Replies to post #75451 on Biotech Values

[mcbio]

Re: VRUS Citi webcast

That’s right—almost any combination of direct antivirals from multiple classes will do a good job of stopping HCV viral replication. The key to a medically and commercially successful regimen is thus safety, tolerability, and complementary barriers to resistance by the cocktail components.

I may have asked this before, but, in general, at what point have prior HCV compounds across all the classes run into safety problems? Is it generally at the 7, 14, 28 day mark, or some other point? Also, I'd assume that the safety concerns have generally arisen in Phase I or Phase II trials, but are there prior HCV compounds that have made it into Phase III before the first sign of safety issues appeared? I'm just wondering at what point, in terms of number of days of treatment in particular, one could have a reasonably good idea that an HCV compound is safe.

By and large, investors don’t yet seem to understand that a great HCV cocktail need not consist of component drugs that are individually great when used with interferon and ribavirin.

I just want to make sure I understand your point here. Are you saying that investors haven't necessarily subscribed to the theory of the need for multiple direct-acting antivirals in conjunction with interferon and ribavirin? And, if the thinking is that only one direct-acting antiviral is necessary, presumably because VRTX is so far ahead of everyone else, that's why it has been assigned such a huge market cap premium over its HCV competition.

R7128 did show kidney tox in monkeys, so it’s not out of the woods yet on safety. The phase-2 R7128+SoC trial includes a preliminary mini-trial in which a few patients in each trial arm are checked for kidney abnormalities before the main portion of the trial can be fully enrolled.

I think we touched on the kidney tox in monkeys before. But I believe you noted that it was only seen at a really high dose, one that is much greater than the doses used in human clinical trials. So, presumably there's not too great of a risk here, but we'll of course have to wait on the data.

A bigger issue with R7128 than the BID dosing is the very large 2,000mg/day daily load needed for efficacy, which may preclude R7128 from being co-formulated into an Atripla-like, all-in-one pill.

That's a good point. Although, how soon do you think an all-in-one pill consisting of multiple direct-acting HCV antivirals will be the norm? Having the potential to be first to market in the nuke class, assuming R7128 continues to prove safe and efficacious, VRUS would presumably be able to enjoy significant revenue until the arrival of an all-in-one pill. The question, of course, is how much time is that?

One plus for VRUS is that they do have the backup nucleotide that just entered Phase I, which is supposedly 20 times more potent than R7128. That could be their answer for the nuke portion of an all-in-one pill. Obviously, there is plenty of competition now in this class.