Replies to post #41811 on Biotech Values

[DewDiligence]

Nice post, gofish. Do not be surprised if a facsimile of it makes its way into an article in SeekingAlpha, RealMoney, or some such outfit.

[upndown1313]

wrt HCV combos, gofish I can't argue that your scenario 2 is a lower risk option as it obviously is. You make excellent points wrt to potential regulatory impact. There are 3 points I would like to make though: 1) there is a huge difference in combining inherently toxic oncologic drugs and highly specific HCV inhibitors which are designed to have minimal AE's, and therefore this in itself is a lower risk scenario; 2) Death is not a likely scenarios for these classes of compounds, and the risk of serious AE's is minimal, assuming no drug-drug interaction. Even if there was a drug-drug interaction this would most likely be caught in early PhI trials so that risk could be mitigated before starting more advanced trials. Keep in mind if NM283 was selected, a GI AE in a combo trial would not expected to impact the other monotherapy at all as this was already known with that class. 3) the timing of the combo trials could be staged such that the lead monotherapy could be approved PRIOR to starting any Ph3 trials, again mitigating risk for the montherapy. For all these reasons I still see Scenario 1 as a low risk/high reward option with a potential annuouncement to start planning clinical trials in 2007. The emphasis is on high reward.

[dewophile]

you (and dew) make a compelling argument against combos prior to approval..and that may very well be the case, but just to play devils advocate:

1. the scenario unfolding as you describe is highly unlikely if proper combinations are chosen (in terms of overlapping toxicities, pk, etc.)
2. if prove 3 leaves a lot to be desired there is going to be an awful lot of pressure on the fda and the companies to initiate combo trials in this population representing the single most pressing need for new therapy
3. imagine this scenario: telaprevir monotherapy data looks good (but not phenomenal) in naives and shows some modest improvement in tx-refractory pts..phase 3s are initiated with hope for an NDA in the 2008-9 time-frame. nm-283 also results in improvment over SOC, as does say sgp's or soem other protease inhibitor in development, albeit with lower potency than telaprevir. the commercial potential of these agents is questioned due to the inferior efficacy, so they initate combination trials before telapravir approval and efficacy is superior to that of telaprevir monotherapy, perhaps in both naives and refractory populations. even with a head start of say a year in terms of approval, will patients be willing to wait a bit longer for say a shorter, less toxic, and more effective combination therapy on the horizon, particularly since the overqhelming majority of pts do have time on their side in terms of liver status. is that a risk vertex is willing to take for the extrememly small likelihood of a backbreaking interaction toxicity using agents that have a track record (in terms of class) of successful combination therapy in HIV?

these hypotheticals can cut both ways.. at the end of the day time will tell and I'm really not so sure how it is going to unfold, but i am probably in the camp that wouldn't handicap the odds of combo tx wuite as low as you and dew

PS: i did not hear the workshop..is it archived? link?
tia