well there is an important distinction (though who cares at this point with us selling at less than a year ago) but anyway the ARQL ph 3 study is based on the post ph 2 analysis that showed stat significance for non-squamous nsclc (they didnt' reach stat significance for squamous+non squamous). Also in ph3 they are looking at kras in particular, again stat significance was reached in ph2...but with caveat that it was post ph2 analysis...always suspect
It did seem a little strange but as far as I'm concerned the broader net they cast the better. I do think this management team know what they're doing and seem to take very deliberate steps with these trials...we shall see! We now have about $137m in cash so the market is valuing everything else that Arqule has at about $100m. The challenge right now is that there isn't likely to be much news flow for the rest of the '11, unless we get lucky with HCC trial. Biotech has had a tough couple of weeks, that's for sure.
No, this study design make perfect sense for two reasons. Erlotinib is used for treating NSCLC in patients with EGFR mutations, so not having erlotinib in the pacebo arm would be unethical to withhold this drug...
Second, ARQ-197 is a c-MET inhibitor, and when used in combination with an EGFR inhibitor(such as Erlotinib), the efficacy of the combination should theoretically be better than either drug alone. Why?
1. Eficacy from the ARQ-197 (the c-MET inhibitor) and
2. The efficacy of Erlotinib should be enhanced due to the c-MET inhibition
The theory behind this combination is that their is a synergistic effect with these two drugs simply based on how the mechanisoms of how these two drugs work and how c-MET inhibition can "enhance" the efficacy of anti-EGFR therapy (Erlotinib).
I would like to see a three-arm clinical trial: - ARQ-197 (mono) - erlotinib - erlotinib + ARQ-197
Why? Because - Presently, erlotinib is a standard of care in NSCLC. So, this arm is a must - erlotinib + ARQ-197, with a potential synergy, will provide OS benefits with a straightforward marketing - erlotinib is also a very expensive & very toxic drug. Consequently, if ARQ-197 mono-arm shows non-inferiority to the erlotinib-arm, a marketing home-run is guarantied.
genether...my apologies...re-reading, I'm a bit confused. This new ph 2 trial does not have tarceva in the 'compared to' arm. My understanding is that the reason for this trial is that basically for patients with kras mutation, tarceva does not work. So the intent here is to see if 197 combined with tarceva would work. In the ph 2 with 197+tarceva vs placebo+tarceva, indication was there was activity based on kras mutation sub-group analysis...and my guess is that's what motivated this study.
So, if this hypotensis is true, then the combination of ARQ-197 + Erlotinib, should be better than Erlotinib alone. That's what the trial will hopefully prove to be true...
If so, then ARQ-197 will become an instant commercial success because its indication will likely be paired with Erlotinib and will gain broad adoption very quickly in the treatment of NSCLC as the first "smart drug" combination therpay.. and all current Erlotinib users will begining using it... So the uptake should be much steeper than a tradition drug launch as a single agent!