Trade names Orbactiv ATC code J01XA05 (WHO) PubChem CID 16131319 Molar mass 1,793.1 g/mol | Routes of
administration Intravenous CAS Number 171099-57-3 ChemSpider 31149229 | |
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Lipoglycopeptide review dalbavancin and oritavancin
Oritavancin (INN, also known as LY333328, Orbactiv) is a novel semisynthetic glycopeptide antibiotic for the treatment of serious Gram-positive bacterial infections. Its chemical structure as a lipoglycopeptide is similar to vancomycin.
Contents
- Lipoglycopeptide review dalbavancin and oritavancin
- In vitro activity
- Mechanism
- Clinical trials
- History
- References
In August 2014, the United States FDA approved oritavancin for treatment of skin infections.
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. Oritavancin possesses potent and rapid bactericidal activity in vitro against a broad spectrum of both resistant and susceptible Gram-positive bacteria, including Staphylococcus aureus, MRSA, enterococci, and streptococci. Oritavancin was more active than either metronidazole or vancomycin against strains of Clostridium difficile tested.
Oritavancin has potential use as a therapy for exposure to Bacillus anthracis, the Gram-positive bacterium that causes anthrax, having demonstrated efficacy in a mouse model both before and after exposure to the bacterium.
Mechanism
The 4'-chlorobiphenylmethyl group disrupts the cell membrane of Gram-positive bacteria. It also acts by inhibition of transglycosylation and inhibition of transpeptidation.
Clinical trials
In 2003 results were presented from two pivotal phase-III clinical trials testing the efficacy of daily intravenous oritavancin for the treatment of acute bacterial skin and skin-structure infections (ABSSSI) caused by Gram-positive bacteria. The primary endpoints of both studies were met, with oritavancin achieving efficacy with fewer days of therapy than the comparator agents vancomycin followed by cephalexin. Oritavancin showed a statistically significant improved safety profile with a 19% relative reduction in the overall incidence of adverse events versus vancomycin/cephalexin in the second and larger pivotal trial.
History
Originally discovered and developed by Eli Lilly, oritavancin was acquired by InterMune in 2001 and then by Targanta Therapeutics in late 2005. In December 2008, the US Food and Drug Administration declined to approve oritavancin without additional studies, and an EU application was withdrawn.
In 2009, The Medicines Company acquired the development rights, completed clinical trials and submitted a new drug application to the FDA in February 2014. On August 6, 2014, the United States FDA approved oritavancin to treat skin infections.
A marketing authorisation valid throughout the European Union was granted on 19 March 2015 for the treatment of acute bacterial skin and skin structure infections in adults.