Excerpt:
IDX-184 has had no safety issues to date. Nonetheless, structural similarities between Idenix's IDX-184 and Bristol-Myers Squibb's (BMY) BMS-094 were sufficient to warrant concern. Clinical development of the latter drug, which Bristol-Myers acquired in the $2.5 billion takeover of Inhibitex, has been discontinued because of severe cardiovascular toxicity.
The FDA's clinical hold -- effectively a "stop work" order triggered by unexpected safety issues -- suggests that regulators are also concerned about the safety of IDX-184. In order to get the clinical hold lifted and continue development, Idenix must now convince the FDA that IDX-184 doesn't put patients' lives at unnecessary risk. (At least one patient in the Bristol-Myers study died.)
Let's start with the good news by diving into some chemistry. IDX-184 and BMS-094 are both nucleotide polymerase inhibitors and, structurally speaking, 2′-methylguanosine (2′-MeG) triphosphates. When BMS-094 breaks down in the body, it produces 1-naphthol, a toxic metabolite possibly responsible for the drug's side effects. However, metabolism of IDX-184 does not produce 1-naphthol. Furthermore, while Bristol-Myers' compound showed evidence of mitochondrial toxicity in cell line studies at relatively low concentrations, IDX-184 has a wide margin of cellular level safety......Continue reading @ The Street
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