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{{drugbox |
{{drugbox |
| IUPAC_name = (4''R)-22-O-(3-Amino-2,3,6-trideoxy-3-C-methyl-alpha-L-arabinohexopyranosyl)-N3''-(p-(p-chlorophenyl)benzyl)vancomycin
| IUPAC_name = (4''R'')-22-O-(3-Amino-2,3,6-trideoxy-3-C-methyl-alpha-L-arabinohexopyranosyl)-N3-(p-(p-chlorophenyl)benzyl)vancomycin
| image = Oritavancin.svg
| image = Oritavancin.svg
| CAS_number = 171099-57-3
| CAS_number = 171099-57-3
| ATC_prefix =
| ATC_prefix = none
| ATC_suffix =
| ATC_suffix =
| PubChem = 16131319
| PubChem = 16131319
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'''Oritavancin''' ([[International Nonproprietary Name|INN]], also known as '''LY333328''') is a novel semi-synthetic [[Glycopeptide antibiotic|glycopeptide antibiotic]] being developed for the treatment of serious [[Gram-positive|Gram-positive]] infections. Originally discovered and developed by [[Eli Lilly and Company|Eli Lilly]], oritavancin was acquired by InterMune in 2001 and then by [[Targanta Therapeutics Corporation|Targanta Therapeutics]] in late 2005.<ref>[http://www.bioworld.com/servlet/com.accumedia.web.Dispatcher?next=bioWorldHeadlines_article&forceid=46239 Targanta Revives Oritavancin: Next Weapon Against cSSSI? BioWorld Today, November 26, 2007]</ref>
'''Oritavancin''' ([[International Nonproprietary Name|INN]], also known as '''LY333328''') is a novel semi-synthetic [[Glycopeptide antibiotic|glycopeptide antibiotic]] being developed for the treatment of serious [[Gram-positive|Gram-positive]] infections. Originally discovered and developed by [[Eli Lilly and Company|Eli Lilly]], oritavancin was acquired by InterMune in 2001 and then by [[Targanta Therapeutics Corporation|Targanta Therapeutics]] in late 2005.<ref>[http://www.bioworld.com/servlet/com.accumedia.web.Dispatcher?next=bioWorldHeadlines_article&forceid=46239 Targanta Revives Oritavancin: Next Weapon Against cSSSI? BioWorld Today, November 26, 2007]</ref>


