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ArQule Inc. Message Board

  • one1badbilly one1badbilly Sep 2, 2011 5:40 PM Flag

    xalkori

    RE XALKORI some additional info here:

    http://cancergrace.org/lung/2011/08/27/alk-inhibitor-xalkori-crizotinib-fda-approved-new-era-with-new-challenges/#more-5592

    Also some (dated) perspective re ARQ 197 here:

    http://cancergrace.org/lung/2010/08/05/arq197-schiller-asco-2010/

    a little more on both here:

    http://pharmastrategyblog.com/2011/06/met-amplifications-and-resistance-to-egfr-therapy-in-lung-cancer.html/


    Not an expert but it appears that xalkori is targeted at alk, versus 197, which now looks to be being set up as a general purpose met 'high' inhibitor combo therapy. Indeed arq 197 might in combination with xalkori provide additional improvement for alk, as it is hoped it will with tarceva for met high EGFR and KRAS. (per the third link xalkori appears itself to be a met high inhibitor, but apparently weak, so my assumption is that the alk ma is something else/additional targeting alk(?).)

    Others can chime in with more informed inputs here but as I see it xalkori ma looks to be targeted at alk, prima facia not likely to have a huge overlap with arq 197 should arq 197 prove to be as active in p3 as it was in p2.

    Clearly murky stuff, no wonder the investment community is leary.

    Would be nice if mgmt had someone technically credible write an industry article clarifying and show some interest in their stock price and valuation, letting it get trashed, if not justified, is not a smart 'who knows what the hell the future holds' business strategy.

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    • What really makes Xalkori more effective is the testing they do to see which patients will probably benefit the most from their therapy. We know from the Phase 1 and 2 trials that clearly some patients benifit from ARQ-197. To get to the tipping point commercially, ArQule has to be able to show that a certain subgroup of patients would have a greater chance of some benefits in their therapy as oppose to another. These are life and death decisions for the patients. Hopefully, the ARQL team is gaining some good insight from these trials to better target their therapy. Xalkori's success shows that you only have to help a small subgroup of patients to be able to make a big impact.

      • 1 Reply to brsign
      • thanks for a rational response, although I don't think you've hit the mark on where ARQ-197 fits in, it's clear that ARQ-197 is not being pursued as a genetic variant targeted treatment, rather it appears to be working well as a met 'high' co-therapy along with the targeted agent (e.g., tarceva for the current p3 trials). Something like 20% of the EGFR gene variants (KRAS also has a met high population see the first link in my above post) exhibit progression associated met high characteristics. This puts ARQ-197 in a unique position, 1) it is not being targeted at a specific gene variatant, and while this is counter to the prevailing first line strategy for cancer treatment (where a one size fits is out of date), nevertheless in the limited NSCLC domain, a met high inhibitor co-therapy can have an important contributing theraputic role. Hence, as I read it, ARQ-197 is indeeded being tested to play this supporting role across the genotype variant board. This is clearly different to xalkoria (except for METmab of course) vis a vis xalkoria, an potential with something like a 20% market share of all NSCLC, not 4%. That's the point.

 
ARQL
1.17-0.04(-3.31%)Sep 18 3:59 PMEDT

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