Idenix Pharmaceuticals (IDIX)

[gofishmarko]

>>> However, Tyzeka / Sebivo could take some of the second-line Hepsera business. <<<

I wouldn't expect this to occur. Telbivudine shares the same flaw as entecavir in this regard -- the same mutations that can confer resistance to lamivudine also can result in resistance to these two -- but adefovir / tenofovir have distinct resistance profiles that make them better candidates for follow-on or combos with lam and the others.

New resistance mutations are discovered occasionally so this is a somewhat fluid model , but I believe it's the one that guides treatment decisions currently.

The other advantage that entecavir has is that it's been demonstrated that several mutations are required for "true" resistance , which is why resistance in lam-refractory pts. builds gradually over years. I'm not sure to what extent compensatory mutations are required after the initial resistance mutation to telbivudine before "true" resistance arises , or whether the single mutations are sufficient.

The extra mutation steps are a big deal because they provide a margin of safety. The danger with these patients is in development of resistance that quickly leads to fuminant hepatitis and , often , death. This is less likely to occur suddenly with the higher genetic barrier of multiple mutations.