Replies to post #35926 on Biotech Values

[gofishmarko]

Re : IDIX - Pegifn / VRTX - rash

>>I'd imagine that if a patient fails to respond to Pegasys that many would try peg-Intron on the second try<<

**True. SGP even has an indication for second-line treatment in Europe.**

Dew ,

I suppose the label for second-line use must mean that there is sufficient trial data to support the hypothesis that nonresponders to Pegasys are more likely to respond on a second try using Peg-Intron ( assuming superiority was demonstrated , for the sake of argument ). It makes sense when you consider that there are a dozen or so subtypes of alpha-ifn produced by the body , probably each with some ability to solve a problem ( e.g., a particular viral mutant ) that others can't. Of course there are other differences between Pegasys and peg-Intron relating to pegylation rather than the single amino acid difference between the two that could account for some , or all , of the differences in clinical results.

I'm thinking about this again in the context of the 'creative approach' IDIX has promised in dealing with nonresponders in upcoming trials. One possibility I suggested previously was designing a trial ( or trials ) where nonresponders to one type of pegifn are treated with NM283 plus the other type of pegifn , compared to a control arm w/o NM283 , both w/ or w/o riba depending on the results of riba interaction studies.

The other option is to use a combo of both pegifns , using around a half-dose of each , I suppose , to try to inhibit the emergence of resistant strains to either. I don't know of any studies where this has been tried , but I'd be surprised if that's the case. Another possibility is a staggered , first week on one , the next week on the other , etc. , approach.

re: VRTX

You've seen all the discussion about rash as a SE in the VRTX P2s , which , as you noted , should be discounted since it's a double blind trial. However , I'm wondering if anyone has ever detected an association between SVR and 'immune breaktrough' events , like rash , during HCV therapy , in the same way that recent studies have shown such an association with antitumor response using MDX-010. The same sort of tolerance-breaking could be occurring , and it could turn out that that the VRTX regimen evolves into a "treat-to-rash" protocol , if this was indeed found to be the case.

FWIW