Replies to post #137353 on Biotech Values

[oc631]

We know the RVR achieved with GS-7977 means the level of virus were below the limit of detection but it is possible that there were very low viral titers, below the limit of detection of current assays, which haven't necessarily mutated (nukes do have high barrier for mutation), but simply survived and rebounded.

Absolutely. Dew called me on that one. Do you know if the patients that relapsed in the GT2/GT3 monotherapy study were confirmed to have the wild-type virus?

longer treatment period should do better and we both agree that treating nulls for 24 weeks with just GS-7977+Riba would still be worth, considering current alternatives

I'm not convinced that longer treatment durations will do better but it certainly is worth a shot. Extending treatment durations worked using slower acting interferon-based therapy. Let's see if the same rules will apply in all-oral. If we are dealing with viral rebound the point is moot.

In case resistance did occur, typically by mutation, another drug that induces a different mutation from that caused by GS-7977, should help because multiple simultaneous stresses on the virus prevent these 'drug escape mutants' by repressing selection of resistant variants, which generally are associated with a significantly impaired replicative fitness anyhow. Since NS3a cleaves NS5a to its active form, combining these two complementary mechanisms should be synergistic even if the NS5a inhibitor has a weaker resistance profile

Very interesting and something I didn't know. The study with BMY's NS5A will be quite compelling.