New Phase 4 Study Shows Higher Rates Of Clinical And Microbiological Success For Zyvox Versus Vancom

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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)

    At Pfizer, we apply science and our global resources to improve health

and well-being at every stage of life. We strive to set the standard for

quality, safety and value in the discovery, development and manufacturing of

medicines for people and animals. Our diversified global health care

portfolio includes human and animal biologic and small molecule medicines and

vaccines, as well as nutritional products and many of the world's best-known

consumer 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 the world's leading biopharmaceutical company, we also

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, Pfizer has worked to make a difference for

all who rely on us. To learn more about our commitments, please visit us at



    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

Misc Miscellaneous Pfizer Inc. 3 image

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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