Pre-clinical Model Predictions Made by ICPD are Validated in Infected Patients

Albany, NY, November 12, 2008 – Earlier pre-clinical model predictions for oritavancin made by the Institute for Clinical Pharmacodynamics (ICPD) scientists in collaboration with scientists from Targanta Therapeutics Corporation have been validated in infected patients with complicated skin and skin structure infections.

Oritavancin is a new lipoglycopeptide antibiotic in late-stage clinical development (Targanta Therapeutics Corporation) with potent activity against Gram-positive pathogens, including MRSA. As previously announced in April 2008, ICPD’s Co-Director, Dr. Sujata Bhavnani, presented a platform presentation as part of the 2008 European Society of Clinical Microbiology and Infectious Diseases (ESCMID) conference in Barcelona, Spain, which described the use of pharmacokinetic-pharmacodynamic principles to provide a basis for optimizing single and infrequent multiple oritavancin dosing regimens. The analysis utilized oritavancin exposure data in humans derived from previous clinical studies and animal infection models in which oritavancin was dosed in a manner that resulted in exposures that mimicked those achieved in humans. ICPD’s Director, Dr. Paul G. Ambrose, commented, “The analysis demonstrated the potential benefit of front-loaded dosing strategies. After analyzing the animal models, ICPD predicted that the most front-loaded regimen would be the best course of action.” Dr. Ambrose further explained, “Front-loading the exposure results in a more rapid and complete bacterial kill and extending the therapy duration increases the exposure intensity required to effect bacterial eradication. Having the highest exposure at the time of greatest bacterial count results in the greatest kill possible and optimizes the likelihood of positive clinical outcome. This, in turn, reduces the likelihood of spontaneous mutation, and should eliminate a pre-existing resistant subpopulation.”

As a result of these analyses, Targanta Therapeutics Corporation launched a three-arm Phase 2 clinical trial comparing two short and intensive oritavancin dosing regimens with the previously-studied oritavancin regimen for the treatment of patients with complicated skin and skin structure infections. In the trial, patients were randomized to one of three treatment arms for which patients received either: 200 mg of oritavancin intravenous (IV) daily for a minimum of three days and up to a maximum of seven days, or a single dose of 1200 mg of oritavancin IV, or a single dose of 800 mg of oritavancin IV, with an optional second dose of 400 mg IV given on Day 5 at investigator discretion. Initial efficacy and safety results from the trial that was based upon the ICDP analyses and predictions have recently been announced by Targanta Therapeutics Corporation.

Dr. Ambrose presented the results from this Phase 2 study at the 2008 joint meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) and the Infectious Disease Society of America (IDSA) in Washington DC. “The problems of drug resistance continue to grow,” noted Dr. Ambrose. “We are very pleased that ICPD’s earlier pre-clinical model predictions for oritavancin have been validated and look forward to contributing to other drug development programs with the common goal of accelerating the availability of drugs that will enhance patient outcomes.”

About ICPD

The ICPD serves as a center for translational science collaboration to the world. We help pharmaceutical and biotechnology companies develop more effective and safer drugs through advanced methods of pharmacokinetic and pharmacodynamic system analysis. Our general contact information is as follows:

Telephone: (518) 429-2600
Info@ICPD.com