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Positive Study Results for Ceftaroline Phase III Clinical Study for the Treatment of Complicated Skin and Skin Structure Infections Presented at ICAAC / IDSA

October 27, 2008

WASHINGTON, Oct. 27, 2008 /PRNewswire-FirstCall/ — Forest Laboratories, Inc. 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)

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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 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.

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Forest Laboratories, Inc.

CONTACT: Frank J. Murdolo, Vice President – Investor Relations, ForestLaboratories, Inc., +1-212-224-6714, Frank.Murdolo@frx.com

Web Site: http://www.frx.com/




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