icon-folder.gif   Conference Reports for NATAP  
  EASL 45th Annual Meeting
April 14-18, 2010
Vienna, Austria
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Idenix Pharmaceuticals Reports Favorable Pharmacokinetic Data for IDX320, a Potent, Multi-Genotypic Protease Inhibitor for the Treatment of Hepatitis C
  - IDX320 pharmacokinetic data in healthy volunteers suggest potential for once-daily dosing in HCV-infected patients
- Triple combinations of direct-acting antiviral agents demonstrate strong in vitro synergy against hepatitis C virus (HCV)
- Data were presented in three posters at the 45th Annual Meeting of the European Association for the Study of the Liver (EASL)
press announcement
CAMBRIDGE, Mass., April 16 /PRNewswire-FirstCall/ -- Idenix Pharmaceuticals, Inc. (Nasdaq: IDX) a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases, today reported promising in vitro data for IDX320, an HCV protease inhibitor, demonstrating potent and selective antiviral activity in multiple genotypes, or strains, of the virus. The favorable pharmacokinetic profile defined in preclinical studies was confirmed by interim Phase I clinical data in healthy volunteers. Additional data presented demonstrated that a combination of three Idenix drug candidates, including IDX320, with different mechanisms of action produced strong synergy in vitro.These data support the evaluation of direct-acting antiviral (DAA) combination regimens for the treatment of HCV.
"We are excited about the preclinical and first-in-man data presented today from the IDX320 program. With the in vitropotency and favorable pharmacokinetic profile seen to date combined with the potential for once-daily dosing and multi-genotypic coverage, we believe IDX320 could offer improvements over other protease inhibitors currently in development," said David Standring, Ph.D., Idenix's executive vice president, biology. "The Phase I single and multiple ascending dose clinical study in healthy volunteers is now complete, and we look forward to advancing IDX320 into a three-day proof-of-concept study expected to begin in the second quarter."
"The in vitro combination data presented today continue to support our belief that the future of HCV treatment will be a combination of direct-acting antivirals from different drug classes. We are pursuing a drug development strategy to achieve that goal," said Jean-Pierre Sommadossi, Ph.D., chief executive officer of Idenix.
IDX320 is a potent inhibitor of NS3/4A proteases from genotypes 1a, 1b, 2a and 4a (IC(50) values from 0.8 to 1.9 nM), as well as from genotype 3a (IC(50)=23 nM). IDX320 did not inhibit nine tested cellular proteases (IC(50) > 10 micromolars) in vitro, suggesting high selectivity. IDX320 bound tightly to the HCV protease enzyme with a long dis sociation half-life (> 9 hours). The signature mutation observed& nbsp;in vitro was D168V, consistent with other macrocyclic inhibitors. This mutation had reduced replication fitness and was susceptible to treatment with interferon as well as other classes of DAAs. Additionally, IDX320 retained activity against mutations that produce resistance to other protease inhibitors in clinical development.(Lallos, et al, "In Vitro Antiviral Activity of IDX320, a Novel and Potent Macrocyclic HCV Protease Inhibitor", Poster #768.)
After single 2 mg/kg oral doses of IDX320 in two animal species, favorable bioavailability and a long plasma half-life were observed, with substantial plasma concentrations 24 hours post dose. These preclinical data were confirmed in orally-dosed healthy volunteers (n=6) receiving a single 200 mg tablet. Further, no sig nificant in vitro inhibition of human drug metabolizing enzymes, CYP450s and UGT1A1, by IDX320 suggests low potential for drug-drug interactions in patients. (Good, et al, "Preclinical Pharmacokinetic Profile of IDX320, a Novel and Potent HCV Protease Inhibitor", Poster #750).
Double and triple combination in vitro studies of Idenix's HCV direct-acting antiviral drug candidates from different HCV drug classes, including IDX184 (a nucleotide inhibitor), IDX320 (a protease inhibitor), IDX375 (a non-nucleoside inhibitor) and a prototype Idenix NS5A inhibitor, were reported. Data demonstrated that double combinations (IDX320 with IDX184, IDX375 or NS5A inhibitor) resulted in additive to mildly synergistic effects after 3 days of treatment in vitro. Furthermore, triple combinations, especially those inc luding agents from three different HCV drug classes (IDX184/IDX320/IDX375 or IDX184/IDX320/NS5A inhibitor), demonstrated the strongest synergy in vitro. Similar results were observed over 14-days of treatment with no evidence of viral breakthrough or cellular cytotoxicity. (La Colla, et al, "A Triple Combination of Direct-Acting Antiviral Agents Demonstrates Robust Anti-HCV Activity In Vitro", Poster #769.)
About HCV
Hepatitis C virus is a common blood-borne pathogen infecting three to four million people worldwide annually. Currently, an estimated 170 million people are infect ed worldwide, representing a nearly 5-fold greater prevalence than human immunodeficiency virus.(1)
About Idenix
Idenix Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts, is a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases. Idenix's current focus is on the treatment of infections caused by hepatitis C virus. For further information about Idenix, please refer to www.idenix.com. (1.) Lavanchy (2009) Liver International. 29(s1):74-81.
Idenix Pharmaceuticals Contact:
Teri Dahlman: 617-995-9905 SOURCE Idenix Pharmaceuticals, Inc