Statistically significant only means the error bars of the test arm don't overlap the error bars of the control arm.
For "clinically meaningful", see my response to ernie; but it likely is a response to "MCID" which refers to issue the patient finds important such as reduce pain that is unmeasurable but qualitative and can refer to quality of life
There are literally papers written about the wishy washy statement "clinically meaningful" and "clinically meaningful" is often used to denote quality of life improvements (HR-QOL).
The use of "clinically meanngful" most likely refers to "MCID" which are issues the patient finds important and is unlikely to refer to OS.
hi social, i think only 2 weeks would be impossible given the exel press release stating highly statistically significant "the results showed a highly statistically significant and clinically meaningful increase in OS for patients randomized to cabozantinib as compared to everolimus."
"My fear is that it's only a little OS improvement. Let's say 2 weeks. The implication would be another survival pathway is upregulated giving a poor increase in OS."
They've already promised the improvement is clinically meaningful and anything less than a 3 month separation would represent quite a degradation from what the first interim was indicating. We'll see.
My fear is that it's only a little OS improvement. Let's say 2 weeks. The implication would be another survival pathway is upregulated giving a poor increase in OS.
I don't think that it would prevent approval as along as OS was increase because it's improving the quality of life without more harm.
It's entirely possible for the cMet pathway to be upregulated downtream from where the TKI is blocking it and usurps the affect of the drug. Then combination treatment with HSP90 might be prove useful
If it's a combo VEGF, MET, mTor or HSP treament that's needed, Exelixis may be in a good spot; however, it would have been better to be chasing the data via research this whole time and developing the next gen drug.
"...is there a number that if and when it is released in the near future would make us all stand up and go 'wow'? Its another way of asking, what number is baked into (expected) the SP and what number breaks that threshold and moves it positively? Anyone?"
First, cross trial comparisons are always difficult. I agree that the Meteor population appears to be more advanced than either the Checkmate or L/E trials, so in this case the cross trial comparison is especially unfair. I also agree that HR is a better indicator of benefit than mOS comparisons. All that said, once the regulatory process is complete the marketing starts, and those comparisons are going to be made because those are the the most prominent and eaiest to understand statistics available.
Some of the KOL's expressed a preference for Nivo simply because it was initially the only statsig OS result. It showed a lack of statistical savvy, but it was a predictable response. By the time Cabo (and maybe L/E) hit the market, I think the reimbursement agencies will have as much influence over the treatment algorithm as does doctor and patient preference. I think a better reason to show preference to Nivo is because there is a subset of patients who do really well with some very durable responses including a handful of complete responders.
Back to your question. For Cabo gain a competitive advantage, it would need to show a mOS equal to or greater than Nivo which had a 25 month mOS. That just is not going to happen. We have the KM curve from the first interim and it would need to drastically reshape for that kind of result. I think a more likely outcome is something on the order of 19 months vs 14.5 months for Ever.
Went on the ARIA message board; what a wasteland. Even with all the idiots posting here the EXEL board is light years better.
" We should be happy they haven't sold out cheap to Roche. I still think decision on JV has been complicated by entertaining offers for a BO."
Joe, let's explore this for a minute. Since Roche is already a partner in the Cobi/Zelboraf combo you would assume that they may have a had a peek at how they make the sausage at EXEL. Does Roche have a dog in the fight for supremacy in mRCC? With Opdivo(BMY) sucking out all the air in the room, who will want to enter the fray? A JV partner and or a BO candidate would want to see the final OS details, no...yes??
I don't know the answers to these questions but I wanted to raise the issues. You're input and of course others would be appreciated and now I have a date with a little white ball. GLTA
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Assuming for the moment that the actual OS numbers are not dissappointing but in fact are super highly incredibly stupendously significant and mammouthly meaningful, per the press release, is there a number that if and when it is released in the near future would make us all stand up and go 'wow'? Its another way of asking, what number is baked into (expected) the SP and what number breaks that threshold and moves it positively? Anyone?
Bingo, ditto. Slowly, slowly catching monkeys.
FDA decisions, pipelines and large short interest makes a perfect storm.
If just dependent on FDA decisions & pipelines, the price action is limited to the "market evaluation - herders", however, add in large short interest to the storm, it's everyone for themselves.
GLTA - ARIA was up yesterday.. la la land.. lol
short answer: I'm a firm believer in irrational exuberance.
That and the collective negativity of traders shorting EXEL because they view EXEL valuation as "bottom-line" and show-me-the-money when these same traders wouldn't know the bottom line valuation if it was shoved into a place where the sun don't shine. Immuno-onc has been hyped and sold as the cure for cancer and it just ain't so. Small molecule therapeutics will continue to play a dominant role in cancer therapeutics for many years to come and possibly always because most cancers are not immunogenic. As far as resistance to paying the companies that develop effective therapeutics goes - watch the money pour into any and all companies working on Zika virus or antibiotic-resistant bacteria. Obama just launched a new cancer initiative - more billions into the pot. Effective therapeutics will be paid for and EXEL has developed effective therapeutics.
Mr. Joe, we've heard ernie's view about exel's limited prospects and I highly value his analysis, input, and opinion, the dude is smart, as are you. I'm wondering in light of all aspects and characteristics of his analysis that he's shared, would you be willing to share why you think exel will still be successful rather than have a very limited upside. Thank you both for sharing your collective knowledge.
one of the more intriguing aspects of EXEL is the enduring connection to Biogen. George Scangos and Stelios Papadopoulos are on BOD of both - these guys are some of the best in the biz. Connection to ARIA is Alex Denner, former Carl Icahn protege and head of Sarissa Capitol, a hedge fund. Denner is on BOD of both Biogen and ARIA. I still hold a significant position in ARIA and watch both EXEL and ARIA daily. Most days they trade in lock-step to the hour and in after hours trading to the minute - typically large number of shares traded in both companies at the exact minute for both. Usually ~ 4:30pm. large number of shares 10s and sometimes 100s of thousands of shares traded or "settled" at ~ 4:30pm. Coincidence? I doubt it.
Denner is especially interesting. Bought huge number of ARIA shares when FDA stopped pulled ARIA's drug for tox - blood clots or heart attacks or both. Stock lost ~ 90% of value and Denner bought them up. Forced the CEO and founder out and became CEO last month. Denner had already doubled his initial investment in 2014 and thinks there is room for more. btw. ARIA's drugs are kinase inhibitors and Denner has PhD from Yale and did his undergrad at MIT - dude's a scientist.
For all the justified complaints we longs have about EXEL management, MMM is only the face, not the brains behind EXEL business decisions. BOD is in charge and you can bet there is a lot going on behind the scenes. We should be happy they haven't sold out cheap to Roche. I still think decision on JV has been complicated by entertaining offers for a BO.
btw Ernie, I still think your wrong about EXEL's prospects and hope you jump back in. all serious longs are fed up with amateurish mistakes made by EXEL's management but I think they will be successful in spite of themselves.