Two Hepatitis C Drug Candidates on Hold Because of Adverse Events

Robert Lowes

September 8, 2010 — The US Food and Drug Administration (FDA) has ordered drug maker Idenix to suspend development of 2 candidate drugs to treat hepatitis C virus after 3 individuals treated with a combination of these drugs in a clinical trial experienced liver function abnormalities, the company announced yesterday.

The 2 investigational drugs are a nucleoside polymerase inhibitor called IDX184 and a protease inhibitor called IDX320.

The FDA verbally notified Idenix on September 3 that the agency had placed IDX184 and IDX320 programs on clinical hold, pending a review of all clinical and preclinical data for the programs, according to the company. An Idenix press release quoted Chief Executive Officer and Chairman Jean-Pierre Sommadossi, PhD, as saying that the company had not yet received a formal letter from the FDA.

A clinical hold means that a study sponsor must delay a proposed investigation or suspend an ongoing one. When an ongoing study is on clinical hold, no new participants may be recruited or given an investigational medication, and patients already enrolled should stop receiving the treatment unless the FDA specifically authorizes it.

Idenix has completed its planned studies of IDX184 and IDX320, and no healthy trial participants or patients are receiving either experimental drug, the company stated.

In a 2-week phase 1 randomized, double-blind, placebo-controlled trial, 16 of 20 healthy individuals were randomly assigned to receive a combination of IDX184 and IDX320. Half of them received IDX184 plus placebo for the 2 full weeks and IDX320 just for the last week, and the other half received IDX320 for 2 weeks and IDX184 for the last week.

Although the drug duo was generally safe and tolerated, elevated liver function tests (LFTs) in 3 participants were deemed serious adverse events, according to Idenix, which reported these findings to the FDA. During follow-up, LFTs in these 3 participants returned to nearly normal.

In a conference call with stock analysts yesterday, Idenix Chief Medical Officer Douglas Mayers, MD, said that the 3 participants with elevated LFTs were later evaluated by liver specialists and screened for hepatitis, drugs and alcohol, and any potentially confounding medications. The elevated LFT in 1 patient, he said, appeared to be related to gallstones. No explanation has yet emerged for the adverse events experienced by the other 2 participants.

Idenix will investigate the adverse events and provide the FDA with the information it needs, said Dr. Sommadossi. "We remain committed to the future potential of these drug candidates."

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