Replies to post #130033 on Biotech Values

[mcbio]

If you think mapping historical data onto your trial is difficult ... it ain't nothin' compared to trying to map Response data onto survival.

Yeah, I was wondering how a CR would be applied to OS numbers. The OS numbers are expressed as a length of time but with a CR, there obviously is no event so seems confusing to me how this could be included in the OS numbers and expressed as a length of time. (Maybe it's just as simple as calculating the time the patient began therapy until the time the trigger is reached, but I suspect with your response it's far from that simple.) I assume you can't exclude a CR from OS data since CR is the holy grail behind any cancer treatment and it would be unfair to exclude that. Anyways, hopefully there are more CRs in this Phase 2 trial and hopefully they occur in the selumetinib arm.

Separately, regarding your comment on the estimate of blended median survival of between about 10 and 12.5 months for the selumetinib arm, do you have any comments on the likelihood of selumetinib being stat sig on OS if the OS numbers come in at, say, 11 months for the selumetinib arm, and, say, 8 months for the control arm? Is it likely that would be a stat sig OS benefit? I'm not 100% certain on whether or not this melanoma trial is powered to detect stat sig on OS benefit. ARRY's prior comments on powering were just specific to the NSCLC trial, but I'm not sure if that's just because that only came up in connection with a question that was specific to the NSCLC trial (and not also the melanoma trial) or if the lack of reference to the melanoma trial means that this trial is in fact powered to detect a stat sig OS benefit (the primary endpoint of this trial).

[mcbio]

ARRY @ Piper (11/29/11)

Not sure what in particular you are asking - so I may be overly rudimentary in my answer. Most time-to-event trials are ended when a certain number of events are hit and that number of events is normally a fraction of the total enrollment. For cancer OS it is generally around 75% - but I've seen low 70's and high 70's. (Note that for other endpoints it can be substantially different - e.g. PFS is often in the 60's because of the higher rate of LTFU)

Just listened to the ARRY presentation at Piper today and Conway disclosed that in the ongoing Phase 2 selumetinib combo melanoma trial w/DTIC with OS as primary endpoint, the trigger is indeed 60/80 patients, or 75%, which of course has not been reached yet. The trial has been fully enrolled since March 2010. DTIC alone (the control arm of the trial) showed about 8 months OS in the recent Roche trial (#msg-68577942 ) in what I believe is a fairly comparable patient population. Would you care to wager a guess on how likely it is this trial could show stat sig OS benefit for the selumetinib arm if the DTIC control arm shows the same 8 months OS numbers (no guarantee and clearly an assumption here) given length of time the trial has been fully enrolled and fact that they still haven't reached the trigger?

Management also mentioned here that they are seeing very exciting single-agent data for MEK162 in NRAS and/or BRAF mutant melanoma patients in the NVS trial. They hope to have data by ASCO 2012.

Conway believes that the two ARRY MEKs plus the GSK MEK are the leaders in the MEK space and that they "will have a big coming out at ASCO this year [2012]." (The full Phase 2 selumetinib combo data should be released in both NSCLC and melanoma along with the MEK162 data.)