Three companies developing direct-acting antiviral agents (DAAs) for hepatitis C virus (HCV) infection recently announced progress on new experimental drug candidates. Achillion HCV Protease Inhibitors On January 9 Achillion Pharmaceuticals announced results from clinical trials of its investigational HCV protease inhibitors, including:
Interim Phase 2 data from a study of ACH-1625 in treatment-naive genotype 1 chronic hepatitis C patients;
Exploratory data from a trial of ACH-1625 for genotype 3 patients;
Initial proof-of-concept data from an early study of ACH-2684.
"ACH-1625 is emerging as a fascinating and potentially superior, once-daily protease inhibitor that competes well against all other DAAs in development, regardless of their mechanism, based upon ACH-1625's safety, efficacy, genotypic coverage and emerging resistance mutation profile," stated Achillion President and CEO Michael Kishbauch. "Further, ACH-2684 shows preliminary promise in its ability to treat HCV, with a safety profile that looks very good, and over the next few months we will expand our clinical experience to define the dose response for its use across all HCV genotypes."
Presidio NS5A Inhibitor The same day, Presidio Pharmaceuticals announced the successful completion of a Phase 1a dose-ranging study of its second-generation HCV NS5A inhibitor PPI-668 in healthy volunteers. The drug will now advance to a Phase 1b trial of dose-related efficacy.
The randomized Phase 1a dose-ranging study, which included 32 healthy volunteers in New Zealand, found that all PPI-668 dose regimens tested were well-tolerated with no serious clinical adverse events.
“These first clinical data for PPI-668 indicate excellent tolerance in healthy subjects for up to five days,” said Presidio Chief Medical Officer Nathaniel Brown. “Equally important, the pharmacokinetic profile of PPI-668 is very encouraging, suggesting that effective plasma concentrations can be obtained with relatively low, once-daily doses of PPI-668 -- which will facilitate co-formulation of PPI-668 with other HCV antivirals in future combination therapies for hepatitis C.”
The company also announced that it has discovered a lead chemical series of non-nucleoside HCV NS5B polymerase inhibitors with potent activity against all major HCV genotypes. Presidio hopes to develop 2 complementary antivirals that can be used together in combination regimens.
Idenix Development Pipeline Finally, Idenix Pharmaceuticals reported that it has started a Phase 1 study of an NS5A inhibitor, IDX719, that has shown activity against multiple HCV genotypes. The first part of the study will assess safety and pharmacokinetics in healthy volunteers, followed by a 3-day evaluation of the drug in treatment-naive genotype 1 patients.
The company has also selected a pair of next-generation nucleotide HCV polymerase inhibitors, IDX19368 and IDX19370, which it plans to test in clinical studies.
"Over the past year, Idenix has made significant progress in both our core nucleotide and NS5A programs," stated Idenix President and CEO Ron Renaud. "The preclinical profile of IDX719 is very competitive, and we are leveraging the company's significant nucleotide chemistry expertise to discover novel nucleotides with promising properties as well as continuing to strengthen our IP position. We are excited about the potential of our novel antiviral compounds in the evolving HCV field in the coming year."
1/17/12 Sources
Achillion Pharmaceuticals. Achillion Reports Clinical Data on Portfolio of Protease Inhibitors. Press release. January 9, 2012.
Presidio Pharmaceuticals. Presidio Pharmaceuticals Reports Progress with Hepatitis C Antiviral Programs. Press release. January 9, 2012.
Idenix Pharmaceuticals. Idenix Reports Advancement of HCV Development Pipeline. Press release. January 9, 2012.
