Idenix Pharmaceuticals Inc., a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases, has received notification from the US Food and Drug Administration (FDA) that the partial clinical hold on IDX184 has been removed and that the company's 12-week phase II b study evaluating IDX184 in combination with pegylated interferon and ribavirin (PegIFN/RBV) may continue.
IDX184, the company's lead product candidate for the treatment of hepatitis C virus (HCV) infection is a pan-genotypic oral nucleotide polymerase inhibitor, and has demonstrated a high barrier to resistance in vitro and potent antiviral activity in both preclinical and clinical studies. Recently announced interim phase IIb data demonstrated favourable antiviral activity and no serious adverse events.
“After review of the interim safety and antiviral activity results from the IDX184 phase II b clinical trial, the FDA removed the partial clinical hold and has allowed us to continue enrollment of this study,” Ron Renaud, president and chief executive officer of Idenix, commented. “Importantly, this allows us to expand the phase IIb programme and evaluate IDX184 in interferon-free combination regimens with other direct-acting antivirals. We are working toward beginning all-oral combination trials as quickly as possible.”
In July 2011, Idenix initiated enrollment of treatment-naive genotype 1 HCV-infected patients into a randomized, double-blind, parallel group phase IIb clinical trial of IDX184. The study features two treatment arms, either 50 mg or 100 mg of IDX184 administered once-daily for 12 weeks, each arm in combination with PegIFN/RBV. Study objectives include safety and tolerability, and antiviral activity endpoints. The FDA has agreed to truncate the study from 100 patients, as in the original protocol, to a total of 60 patients, and to expand the enrollment criteria.
A clinical hold originally was issued in September 2010 as a result of three cases of elevated liver function tests observed during a drug-drug interaction study in healthy volunteers of the combination of IDX184 and IDX320, an investigational HCV protease inhibitor. Idenix reviewed available data and conducted additional preclinical studies. With the help of independent experts and an external safety committee, the Company concluded that the observed toxicity was likely caused by IDX320 and submitted all data to the FDA. At the beginning of 2011, the FDA removed a full clinical hold on IDX184, and the program was placed on partial clinical hold allowing the Company to initiate the 12-week phase IIb study for IDX184 in July 2011. In January 2012, Idenix submitted interim phase IIb data for the first 31 patients to the FDA, along with a recommendation from the independent Data Safety Monitoring Board to continue the study, and requested removal of the partial clinical hold on IDX184. The partial clinical hold has now been removed allowing the initiation of dosing of an additional 30 patients in the ongoing phase IIb clinical trial and the initiation of a broad phase IIb programme with IDX184 in the coming months.
IDX184 is an unpartnered, novel, liver-targeted nucleotide prodrug of 2'-methyl guanosine, which includes Idenix's proprietary 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.