Replies to post #999 on Idenix Pharmaceuticals (IDIX)

[go seek]

Yours is a plausible argument...

One could speculate ad infinitum, and that is part of the learning process we all go through.

Perhaps, early on, IDIX thot they could replace ribavirin w/ NM283 and in early 2006 they were thrown a major curve with the GI effects @ higher doses. I dunno. JP does seem to be hedging more lately (last CC) in mentioning use of 400mg dose and speaking of the differences in SVR Europe and US populations.

This is the first time i heard him use the "magic" word for ribavirin, but as i understand it, its mechanism of action is not well understood.

You did see the NVS/IDIX interview from Oct 2005... see link.
http://www.investorshub.com/boards/read_msg.asp?message_id=19225744

In hindsight, it was a mistake not to include riba from the beginning.

283 + peg produced PCR neg of 62% in an earlier study... 24/36 wk correct?.. and was 53% @ 48 weeks.

There has been a change in the CMO... and NM283 has been in development for many years...

The data from the 283 peg riba study is no doubt much anticipated. I remain optimistic that 283 will find its niche in HCV therapy.

[DewDiligence]

>If the interaction study turns out well, he loses because it reminds everyone what a boob he was not to include triple-therapy studies in the plan from the beginning.<

JP has nothing to be ashamed of. Running phase-2 trials without riba was a calculated gamble taken with the full support of NVS. If a company isn’t willing to take a calculated gamble, it shouldn’t be in the drug business.

As goseek said, the companies did not expect the severity of the GI problems that occurred at the 800mg dose. Had phase-2 been able to continue with the 800mg dose, riba might not have been needed and we probably wouldn’t be having this conversation.

[dewophile]

handicapping drug interaction study

I kind of look at a statement like "We don't know what kind of magic ribavirin does , but we know it does some kind of magic" as more of a positive indicator of success in the trial. This tells me ribavirin's activity at the polymerase likely plays a more peripheral role in its true MOA. The fact it acts primarily to decrease relapses more so than suppressing viral replication points more to an immune-modulating role. The former action could very well lead to competitive inhibition with nm-283, whereas it seems highly unlikely for a negative interaction visa vie some "magical", as yet poorly understood immune-modulating effect.
regarding the in vitro assay..I could definitely see some negative interaction in a test tube through competition for the polymerase site, but aside from just an inherently poor ability to translate findings in a tube to the complex in vivo milieu, most notably the test tube did not contain a functioning immune system