Replies to post #142277 on Biotech Values

[biomaven0]

The other possible complication with MetMab is that this class of antibodies appears to sometimes act as an agonist of cMET instead of an antagonist. Genentech claims their one-arm antibody design prevents this, but who knows if they are correct in all circumstances.

Aveo's recent upside-down result (assuming for the moment it was not just a small-numbers subgroup issue) possibly adds weight to the notion that there is something weird going on.

Peter

[DewDiligence]

There are many examples of non-target population with worse result, for example, Iressa (EGFR inhibitor) for those without EGFR mutation.

Vectibix had the same issue, IIRC.

[iwfal]

Kinase-actor drugs and their dichotomous action on tumors (inhibiting the growth of some subsets and significantly accelerating the growth of other subsets):

Having now looked through a variety of kinase-actor drugs I would speculate that it is actually more the rule than not that this class of drugs works very well to retard tumor progression for some cancer subgroups, while at the same time significantly accelerating closely related tumors. Some of the drugs for which this is true:

MetMab - retards Met+ nsclc, hugely accelerates Met- nsclc

Gleevec - greatly retards some KIT related variant, hugely accelerates others.

Iressa - retards tumors with EGFR mutations, accelerates tumors without those mutations.

Vectibix and Erbitux - in KRASm CRC the tumor growth is accelerated, but it works quite well in patients with wt KRAS.

About the only such drug for which I looked for this effect and did not find it was Nexavar and its compatriot.

Interestingly the lesson I take away from this is that if you are putting such drugs through the clinic it behooves you to predefine a set of subtypes and check. If you do this you are likely to find some stellar efficacies and some subgroups to stay away from. If you do not do this checking of subtypes you may not reach clinical success, and even if you do the success may be much more middle of the road (vs a "Must have and can charge anything they want because it has unmatched efficacy")

Comments welcom