Late-Stage Anti-Infective, Ceftaroline, Achieved Primary Goal of Non-Inferiority and Achieved High Clinical Cure Rates in Adult Patients Hospitalized for Moderate to Severe CAP
Forest Laboratories, Inc (NYSE: FRX) today presented at the 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in San Francisco new data from a complete analysis of FOCUS 1 and FOCUS 2, two global multicenter Phase III studies of ceftaroline for the treatment of community-acquired pneumonia (CAP) in hospitalized patients. Detailed analyses from the previously reported top-line data of the two pivotal trials demonstrated that ceftaroline administered intravenously met the primary endpoint of non-inferiority in patients with moderate to severe CAP requiring hospitalization.1 Ceftaroline therapy was also generally well tolerated, with an adverse event profile similar to ceftriaxone.
CAP is a serious illness and common cause of mortality and morbidity. In the U.S. an estimated 5.6 million cases of CAP occur annually, resulting in an average of 4.5 million visits to physicians’ offices and as many as 1.1 million hospitalizations.2,3,4
Integrated Results
The randomized, double-blind, multicenter Phase III studies compared clinical outcomes following treatment with ceftaroline versus ceftriaxone in hospitalized adult patients with moderate to severe CAP.
The combined results of FOCUS 1 and FOCUS 2 demonstrated a clinical cure rate of 84.3% for ceftaroline and 77.7% for ceftriaxone in the integrated clinically evaluable (CE) patient population.The overall microbiological response rate in the microbiologically evaluable (ME) population was 87% for ceftaroline and 81% for ceftriaxone, and in the microbiological modified intent-to-treat (MITT) population it was 84.8% for ceftaroline and 80.4% for ceftriaxone.
“The robust data that have emerged from FOCUS 1 and 2 demonstrate that ceftaroline is a very promising new cephalosporin for the treatment of serious pneumonia in hospitalized patients,” said Dirk Thye, MD, President of Cerexa, the wholly owned anti-infectives subsidiary of Forest Laboratories, Inc. “The continuing medical need to deal with emerging resistance to existing therapeutic options is clear and urgent. These results, along with our prior positive results in complicated skin and skin structure infections (cSSSI)5, confirm that ceftaroline has unique properties allowing it to address this medical need. We intend to submit our New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for cSSSI and CAP around the end of this calendar year.”
In addition to these two pivotal studies for CAP, data on the microbiology of ceftaroline is being presented at ICAAC, demonstrating its bactericidal activity in vitro and in animals against a broad range of pathogens including those commonly implicated in both cSSSI and CAP, as well as MRSA and multi-drug resistant Streptococcus pneumoniae (MDRSP).
Posters
- Snydman DR, Jacobus NV, et al. In Vitro Activity of Ceftaroline vs a Broad Spectrum of Recent Clinical Anaerobic Isolates. Poster #903-M-060.6
- Citron DM, Goldstein EJC, et al. In Vitro Activity of Ceftaroline Against Anaerobic Bacteria. Poster #903-M-058.7
- Farrell DJ, Patel SN, et al. Activity of Ceftaroline (CPT) Against Recent Streptococcus pneumoniae (SP) Isolates From the Canadian Bacterial Surveillance Network (CBSN). Poster #903-M-067. 8
- Jacobs MR, Bajaksouzilan S, et al. Activity of Ceftaroline Against Emerging Serotypes of Streptococcus pneumoniae. Poster #903-M-069. 9
- Jones RN, Sader HS, et al. Antimicrobial Activity of Ceftaroline Tested against streptococci from United States (USA) and European (EU) Medical Centers: Results from the Ceftaroline Longitudinal Assessment of Spectrum and Susceptibility (CLASS) Program. Poster #0903-M-035.10
- Vidaillac C. Newton K, et al. Evaluation of Oxacillin, Daptomycin, and Ceftaroline Activity Against Clinical Vancomycin Heterovariant Methicillin-Resistant Staphylococcus aureus (MRSA). Poster #903-M-074.11
