US FDA removes partial clinical hold on Idenix HCV candidate
This article was originally published in Scrip
Idenix Pharmaceuticals has been notified by the US FDA that the partial clinical hold on its hepatitis C virus treatment candidate IDX184 has been lifted and that it can continue with a Phase IIb trial evaluating the product, the company said.
It said to Scrip, "We now have several options regarding future studies with IDX184 with the primary goal to evaluate interferon-free regimens as quickly as possible. We will be in a position to give more details about future studies in the coming months."
IDX184 is Idenix's lead product candidate for the treatment of hepatitis C virus (HCV) infection and is a pan-genotypic oral nucleotide polymerase inhibitor. The 12-week, Phase IIb study, which was initiated in July 2011 (scripintelligence.com, 18 November 2011) is evaluating IDX184 in combination with pegylated interferon and ribavirin (PegIFN/RBV).
The partial hold originated from a full clinical hold placed by the FDA in September 2010 on IDX184 and another of Idenix's HCV candidates, IDX320, a protease inhibitor. The hold was put into force due to three cases of elevated liver enzyme levels in a Phase I drug-interaction study in healthy volunteers (scripintelligence.com, 8 September 2010).
After the company was able to establish that the observed toxicity was likely caused by IDX320, the FDA, in the following February, removed the full clinical hold on IDX184 permitting Idenix to move ahead with its Phase IIb trial. However, a partial hold still remained in place (scripintelligence.com, 11 February 2011).
Accordingly, Idenix initiated enrolment of treatment-naive genotype 1 HCV-infected patients into the randomised, double-blind, parallel group Phase IIb trial in July 2011. The study, which was expected to include 100 patients, had two treatment arms, either 50mg or 100mg of IDX184 administered once-daily for 12 weeks - each arm in combination with PegIFN/RBV. Study objectives included safety and tolerability, and antiviral activity endpoints.
The company had previously said it planned to release interim one-month safety and antiviral activity data for the first 30 patients in the first quarter of 2012 and in its latest announcement, said: "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."
Additionally, Idenix said there had been a change to the trial's protocol: "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 enrolment criteria."
Idenix told Scrip, "The removal of the partial clinical hold allows us to expand the Phase IIb program 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. We will submit data from the ongoing Phase IIb study to EASL, an upcoming scientific meeting in Europe in April." It added that it was too early to discuss the timing of marketing applications for IDX184.
The company was keen to note that 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 maximising drug efficacy and limiting systemic side effects with low, once-daily dosing.
"We have multiple ongoing discussions with potential partners. We believe we have several strategic approaches open to us for IDX184, including a potential collaboration or partnership, and have the financial flexibility to select the best option for creating shareholder value. We will be able to consider various deal structures to determine which one we would consider most beneficial for IDX184, for Idenix and our shareholders. Our main focus is to put IDX184 in a situation where it has the best chance to succeed," Idenix commented.