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Setbacks for Hepatitis C Drugs in Clinical Trials

September 1, 2012


On August 1, 2012, New York-based Bristol-Myers Squibb Company reported that it discontinued development of the experimental hepatitis C drug BMS-986094 (formerly INX-189), after the death of a patient from heart failure. The patient had been taking BMS-986094, part of a class of hepatitis C drugs known as nucleotide polymerase inhibitors, in a phase III clinical trial. The company also reported that eight other patients experienced serious complications such as heart and kidney toxicity. Bristol-Myers Squibb is working closely with the US Food and Drug Administration (FDA) and clinical study investigators, monitoring patients and conducting studies to evaluate the potential mechanism of toxicity.


Later in August, the FDA placed a partial hold on a similar hepatitis C drug, a nucleotide polymerase inhibitor called IDX184. The drug is being developed by Idenix Pharmaceuticals, based in Cambridge, MA, which produces drugs to treat human viral diseases. Although the FDA reported no heart-related side effects linked directly to the drug, some heart side effects have been seen in patients treated with IDX184 in combination with standard hepatitis drugs.

In 2010 the FDA placed a clinical hold on trials of IDX184 over concerns about its effects on the liver. It removed the hold in February 2012. Idenix recently completed a mid-stage clinical trial of IDX184 and is preparing to report results.


At the end of August, the FDA placed a clinical hold on Idenix’s IDX19368 over the potential for cardiac-related side effects similar to those in Bristol-Myers Squibb’s BMS-986094. IDX19368 is a next-generation nucleotide polymerase inhibitor being developed to treat hepatitis C. The FDA is requiring additional cardiac testing of all patients enrolled in clinical trials of the drug. Data from the echocardiograms will be submitted to the FDA for review.

"Based on our discussions with the FDA, we understand the clinical hold is a precautionary decision made by the FDA in light of the adverse events seen with BMS-986094," said Ron Renaud, Idenix President and CEO. "Both IDX184 and IDX19368 fall into the same broader class of NS5B inhibitors, and share the same active metabolite as BMS-986094. However, there are many attributes of our compounds, particularly the prodrug approach, that we believe favorably differentiate the toxicity profiles from that of BMS-986094. We recently learned that Bristol-Myers Squibb has agreed to share relevant information on BMS-986094 with us and hope this helps us to resolve this issue quickly."

Sources: The Associated Press, August 16; Bloomberg Businessweek, August 24, 2012; Idenix news release dated August 27, 2012