- Jacqueline C, Amador G, et al. Activity of Ceftaroline (CPT) vs Daptomycin (DAP), and Tigecycline (TGC) Against Methicillin-Susceptible, Methicillin-Resistant, and Glycopeptide-Intermediate Staphylococcus aureus: An Experimental Rabbit Endocarditis Study. Poster #903-M-042.12
- Sader HS, Mendes RE, et al. Antimicrobial Activity of Ceftaroline Tested Against Streptococci From United States (USA) and European (EU) Medical Centers: Results from the Ceftaroline Longitudinal Assessment of Spectrum and Susceptibility (CLASS) Program. Poster #0903-M-035.13
- Kosowska-Shick K, McGhee P, Appelbaum P. Affinity of Ceftaroline and Caparator b-lactams to Penicillin-Binding Proteins (PBPs) from Staphylococcus aureus. Poster #903-M-041.14
About Ceftaroline and Ceftaroline / NXL104
Ceftaroline is a novel, bactericidal, injectable, broad-spectrum cephalosporin being developed as a therapeutic agent for the treatment of cSSSI and CAP which include gram-positive pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant S. pneumoniae (MDRSP), as well as common gram-negative organisms. Ceftaroline has demonstrated antibacterial activity in vitro against vancomycin-resistant S. aureus (VRSA) and linezolid-resistant S. aureus. Ceftaroline is a member of the cephalosporin class of antibiotics, the most frequently prescribed class of antibiotics in the world. In clinical trials, ceftaroline has been generally well tolerated with an adverse event profile consistent with the cephalosporin class of antibiotics. Forest obtained the worldwide rights (excluding Japan, where Takeda Pharmaceuticals holds rights) to ceftaroline when it acquired Cerexa, Inc, a privately held biopharmaceutical company, in 2007. In August 2009, Forest Laboratories and AstraZeneca (NYSE:AZN) entered into a definitive collaboration agreement to co-develop and commercialize ceftaroline in all markets outside the U.S., Canada and Japan.
Forest is also developing a combination product consisting of ceftaroline and NXL104, a novel beta-lactamase inhibitor. The combination of NXL104 with ceftaroline enhances the in vitro antibacterial activity of ceftaroline against extended-spectrum beta-lactamase-producing (ESBL) gram-negative bacteria that are normally resistant to currently available broad-spectrum cephalosporins.
About CAP Requiring Hospitalization
In 2006, pneumonia, along with influenza, was the eighth leading cause of death in the U.S. and the number one cause of death in those over age 65.15,16The cost of care for patients with CAP in the U.S. has been estimated to be over $10 billion annually.17
The primary treatment for CAP is antibiotics14 and the rates of resistance to many commonly used antibiotics is increasing.18S. pneumoniae accounts for 60% to 70% of all bacterial CAP cases and data have shown that, overall, pneumococcal strains had a 28% intermediate resistance rate and a 16% high-level resistance rate.19 With increasing rates of pneumonia caused by MRSA and the high rates of resistance to common antibiotics, treatment options are becoming more limited.20
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 www.FRX.com. Cerexa, a wholly-owned subsidiary of Forest Laboratories, is a biopharmaceutical company focused on developing a growing portfolio of novel anti-infective therapies for the treatment of serious and life-threatening infections.
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 Reports on Form 10-Q, and any subsequent SEC filings.
References
1. Eckberg P, Friedland HD, et al. FOCUS 1 and 2: Randomized, Double-blinded, Multicenter Phase 3 Trials of the Efficacy and Safety of Ceftaroline (CPT) vs. Ceftriaxone (CRO) in Community-acquired pneumonia (CAP). Presentation L1-345a. Presented at ICAAC 2009.
2. Neiderman MS, McCombs JI, Inger AN, Kumar A, Popovian R. The cost of treating community-acquired pneumonia in the United States. JAMA. 1996; 275: 189-193.
3. Garibaldi RA. Epidemiology of community-acquired respiratory tract infections in adults: incidents, etiology and impact. Am J Med. 1985:78:32S-37S.
