"Why all the interest in a startup biotech with drugs that are almost exclusively kinase inhibitors if immunotherapy is going to cure cancer?"
Recent advances in liquid biopsy platform technologies appear to suggest that the cancer genome is far from static - continually evolving and morphing with variables of disease stage, onset of metastasis, treatment response, onset of treatment-induced resistance, etc. Patient-driven treatment guidelines would certainly appear to be in the cards...though I suspect that kinase biology must of necessity integrate with immuno-biology. I doubt either alone holds all the answers. Halting progression, re-staging disease to a treatable condition, possibly even creating temporary remission seems well within the scope of existing TKI. Expanding on that role to create durability of response seems to be a function of immune response - at least that's my gut read. Check out recent AACR presentations from Exosome, Qiagen, Biocept, and PGD. The Biocept presentation on MET amplification in NSCLC looks like their platform could easily find its way into future Cabo trial application. Wow!
The E1512 reporting at ASCO will provide a lot of insight into future trial design. Participation requirements of archived tissue sampling, MET expression, biometric response to therapy in each cohort, and interpretive analysis of correlation to survival benefit were designed into the trial. I may be mistaken here, but I don't believe we've seen this type of reporting to date in any Cabo trial in which response has been compared to another TKI. My initial gut response to last year's E1512 top-line reporting was that perhaps the importance of MET expression in determining NSCLC treatment has been under-recognized...and perhaps even undervalued. I like the fact that E1512 is being reported by the NCI...the good news will be impartially delivered. Last time I looked, publishing oncodocs Joel Neal, Heather Wakelee, and Suresh Ramalingam (sp?) had no conflictive disclosures. It'll be interesting to see if those non-disclosures hold thru positive results.
You piqued my interest, so I went looking.
Lengauer is a keynote speaker in Berlin at the Shiftung Charite' on 5/28...
His introduction on the scorecard refers to him as Blueprint's CSO & Chief Drug Hunter...
Sounds quite dashing, doesn't it?...as if he's on Global Safari...shades of Robert Mitchum as the GWH... I'll keep an eye on Blueprint - thanks for the heads up...
"1993 federal legislation requires insurance to cover medically appropriate cancer therapies."
OK. Let's look at this...
Are you suggesting that a drug - unapproved in any indication - can be be prescribed and covered by insurance...even though there is no approved data outside the experimental stage?
Without NCCN acknowledgements, without an existing NDA, and without administrative endorsement of existing data...
Would someone please explain to me how that system works?
There are no exemptions to enable legal prescription of which I'm aware - and if there were such a thing - i'da been payin' out for LSD/ mescaline/ peyote/ shroom prescriptions many, many years and long times past. Sorry...but I suspect y'all are amiss in this... I don't it.
"Insurance might be an issue..."
Yup. Off label prescription implies that there exists a current label. Cobi is unapproved everywhere you look. What are you thinking?
Joe, I've been hopeful you'd respond in this timeline. If you've listened to the CC, gimme yer take... I concur with Duck's "tell" posting, and nothing less than planned PFS achievement seems in the cards.
You see this any differently? Are we missing something?
"With positive data, Doctors are likely to begin prescribing it off label before approval."
In a world where money rules, anything is possible.
But - without an NDA approval status...no payor will consider paying for Cobi.
At this early juncture, if Cobi is being prescribed, the onus of liability is carried by the prescriber.
I don't expect to see this happen to any revenue-driving degree. Sorry, but that's the game here...
Cobi revenues are bound to a first approval, and I dont see that before PDUFA. JMO
This is a great question, and I think that the answer lies under the heading of "other outcomes"...and is one of the reasons I believe there is so much interest in the ECOG/ACRIN E1512 trial. These two trials share some commonality in that both are gathering data to correlate MET expression and response to therapy to survival benefit - both PFS and OS. These data could effectively turn Cabo into a biomarker-driven treatment resource by defining the most responsive patient group. I am cautiously optimistic that we are closing in on a genomic assay driven application for cabozantinib that has not yet been aptly described in the literature. Just an informed hunch at this juncture, but ASCO should prove revealing...
"...trial would have been stopped..."
I've considered this scenario at length, and concluded that Cabo's optimal commercial potential lies in distinguishing itself from other TKIs. In mRCC, that means it'll have to find a competitive spot in the post-sorafenib treatment algorithm with Axitinib, pazopanib, and sunitinib. Doesn't this line of thinking preclude early trial shutdown for presumed efficacy?...or am I missing something?
I think the Cabo/erlotinib combination has drawn great interest, and nowhere is this more apparent than in the E1512 clinical trials dot gov stats. Though the trial description suggests an estimated enrollment of 117 patients, there are 371 study locations listed. Doesn't this suggest that this P2 population could be much larger than initially designed, and perhaps even large enough to file a sNDA post-presentation..?? I figure this ASCO presentation has high news potential...
"...short lag in reporting final results..."
It may be strategic. JMO, but I suspect the onset of good news to be accompanied by a SO. COH has dropped below $200M - a condition that has shown historic precedence in triggering an offering. Though I realize guidance suggests cash good thru Q1 2016, I expect an offering with some combination of news events regarding Cobi, Cabo, and ASCO. As it stands, existing guidance pretty much aligns anticipated Meteor results with the Cobi PDUFA date, doesn't it? Add on news of European marketing authorization for Cobi - and bingo - we're back to $8... Another offering at that level would fund Celestial, wouldn't it?
"Isn't that kinda big news?"
Maybe...we'll know with ASCO. The one-liner PR last year was that the primary PFS endpoint has been met or exceeded - results will be presented in Chicago in the coming month, preserving first authorship. I expect this presentation to be a hit.
This topic has been covered at some length. This is the E1512 study comparing Cabo to erlotinib and also in combination with erlotinib. See the prior postings...
FTD is.a consideration that must be applied for - the qualifying criteria must be met for consideration. You are confusing FTD with Priority Review, which comes later in the process. Fast track designation is fairly easy to get from the FDA - there exists a lot of unmet need in numerous serious conditions. Actual data considerations come later...and only if agreed upon endpoints are met or exceeded. See FDA Guidance for Industry, May 2014.
It's interesting to note that this OC trial was suspended just last December for planned interim futility analysis, and a decision was made to continue. Being that there is lots of strong rationale for the combo of PI3K and MEK, it could simply be that SA wants out of that crowded development space...or, it could be that SA has decided to buy Exelixis, and discontinued the OC trial because EXEL already has a very effective MEK inhibitor, and SA has elected to discontinue its work-up with Merck's pimasertib. I can't find any indication that they are abandoning the development of xl-765. With no stated reason for the trial discontinuation, we simply may never know...
"Great work. Thank you."
Once again, Nomad...thank you for your valued contribution.
When you and dansmiley get together for strategy & planning...
Who's taking it the old-fashioned way...and...
Who's giving who the reacharround-pleasure-wand-strokin'..??????
Dan oughta be happy to bump uglies with a wizard like you...
"Simply there's nothing good to say about."
I'd listen to Emanuel's advice. Here's why...
8 posts | Last Activity: 6 minutes ago
Member since: Apr 27, 2015
"The poster has a valid point."
The poster has worked his brain to a blister trying to validate his short. So have you...
Abstract submission guidelines determine which data get to present at venue, and abstract update guidelines aren't a matter of "working a little overtime" to overcome...
Your impatience gives you away, Shorty...
Immature data for pt #2 - the reason is obvious to all but you.
Were you dropped on yer head as a child?