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Idenix Stock Plummets 47% on Negative HCV Drug Data

Staff Writer

Shares in Idenix Pharmaceuticals Inc. sank 47 percent as the FDA placed a clinical hold on studies of IDX184 and IDX320 for hepatitis C virus due to elevated liver enzymes in three healthy volunteers.

The safety-related hold comes as the Cambridge, Mass.-based company was seeking to partner lead HCV candidate IDX184, likely derailing any partnership plans.

News of the serious adverse events (SAEs) arising from the post-combinations study of IDX184 and IDX320 caused shares in Idenix (NASDAQ:IDIX) to tumble $2.81, closing at $3.18.

While investors seemed spooked by the news, some analysts indicated that the outlook for lead HCV candidate, IDX184, still looks hopeful. Remove the IDX320 compound from the equation, they say, and the data for IDX184 looks positive thus far.

Y. Katherine Xu, an analyst with Wedbush Securities Inc., told BioWorld Today that IDX184 is still "valuable" – with about 95 percent of the evidence stacked in its favor – and Oppenheimer & Co. analyst Brian Abrahams said in a research note that the compound "remains viable."

The elevated liver function tests were observed in three patients during the company's drug-to-drug interaction study of the IDX184 and IDX320 in healthy volunteers. Since then, the liver function tests have returned to nearly normal levels in all three subjects during follow-up.

But Idenix's efforts to find a partner for IDX184 likely have been pushed off course due to the liver toxicity signals in the drug-to-drug interaction study, according to Abrahams. "While we cannot rule it out, we believe 184 is less likely to have been responsible for the SAEs and that it remains viable, although this likely pushes back development/partnership timelines," he wrote.

The only negative data for IDX184 stems from the drug-to-drug interaction study, leading Xu to wonder whether the interaction with IDX320 may be to blame for the elevated liver enzymes.

In the Phase IIa study, patients in cohorts of 100-mg, 150-mg and 200-mg daily doses in combination with PegIFN/RBV achieved undetectable virus levels at 14 days. The side effect profile of that three-drug combination was consistent with the known side effect profile of PegIFN/RBV alone. The most common adverse events reported were fatigue, myalgia, headache and nausea.

When the hold was imposed, all planned studies of IDX184 and IDX320 to date already had been completed. And no healthy volunteers or patients are currently receiving IDX184 or IDX320. But due to the hold, no other studies of those HCV candidates can proceed.

IDX184, a liver-targeted HCV nucleotide prodrug, was in Phase IIa testing, while the IDX184/IDX320 combination was in Phase I.

Full data from studies of IDX184, IDX320 and IDX375 (a Phase I HCV non-nucleoside polymerase inhibitor) will be presented at the annual meeting of the American Association for the Study of Liver Diseases (AASLD) set for the end of October in Boston.

The likely delays from the clinical hold probably would be minimal for IDX184, Xu said. She had projected a launch in the first half of 2015, "which is pretty conservative, actually," Xu said, calling it a "well padded" launch date.

Her forecast of a $7 target valuation for Idenix also "is not going to change for now," Xu said, noting that her valuation methodology was based on IDXI84 and HIV candidate IDX899 as the key value drivers of the company. The combination of IDX320 and IDX184 didn't even factor into that model, she explained.

In the meantime, Idenix plans to submit full data to the FDA from the recently completed preclinical and clinical studies. Those studies include a three-month chronic toxicology study of IDX184 in combination with pegylated interferon/ribavirin (PegIFN/RBV); a three-day proof-of-concept study of IDX320 in hepatitis C (HCV) infected patients; and the IDX184 and IDX320 drug-drug interaction study in healthy volunteers.

Idenix's Jean-Pierre Sommadossi said, "We remain committed to the future potential of these drug candidates.

"We will work closely with independent experts and our external safety committee to better understand the cause of these serious adverse events in the combination study of IDX184 and IDX320, and to provide the FDA with more information in order to expedite their review and resolve this matter as quickly as possible," he added.

Currently, there are only three nucleoside polymerase inhibitors for HCV in development, including Idenix's IDXI84. The others that Abrahams is aware of are by Inhibitex Inc. (INX-189) and Pharmasset Inc. and Roche AG (RG7128). (See BioWorld Today, May 17, 2010.)

The scarcity of nucleoside polymerase inhibitors gives IDX184 value, Abrahams told BioWorld Today. He said he is not aware of any large pharmaceutical companies that have disclosed having such a compound. There are not yet any direct antiviral agents for HCV on the market. But both Vertex Pharmaceuticals Inc. and Merck & Co. Inc. have direct antivirals in Phase III, protease inhibitors telaprevir and boceprevir, respectively, which analysts view as approvable.

In October 2009, Swiss drugmaker Novartis AG waived its right to license IDX184, a nucleotide prodrug for HCV. As a result, Idenix retained worldwide rights to develop, commercialize and license IDX184.

As of its latest quarterly filing, the company had received $117.2 million of nonrefundable payments from Novartis that have been recorded as deferred revenue.

Published: September 8, 2010