4. Centers for Disease Control and Prevention. Premature deaths, monthly mortality and monthly physicians contacts - United States. MMWR Morb Mortal Wkly Rep. 1997; 46:556.
5. 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). Presented at ICAAC / IDSA 2008.
6. Snydman DR, Jacobus NV, et al. In Vitro Activity of Ceftaroline vs a Broad Spectrum of Recent Clinical Anaerobic Isolates. Poster #903-M-060. Presented at ICAAC 2009.
7. Citron DM, Goldstein EJC, et al. In Vitro Activity of Ceftaroline Against Anaerobic Bacteria. Poster #903-M-058. Presented at ICAAC 2009.
8. Farrell DJ, Patel SN, et al. Activity of Ceftaroline (CPT) Against Recent Streptococcus pneumoniae (SP) Isolates From the Canadian Bacterial Surveillance Network (CBSN). Poster #903-M-067. Presented at ICAAC 2009.
9. Jacobs MR, Bajaksouzilan S, et al. Activity of Ceftaroline Against Emerging Serotypes of Streptococcus pneumoniae. Poster #903-M-069. Presented at ICAAC 2009.
10. Jones RN, Sader HS, et al. Antimicrobial Activity of Ceftaroline Tested against streptococci from United States (USA) and European (EU) Medical Centers: Results from the Ceftaroline Longitudinal Assessment of Spectrum and Susceptibility (CLASS) Program. Poster #0903-M-035 Presented at ICAAC 2009.
11. Vidaillac C. Newton K, et al. Evaluation of Oxacillin, Daptomycin, and Ceftaroline Activity Against Clinical Vancomycin Heterovariant Methicillin-Resistant Staphylococcus aureus (MRSA). Poster #903-M-074. Presented at ICAAC 2009.
12. Jacqueline C, Amador G, et al. Activity of Ceftaroline (CPT) vs Daptomycin (DAP), and Tigecycline (TGC) Against Methicillin-Susceptible, Methicillin-Resistant, and Glycopeptide-Intermediate Staphylococcus aureus: An Experimental Rabbit Endocarditis Study. Poster #903-M-042. Presented at ICAAC 2009.
13. Sader HS, Mendes RE, et al. Antimicrobial Activity of Ceftaroline Tested Against Streptococci From United States (USA) and European (EU) Medical Centers: Results from the Ceftaroline Longitudinal Assessment of Spectrum and Susceptibility (CLASS) Program. Poster #0903-M-035. Presented at ICAAC 2009.
14. Kosowska-Shick K, McGhee P, Appelbaum P. Affinity of Ceftaroline and Caparator b-lactams to Penicillin-Binding Proteins (PBPs) from Staphylococcus aureus. Poster #903-M-041 Presented at ICAAC 2009.
15. Centers for Disease Control and Prevention. National Center for Health Statistics. Deaths: Preliminary Data for 2005. September 2007.
16. Heron M, Hoyert D, Murphy S. National Vital Statistics Reports. Deaths: Final Data for 2006. 2009 April; 57:14. Available at: http://www.cdc.gov/nchs/data/nvsr/nvsr57/nvsr57_14.pdf. Accessed May 20, 2009.
17. Lave, JR, Lin CJ, Fine MJ, et al. The cost of treating patients with community-acquired pneumonia. Semin Respir Crit Care Med. 1999;20(3):189-97.
18. Official Statement of the American Thoracic Society. Guidelines for the Management of Adults with Community-acquired Pneumonia. Am J Repir Cric Care Med. 2001;163:1730-1754.
19. Lutfiyya MN, Henley E, Chang L. Diagnosis and Treatment of Community-Acquired Pneumonia. Am Fam Physician. 2006 Feb 1;73(3):442-50.
20. Mandell L. Wunderink A, Anzueto, J, et al. Infectious Diseases Society of America / America Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44:(Suppl. 2)S27-S72.
Contacts:
Forest Laboratories, Inc.
Frank J. Murdolo
Vice President,
Investor Relations
212-224-6714
Email: Frank.Murdolo@frx.com
