New Data on Ceftaroline, a Novel, Broad-Spectrum Cephalosporin in
Development for Complicated Skin and Skin Structure Infections (cSSSI) and
Community Acquired Pneumonia (CAP)
WASHINGTON, Oct. 27, 2008 /PRNewswire-FirstCall/ -- Forest
Laboratories, Inc. (NYSE: FRX) presented a detailed analysis of CANVAS I, a
globally conducted, multi-center, Phase III clinical trial, at the 48th
Annual Interscience Conference on Antimicrobial Agents and Chemotherapy /
Infectious Diseases Society of America 46th Annual Meeting (ICAAC / IDSA)
in Washington, DC. The results of this 702 patient study demonstrated that
ceftaroline monotherapy achieved its primary endpoint of non-inferiority
versus the combination of vancomycin and aztreonam in the treatment of
complicated skin and skin structure infections (cSSSI).(1)
(LOGO: http://www.newscom.com/cgi-bin/prnh/20001011/FORESTLOGO )
Forest also presented eighteen abstracts on data from preclinical
studies that demonstrate the activity of ceftaroline against
methicillin-resistant Staphylococcus aureus (MRSA), multi-drug resistant
Streptococcus pneumoniae (MDRSP) and many gram-negative pathogens in both
in vitro and in vivo models of infection.
Results of the CANVAS I study presented on Sunday show that
ceftaroline-treated patients had a clinical cure rate of 91.1% compared to
a vancomycin-plus-aztreonam clinical cure rate of 93.3% at the test of cure
(TOC) visit in the clinically evaluable population (CE). In the
modified-intent-to-treat (MITT) population, ceftaroline-treated patients
had a clinical cure rate of 86.6% compared to a vancomycin-plus-aztreonam
clinical cure rate of 85.6%. The study was designed to achieve a
non-inferiority margin of 10% for ceftaroline versus the comparator regimen
for the above endpoints. The most common infections included deep,
extensive cellulitis and major abscesses. The percent of patients with
diabetes and peripheral vascular disease in the ceftaroline arm was 17.7%
and 13.4%, respectively.(1) 30% of patients with a confirmed pathogen had a
MRSA infection.
The most common pathogens isolated were S. aureus (MSSA and MRSA),
Streptococcus pyogenes, Streptococcus agalactiae, Enterococcus faecalis, E.
coli and P. aeruginosa. A comprehensive microbiological investigation was
completed and ceftaroline demonstrated activity against a broad range of
gram-positive pathogens and gram-negative pathogens. Microbiological
eradication rates for ceftaroline alone were similar to those of the
combination of vancomycin plus aztreonam (91.8% vs. 92.5%). MRSA
eradication rates were also similar in the microbiologically evaluable
patients in the ceftaroline and combination arms (94.9% vs. 91.8%).
"These new data add to the growing scientific evidence that support
ceftaroline as a potential novel treatment for cSSSIs, including those
caused by MRSA," said G. Ralph Corey, MD, Director, Infectious Diseases,
Duke Clinical Research Institute. "These results are important because we
see a growing number of infections, including many with difficult-to-treat
organisms. Clearly new options are needed to optimize our current treatment
capabilities."
The results of CANVAS I also demonstrate that ceftaroline was well
tolerated. The majority of adverse events reported were mild and judged to
be not treatment related. The percentage of patients who experienced an
adverse event was similar in both treatment groups. The most common adverse
events observed in the ceftaroline vs. vancomycin-plus-aztreonam arms were
nausea (5.7% vs. 4.6%), headache (5.1% vs. 3.7%) and pruritis (3.1% vs.
8.4%).(1)
The data presented from CANVAS I demonstrate that ceftaroline, as
monotherapy, is highly efficacious and well tolerated in treating cSSSIs.
Ceftaroline demonstrated efficacy in a variety of monomicrobial and
polymicrobial infections including those with challenging pathogens and
drug-resistant phenotypes. The full results from this study demonstrate
that ceftaroline's efficacy as monotherapy is similar to combination
therapy with vancomycin and aztreonam.
"We're very pleased with the data presented which corroborate
ceftaroline's potential use for the treatment of complicated skin
infections, including those caused by MRSA - a common yet highly serious
and growing problem faced by hospitalized patients today," Marco Taglietti,
Chief Medical Officer of the Forest Research Institute, explained. "We are
committed to investing in highly effective therapies, such as ceftaroline,
to treat the growing number of multi-drug resistant infections. Along with
this commitment, it is our intent to build a novel and robust antimicrobial
franchise."