===''In Vitro'' Activity===
===''In vitro'' activity===


Oritavancin shares certain properties with other members of the glycopeptide class of antibiotics, which includes [[Vancomycin|vancomycin]], the current standard of care for serious Gram-positive infections in the United States and Europe<ref>{{cite journal |author=Scheinfeld, N |title=A comparison of available and investigational antibiotics for complicated skin infections and treatment-resistant ''Staphylococcus aureus'' and ''enterococcus'' |journal= J Drugs Dermatol. |volume=6 |issue=4 |pages=97&ndash;103 |year=2007 |pmid=17373167}}</ref>. 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]]<ref>2007 ICAAC Posters: E-1612 “''In Vitro'' Activity Profile of Oritavancin against a Broad Spectrum of Aerobic and Anaerobic Bacterial Pathogens”/E -1613 “''In Vitro'' Activity Profile of Oritavancin (ORI) Against Organisms Demonstrating Key Resistance Profiles to Other Antimicrobial Agents”/E-1614 “''In vitro'' Time Kill Studies of Oritavancin against Drug-resistant Isolates of ''Staphylococcus aureus'' and ''Enterococci''”/E-1615 “Anti-Enterococcal Activity Profile of Oritavancin, a Potent Lipoglycopeptide under Development for Use Against Gram-Positive Infections”/E-1616 “Anti-Streptococcal Activity Profile of Oritavancin, a Potent Lipoglycopeptide under Development for Use Against Gram-Positive Infections”/E-1617 “''In Vitro'' Activity Profile of Oritavancin (ORI) Against Resistant Staphylococcal Populations From a Recent Surveillance Initiative”/E-1620 “Pharmacokinetic Concentrations of Oritavancin Kill Stationary-Phase and Biofilm ''Staphylococcus aureus'' ''In Vitro''.” / [http://media.integratir.com/targ/PressReleases/TARG%20ICAAC%20In%20Vitro%20091907.pdf Targanta Press Release September 19, 2007]</ref>. Two posters presented at the meeting also demonstrated that oritavancin was more active than either metronidazole or vancomycin against strains of [[Clostridium difficile]] tested<ref>ICAAC 2007 Posters: “''In Vitro'' Susceptibility of Genotypically Distinct ''Clostridium difficile'' Strains to Oritavancin” and “Activity of Metronidazole, Vancomycin and Oritavancin Against Epidemic ''Clostridium difficile'' Spores” / [http://media.integratir.com/targ/PressReleases/TARG%20ICAAC%20C%20Diff%20091907.pdf Targanta Press Release September 19, 2007]</ref>. In addition, research was conducted in partnership with the [[United States Army Medical Research Institute of Infectious Diseases|U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID)]] and presented at the [[American Society for Microbiology|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|anthrax]], having demonstrated efficacy in a mouse model both pre- and post-exposure to the bacterium<ref>ASM 2007 Poster: “Efficacy of Oritavancin in a Murine Model of ''Bacillus anthracis'' Spore Inhalation Anthrax” / [http://media.integratir.com/targ/PressReleases/TARG%20Mouse%20Anthrax%20052407.pdf Targanta Press Release May 24, 2007]</ref>
Oritavancin shares certain properties with other members of the glycopeptide class of antibiotics, which includes [[Vancomycin|vancomycin]], the current standard of care for serious Gram-positive infections in the United States and Europe<ref>{{cite journal |author=Scheinfeld, N |title=A comparison of available and investigational antibiotics for complicated skin infections and treatment-resistant ''Staphylococcus aureus'' and ''enterococcus'' |journal= J Drugs Dermatol. |volume=6 |issue=4 |pages=97&ndash;103 |year=2007 |pmid=17373167}}</ref>. 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]]<ref>2007 ICAAC Posters: E-1612 “''In Vitro'' Activity Profile of Oritavancin against a Broad Spectrum of Aerobic and Anaerobic Bacterial Pathogens”/E -1613 “''In Vitro'' Activity Profile of Oritavancin (ORI) Against Organisms Demonstrating Key Resistance Profiles to Other Antimicrobial Agents”/E-1614 “''In vitro'' Time Kill Studies of Oritavancin against Drug-resistant Isolates of ''Staphylococcus aureus'' and ''Enterococci''”/E-1615 “Anti-Enterococcal Activity Profile of Oritavancin, a Potent Lipoglycopeptide under Development for Use Against Gram-Positive Infections”/E-1616 “Anti-Streptococcal Activity Profile of Oritavancin, a Potent Lipoglycopeptide under Development for Use Against Gram-Positive Infections”/E-1617 “''In Vitro'' Activity Profile of Oritavancin (ORI) Against Resistant Staphylococcal Populations From a Recent Surveillance Initiative”/E-1620 “Pharmacokinetic Concentrations of Oritavancin Kill Stationary-Phase and Biofilm ''Staphylococcus aureus'' ''In Vitro''.” / [http://media.integratir.com/targ/PressReleases/TARG%20ICAAC%20In%20Vitro%20091907.pdf Targanta Press Release September 19, 2007]</ref>. Two posters presented at the meeting also demonstrated that oritavancin was more active than either metronidazole or vancomycin against strains of [[Clostridium difficile]] tested<ref>ICAAC 2007 Posters: “''In Vitro'' Susceptibility of Genotypically Distinct ''Clostridium difficile'' Strains to Oritavancin” and “Activity of Metronidazole, Vancomycin and Oritavancin Against Epidemic ''Clostridium difficile'' Spores” / [http://media.integratir.com/targ/PressReleases/TARG%20ICAAC%20C%20Diff%20091907.pdf Targanta Press Release September 19, 2007]</ref>. In addition, research was conducted in partnership with the [[United States Army Medical Research Institute of Infectious Diseases|U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID)]] and presented at the [[American Society for Microbiology|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|anthrax]], having demonstrated efficacy in a mouse model both pre- and post-exposure to the bacterium<ref>ASM 2007 Poster: “Efficacy of Oritavancin in a Murine Model of ''Bacillus anthracis'' Spore Inhalation Anthrax” / [http://media.integratir.com/targ/PressReleases/TARG%20Mouse%20Anthrax%20052407.pdf Targanta Press Release May 24, 2007]</ref>


