vomiting, unexplained acidosis,
or a low bicarbonate level should receive immediate medical evaluation.
Peripheral and optic neuropathy have been reported primarily in patients
treated with Zyvox for longer than the maximum recommended duration of 28
days. If patients experience symptoms of visual impairment, prompt ophthalmic
evaluation is recommended.
Convulsions have been reported in patients treated with Zyvox. In some of
these cases, a history of seizures or risk factors for seizures was reported.
The most commonly reported adverse events in adults across phase 3
clinical trials were diarrhea, nausea and headache.
Pfizer Inc.: Working together for a healthier world(TM)
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and well-being at every stage of life. We strive to set the standard for
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About Pfizer's Specialty Care Business
Pfizer's Specialty Care Business Unit and Emerging Markets Specialty Care
Commercial Unit bring together an impressive team of colleagues who are
experts in their fields, a successful portfolio of market-leading, in-line
medicines and a rich pipeline of promising new compounds.
With approximately $7.3 billion in global revenue (first six months
2010), Pfizer continues to be the world's largest specialty pharmaceuticals
business, with a commitment to the eradication, remission and relief of
serious disease. Pfizer's Specialty Care Business is committed to bringing
together the best scientific minds to challenge the most feared diseases of
our time. We have a robust portfolio of therapies to treat rare diseases,
including hemophilia, pulmonary hypertension and specific endocrine
disorders.
DISCLOSURE NOTICE: The information contained in this release is as of
October 21, 2010. 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 Zyvox that
involves substantial risks and uncertainties. Such risks and uncertainties
include, among other things, the uncertainties inherent in research and
development; decisions by regulatory authorities regarding labeling and other
matters that could affect the availability or commercial potential of Zyvox;
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, 2009 and in
its reports on Form 10-Q and 8-K.
(1) Klevens RM, Edwards JR, Richards CL Jr, et al. Estimating health
care-associated infections and deaths in US hospitals, 2002. Public Health
Rep. 2007;122(2):160-166.
(2) Hidron AI, Edwards JR, Patel J, et al; National Healthcare Safety
Network Team; Participating National Healthcare Safety Network Facilities.
NHSN annual update: antimicrobial-resistant pathogens associated with
healthcare-associated infections: annual summary of data reported to the
National Healthcare Safety Network at the Centers for Disease Control and
Prevention, 2006-2007. Infect Control Hosp Epidemiol. 2008;29(11):996-1011.
(3) Klevens RM, Morrison MA, Nadle J. Invasive methicillin-resistant
Staphylococcus aureus infections in the United States. JAMA. 2007;298(15
):1763-1771.
(4) Data on file. Pfizer Inc, New York, NY.
SOURCE Pfizer Inc.
CONTACT: Media: Curtis Allen,
+1-212-733-2096 office,
+1-347-443-5252 mobile, or
Investor: Suzanne Harnett,
+1-212-733-8009,
both of Pfizer Inc.
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