Phase III Study Design
CANVAS I, a globally conducted, multi-center, Phase III, randomized,
double-blind comparative study was designed to evaluate the efficacy and
safety of ceftaroline as monotherapy compared to the combination of
vancomycin plus aztreonam.(1) The data were collected from 702 adult
patients with cSSSIs caused by gram-positive and/or gram-negative
bacteria.(1)
Highlights of additional data presented at ICAAC / IDSA include the
following:
--Ceftaroline activity tested against organisms causing skin and skin
structure infections (SSSIs) isolated in USA and European medical centers
in 2008 (Poster C1-160)(2)
--Antimicrobial activity of ceftaroline tested against contemporary
(2008) bacteria isolated from community-acquired respiratory tract
infections (CARTI), including oxacillin- (methicillin-) resistant
Staphylococcus aureus (MRSA) (Poster C2-1974)(3)
Dr. R. Jones and colleagues presented two sets of surveillance data
examining ceftaroline in vitro activity against isolates from cSSSI and
CAP. Ceftaroline was highly active against over 1,500 gram-positive
pathogens isolated from cSSSI in the US and Europe, including
methicillin-resistant Staphylococcus aureus (MRSA) and
fluoroquinolone-resistant streptococci, thus, providing strong support for
the use of this agent in the treatment of complicated skin infections.
Furthermore, it was found to be highly active against more than 500
community-acquired respiratory tract clinical isolates, including
difficult-to-treat antibiotic-resistant strains.(2,3)
--Activities of ceftaroline, ceftobiprole, and cethromycin against
multi-drug-resistant (MDR) Streptococcus pneumoniae isolates from Canadian
Bacterial Surveillance Network (CBSN) (Poster C1-3843)(4)
Dr. D. Low and colleagues from the Canadian Bacterial Surveillance
Network report that three new antibiotics, cethromycin, ceftaroline, and
ceftobiprole, have greater in vitro activity against MDRSP than
ceftriaxone. Ceftaroline was eight-fold more active than ceftriaxone and
four-fold more active than ceftobiprole against these resistant pathogens,
supporting its use in potentially life-threatening infections caused by
these bacteria.(4)
--In vitro activity of ceftaroline (CPT) vs. vancomycin (VM) against
MRSA and hVISA strains in a pharmacokinetic/pharmacodynamic (PK/PD) model
(Poster A-979)(5)
--In vitro activity of ceftaroline against CA-MRSA, VISA, VRSA and
daptomycin-non-susceptible Staphylococcus aureus (DNSSA) (Poster C1-162)(6)
Dr. C. Vidaillac and colleagues used an in vitro model system to
compare the activity of ceftaroline with vancomycin. Ceftaroline was more
active against a S. aureus strain with intermediate susceptibility to
vancomycin and showed similar or superior activity against MRSA, suggesting
that it may provide a new option for the treatment of antibiotic-resistant
S. aureus.(5) In support, Dr. L. Saravolatz and colleagues showed that
ceftaroline has the greatest overall in vitro bactericidal activity against
community-associated MRSA (CA-MRSA), vancomycin-intermediate S. aureus
(VISA), vancomycin-resistant S. aureus (VRSA) and daptomycin
non-susceptible S. aureus (DNSSA) compared to vancomycin, daptomycin,
clindamycin, linezolid, TMP/SMX, and ceftriaxone.(6)
--Spontaneous mutation frequency and serial passage resistance
development studies with ceftaroline (CPT) (Poster C1-185)(7)
Dr. R. Hinshaw and colleagues evaluated the risk of ceftaroline
resistance development using an in vitro model. There was no propensity for
resistance development to ceftaroline when serially tested against
important skin and community-acquired pneumonia pathogens, including
methicillin-susceptible S. aureus (MSSA), MRSA, community-acquired MRSA
(CA-MRSA), vancomycin-intermediate S. aureus (VISA), penicillin-susceptible
S. pneumoniae (PSSP), penicillin-resistant S. pneumoniae (PRSP), and
beta-lactamase-negative H. influenzae.(7)
About Complicated Skin and Skin Structure Infections (cSSSIs)
cSSSIs are caused by gram-positive bacteria, such as MRSA, and common
gram-negative bacteria.(8) cSSSIs are among the most common infections
treated in the hospital setting,(9) and MRSA infections, now the most
frequent cause of cSSSI presenting to emergency departments in the United
States (U.S.) and the cause of more than 18,000 deaths in 2005, are
becoming more common in patients in both the hospital and community
settings.(10)
According to the Centers for Disease Control and Prevention, about 70%
of bacterial infections are resistant to at least one drug.(11) Many are
resistant to multiple drugs making cSSSIs, especially due to MRSA,
challenging to treat.(12) cSSSIs can become extremely serious, leading to
hospitalization with increased risk for morbidity and mortality and
increased healthcare costs.(11) In a study of patients in the emergency
room with skin and skin-structure infections, S. aureus was isolated from
76% of patients, and more than half were MRSA.(13)
About Ceftaroline
Ceftaroline is a novel, bactericidal, injectable, broad-spectrum
cephalosporin being developed as a therapeutic agent for the treatment of
gram-positive pathogens, including MRSA and multi-drug resistant
Streptococcus pneumoniae (MDRSP), as well as common gram-negative
organisms. Ceftaroline has also demonstrated bactericidal activity against
vancomycin-resistant Staphylococcus aureus (VRSA), linezolid-resistant
Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae
(PRSP). Ceftaroline is a member of the cephalosporin class of antibiotics,
the most frequently prescribed class of antibiotics in the world.