===Clinical Progress===
===Clinical progress===


Results have been presented (in 2003) but possibly not yet published from two pivotal Phase 3 clinical trials testing the efficacy of daily intravenous 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<ref>ICAAC 2003 Late-breaker poster: "Phase III Trial Comparing 3-7 days of Oritavancin vs. 10-14 days of Vancomycin/Cephalexin in the Treatment of Patients with Complicated Skin and Skin Structure Infections (cSSSI)" / [http://phx.corporate-ir.net/phoenix.zhtml?c=100067&p=irol-newsArticle&ID=448643&highlight= InterMune Press Release September 15, 2003]</ref>.
Results have been presented (in 2003) but possibly not yet published from two pivotal Phase 3 clinical trials testing the efficacy of daily intravenous 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<ref>ICAAC 2003 Late-breaker poster: "Phase III Trial Comparing 3-7 days of Oritavancin vs. 10-14 days of Vancomycin/Cephalexin in the Treatment of Patients with Complicated Skin and Skin Structure Infections (cSSSI)" / [http://phx.corporate-ir.net/phoenix.zhtml?c=100067&p=irol-newsArticle&ID=448643&highlight= InterMune Press Release September 15, 2003]</ref>.
Line 36: Line 36:
A Phase 2 clinical study was planned to run until May 2008 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<ref>[http://www.clinicaltrials.gov/ct2/show/NCT00514527?term=oritavancin&rank=1 ClinicalTrials.gov NCT00514527]</ref>.
A Phase 2 clinical study was planned to run until May 2008 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<ref>[http://www.clinicaltrials.gov/ct2/show/NCT00514527?term=oritavancin&rank=1 ClinicalTrials.gov NCT00514527]</ref>.


===Regulatory Submissions===
===Regulatory submissions===
On February 11, 2008, Targanta submitted a [[New Drug Application]] (NDA) to the [[United States|US]] [[Food and Drug Administration|FDA]] seeking approval of oritavancin;<ref>{{cite web |url=http://www.drugs.com/nda/oritavancin_080211.html |title=Drugs.com, Targanta Submits Oritavancin New Drug Application |accessdate=2008-02-12 |format= |work= }}</ref> in April 2008, the FDA accepted the NDA submission for standard review, establishing an action date of December 8, 2008.<ref>{{cite web |url=http://www.fdanews.com/newsletter/article?articleId=105717&issueId=11481 |title=FDA News, Targanta to Get FDA Decision by December |accessdate=2008-04-10 |format= |work= }}</ref>
On February 11, 2008, Targanta submitted a [[New Drug Application]] (NDA) to the [[United States|US]] [[Food and Drug Administration|FDA]] seeking approval of oritavancin;<ref>{{cite web |url=http://www.drugs.com/nda/oritavancin_080211.html |title=Drugs.com, Targanta Submits Oritavancin New Drug Application |accessdate=2008-02-12 |format= |work= }}</ref> in April 2008, the FDA accepted the NDA submission for standard review, establishing an action date of December 8, 2008.<ref>{{cite web |url=http://www.fdanews.com/newsletter/article?articleId=105717&issueId=11481 |title=FDA News, Targanta to Get FDA Decision by December |accessdate=2008-04-10 |format= |work= }}</ref>


Revision as of 11:29, 31 July 2009

Oritavancin
Clinical data
Routes of
administration		intravenous
ATC code
  • none
Identifiers
  • (4R)-22-O-(3-Amino-2,3,6-trideoxy-3-C-methyl-alpha-L-arabinohexopyranosyl)-N3-(p-(p-chlorophenyl)benzyl)vancomycin
CAS Number
PubChem CID
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC86H97Cl3N10O26
Molar mass1793.1 g/mol g·mol−1

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]

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]

Clinical progress

Results have been presented (in 2003) but possibly not yet published from two pivotal Phase 3 clinical trials testing the efficacy of daily intravenous 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 was planned to run until May 2008 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].

