Oritavancin

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Oritavancin
Systematic (IUPAC) name
(4R)-22-O-(3-Amino-2,3,6-trideoxy-3-C-methyl-alpha-L-arabinohexopyranosyl)-N3-(p-(p-chlorophenyl)benzyl)vancomycin
Identifiers
CAS number	171099-57-3
ATC code	?
PubChem	16131319
Chemical data
Formula	C86H97Cl3N10O26
Mol. mass	1793.1 g/mol
Pharmacokinetic data
Bioavailability	?
Metabolism	?
Half life	?
Excretion	?
Therapeutic considerations
Pregnancy cat.	?
Legal status
Routes	?

Oritavancin (INN, also known as LY333328) is a novel semi-synthetic glycopeptide antibiotic being developed for the treatment of serious Gram-positive infections. Originally discovered and developed by Eli Lilly, oritavancin was acquired by InterMune in 2001 and then by Targanta Therapeutics in late 2005^[1].

Contents 1 In Vitro Activity 2 Clinical Progress 3 NDA Submission 4 References

[edit] In Vitro Activity

Oritavancin shares certain properties with other members of the glycopeptide class of antibiotics, which includes vancomycin, the current standard of care for serious Gram-positive infections in the United States and Europe^[2]. Data presented at the 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in September 2007 demonstrated that oritavancin possesses potent and rapid bactericidal activity in vitro against a broad spectrum of both resistant and susceptible Gram positive bacteria, including Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Enterococci, and Streptococci^[3]. Two posters presented at the meeting also demonstrated that oritavancin was more active than either metronidazole or vancomycin against strains of Clostridium difficile tested^[4]. In addition, research was conducted in partnership with the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) and presented at the American Society for Microbiology (ASM) 107th Annual General Meeting in May 2007, suggesting oritavancin’s potential utility as a therapy for exposure to Bacillus anthracis, the bacterium that causes anthrax, having demonstrated efficacy in a mouse model both pre- and post-exposure to the bacterium^[5]

[edit] Clinical Progress

Results have been presented but not yet published from two pivotal Phase 3 clinical trials testing the efficacy of oritavancin for the treatment of complicated skin and skin-structure infections (cSSSI) caused by Gram-positive bacteria. The primary endpoints of both studies were successfully met, with oritavancin achieving efficacy with fewer days of therapy than the comparator agents (vancomycin followed by cephalexin). In addition, oritavancin showed a significantly improved safety profile with a 19.2 percent relative reduction in the overall incidence of adverse events versus vancomycin/cephalexin (p<0.001) in the second and larger pivotal trial^[6].

A Phase 2 clinical study is currently ongoing entitled “Single or Infrequent Doses for the Treatment of Complicated Skin and Skin Structure Infections (SIMPLIFI),” evaluating the efficacy and safety of either a single dose of oritavancin or an infrequent dose of oritavancin compared to the previously studied dosing regimen of 200mg oritavancin given once daily for 3 to 7 days^[7].

[edit] NDA Submission

On February 11, 2008, Targanta submitted a New Drug Application (NDA) to the US FDA seeking approval of oritavancin. ^[8]

[edit] References

v • d • e Antibacterials for systemic use: others (J01X) Glycopeptide Vancomycin (Oritavancin, Telavancin) - Teicoplanin (Dalbavancin) Polymyxins Colistin - Polymyxin B Steroid antibacterials Fusidic acid Imidazole derivatives Metronidazole - Tinidazole - Ornidazole Nitrofuran derivatives Nitrofurantoin - Nifurtoinol Other -mycin (Fosfomycin, Spectinomycin, Daptomycin, Hitachimycin) Xibornol - Clofoctol - Methenamine - Iclaprim - Mandelic acid - Nitroxoline - Linezolid