Ceftaroline is also being studied in Phase III clinical trials for
community-acquired pneumonia.
About Forest Laboratories
Forest Laboratories (NYSE: FRX) is a U.S.-based pharmaceutical company
with a long track record of building partnerships and developing and
marketing products that make a positive difference in people's lives. In
addition to its well-established franchises in therapeutic areas of the
central nervous and cardiovascular systems, Forest's current pipeline
includes product candidates in all stages of development and across a wide
range of therapeutic areas. The company is headquartered in New York, NY.
To learn more about Forest Laboratories, visit http://www.FRX.com.
Except for the historical information contained herein, this release
contains forward-looking statements within the meaning of the Private
Securities Litigation Reform Act of 1995. These statements involve a number
of risks and uncertainties, including the difficulty of predicting FDA
approvals, the acceptance and demand for new pharmaceutical products, the
impact of competitive products and pricing, the timely development and
launch of new products, and the risk factors listed from time to time in
Forest Laboratories' Annual Report on Form 10-K, Quarterly Report on Form
10-Q, and any subsequent SEC filings.
Source: Forest Laboratories, Inc.
References
1. Corey R, Wilcox M, Talbot GH, et al. CANVAS-1: Randomized,
Double-blinded, Phase 3 Study (P903-06) of the Efficacy and Safety of
Ceftaroline vs. Vancomycin plus Aztreonam in Complicated Skin and Skin
Structure Infections (cSSSI). To be presented at ICAAC / IDSA 2008.
2. Jones RN, Fritsche TR, Sader HS. Ceftaroline activity tested against
organisms causing skin and skin structure infections (SSSIs) isolated in
USA and European medical centers in 2008 (Poster C1-160). To be presented
at ICAAC / IDSA 2008.
3. Sader HS, Fritsche TR, Jones RN. Antimicrobial activity of
ceftaroline tested against contemporary (2008) bacteria isolated from
community-acquired respiratory tract infections (CARTI), including
oxacillin-resistant S. aureus (MRSA) (Poster C2-1974).To be presented at
ICAAC / IDSA 2008.
4. Patel SN, McGeer A, Green K,et al. Activities of cethromycin (CETH),
ceftaroline (CPT), and ceftobiprole (BPR) against multi-drug resistant
(MDR) Streptococcus pneumoniae (SP) isolates from Canadian Bacterial
Surveillance Network (CBSN) (Poster C1-3843). To be presented at ICAAC /
IDSA 2008.
5. Vidaillac C, Leonard SN, Rybak MJ. In vitro activity of ceftaroline
(CPT) vs. vancomycin (VM) against MRSA and hVISA strains in a
pharmacokinetic/pharmacodynamic (PK/PD) model (Poster A-979). To be
presented at ICAAC / IDSA 2008.
6. Saravolatz LD, Pawlak J, Johnson L. In vitro activity of ceftaroline
against CA-MRSA, VISA, VRSA and daptomycin-non-susceptible Staphylococcus
aureus (DNSSA) (Poster C1-162). To be presented at ICAAC / IDSA 2008.
7. Hinshaw RR, Schaadt RD, Murray B, et al. Spontaneous mutation
frequency and serial passage resistance development studies with
ceftaroline (CPT) (Poster C1-185). To be presented at ICAAC / IDSA 2008.
8. DiNubile MJ, Lipsky BA. Complicated infections of skin and skin
structures: when the infection is more than skin deep. Journal of
Antimicrobial Chemotherapy (2004) 53, Suppl. S2, ii37-ii50.
9. Lee SY, Kuti JL, Nicolav DP. Antimicrobial management of complicated
skin and skin structure infections in the era of emerging resistance.
Surgical Infections. 2005, 6(3): 283-295.
10. Klevens RM, Morrison MA, et al. Invasive Methicillin-Resistant
Staphylococcus aureus Infections in the United States. JAMA. 2007; 298(15):
1763-1771.
11. U.S. Food and Drug Administration. Battle of the Bugs: Fighting
Antibiotic Resistance. Accessed on May 28, 2008. Available at:
http://www.fda.gov/fdac/special/testtubetopatient/antibiotics.html.
12. Scheinfeld N. Journal of Drugs in Dermatology. Jan 2007. A
comparison of available and investigational antibiotics for complicated
skin infections and treatment-resistant Staphylococcus aureus and
Enterococcus.
13. Moran, GJ. New England Journal of Medicine. Aug 2006.
Methicillin-Resistant S. aureus Infections among Patients in the Emergency
Department. 355:666-674.
SOURCE Forest Laboratories, Inc.
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Related links:
http://www.frx.com
Photo Notes:http://www.newscom.com/cgi-bin/prnh/20001011/FORESTLOGO
CONTACT:
Frank J. Murdolo, Vice President - Investor
Relations, Forest Laboratories, Inc., +1-212-224-6714,
Frank.Murdolo@frx.com
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