Idenix Pharmaceuticals has announced that it has received verbal notice from the FDA ( Food and Drug Administration ) that a partial clinical hold has been placed on IDX184, a nucleotide polymerase inhibitor under development for the treatment of hepatitis C virus ( HCV ).

As a result of the recent occurrence of a serious cardiac-related adverse event encountered with a competitor's nucleotide polymerase inhibitor for the treatment of HCV, the FDA has expressed an interest in further reviewing the safety of IDX184 and has placed IDX184 on partial clinical hold. In previous clinical trials as well as the ongoing phase IIb clinical trial of IDX184 in combination with Pegylated interferon and Ribavirin ( PegIFN/RBV ), there has been no evidence to date of cardiotoxicity in patients dosed with IDX184 with PegIFN/RBV beyond that seen with PegIFN/RBV alone. There are currently no patients receiving IDX184 worldwide.

The FDA has requested additional data on patients treated with IDX184.

IDX184 is an unpartnered, novel, liver-targeted nucleotide prodrug of 2'-methyl guanosine, which includes liver-targeting technology. This technology enables the delivery of nucleoside monophosphate to the liver, leading to the formation of high levels of nucleoside triphosphate, potentially maximizing drug efficacy and limiting systemic side effects with low, once-daily dosing.

Idenix Pharmaceuticals has reported interim data in June 2012 for the first cohort of 31 patients from an ongoing phase IIb clinical trial of IDX184 in combination with PegInterferon and Ribavirin. Of the patients who achieved an extended rapid virologic response ( undetectable levels of virus at 4 weeks and 12 weeks ) and completed an additional 12 weeks of PegIFN/RBV ( n=9 ), 100% of patients ( 4/4 ) in the 100 mg arm and 80% of patients ( 4/5 ) in the 50 mg arm achieved a sustained virologic response four weeks after the completion of treatment ( SVR4 ).

In July 2012, an independent data safety monitoring board reviewed the safety data for this study and confirmed that the side effect profile of IDX184 combined with PegIFN/RBV is consistent with that of PegInterferon and Ribavirin alone. ( Xagena )

Source: Idenix Pharmaceuticals, 2012

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