Regulatory submissions

On February 11, 2008, Targanta submitted a New Drug Application (NDA) to the US FDA seeking approval of oritavancin;[8] in April 2008, the FDA accepted the NDA submission for standard review, establishing an action date of December 8, 2008.[9]

9 Dec 2008 the FDA said insufficient data for approval of oritavancin had been provided.[10]

Additionally, Targanta’s Marketing Authorization Application (MAA) for oritavancin was submitted and accepted for review by the European Medicines Agency (EMEA) in June 2008.[11]

References

  1. ^ Targanta Revives Oritavancin: Next Weapon Against cSSSI? BioWorld Today, November 26, 2007
  2. ^ Scheinfeld, N (2007). "A comparison of available and investigational antibiotics for complicated skin infections and treatment-resistant Staphylococcus aureus and enterococcus". J Drugs Dermatol. 6 (4): 97–103. PMID 17373167.
  3. ^ 2007 ICAAC Posters: E-1612 “In Vitro Activity Profile of Oritavancin against a Broad Spectrum of Aerobic and Anaerobic Bacterial Pathogens”/E -1613 “In Vitro Activity Profile of Oritavancin (ORI) Against Organisms Demonstrating Key Resistance Profiles to Other Antimicrobial Agents”/E-1614 “In vitro Time Kill Studies of Oritavancin against Drug-resistant Isolates of Staphylococcus aureus and Enterococci”/E-1615 “Anti-Enterococcal Activity Profile of Oritavancin, a Potent Lipoglycopeptide under Development for Use Against Gram-Positive Infections”/E-1616 “Anti-Streptococcal Activity Profile of Oritavancin, a Potent Lipoglycopeptide under Development for Use Against Gram-Positive Infections”/E-1617 “In Vitro Activity Profile of Oritavancin (ORI) Against Resistant Staphylococcal Populations From a Recent Surveillance Initiative”/E-1620 “Pharmacokinetic Concentrations of Oritavancin Kill Stationary-Phase and Biofilm Staphylococcus aureus In Vitro.” / Targanta Press Release September 19, 2007
  4. ^ ICAAC 2007 Posters: “In Vitro Susceptibility of Genotypically Distinct Clostridium difficile Strains to Oritavancin” and “Activity of Metronidazole, Vancomycin and Oritavancin Against Epidemic Clostridium difficile Spores” / Targanta Press Release September 19, 2007
  5. ^ ASM 2007 Poster: “Efficacy of Oritavancin in a Murine Model of Bacillus anthracis Spore Inhalation Anthrax” / Targanta Press Release May 24, 2007
  6. ^ ICAAC 2003 Late-breaker poster: "Phase III Trial Comparing 3-7 days of Oritavancin vs. 10-14 days of Vancomycin/Cephalexin in the Treatment of Patients with Complicated Skin and Skin Structure Infections (cSSSI)" / InterMune Press Release September 15, 2003
  7. ^ ClinicalTrials.gov NCT00514527
  8. ^ "Drugs.com, Targanta Submits Oritavancin New Drug Application". Retrieved 2008-02-12.
  9. ^ "FDA News, Targanta to Get FDA Decision by December". Retrieved 2008-04-10.
  10. ^ http://www.fiercebiotech.com/press-releases/fda-issues-complete-response-letter-oritavancin
  11. ^ "Pharmaceutical Business Review, EMEA accepts Targanta's oritavancin MAA for review". Retrieved 2008-06-26.
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