"Clinical Cancer Advances 2016: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology" published in the JCO 2/4/16. Cabo grabs some good coverage here for thyroid, RET-mutated NSCLC, and RCC. Lots of good overview...
"Perhaps we need a little of that Mary Poppins Magic..."
If a Snickers Bar can transform Danny Trejo into Marcia Brady...
... and Willem Dafoe into Marilyn Monroe...
I'm guessing a single bite into that nutty coco bar would transform Seymour...
Into either Mary Poppins or Hillary Clinton - or perhaps both, simultaneously...
In a changing world, even Seymour wants to be more...
Just for the record, IR also reaffirmed guidance for CABOSUN top line results in first half 2016. Ms Hubbard has proven to be the most responsive of correspondents, and I encourage those that have not utilized that resource to do so.
I queried IR for info, the reply below:
"As we said at the time of the OS topline
announcement, we are targeting presenting the OS data at an upcoming major
medical meeting, so no, we won't be discussing the specific results at the
Leerink conference. But certainly Mike will be talking about them
qualitatively and how they complete the full clinical profile of cabo and
position cabo in the marketplace. Just so you know, the format for
Leerink is actually a Q&A session between the analyst, Michael Schmidt,
and the company CEO's, which is of course Mike Morrissey in our case. Not
a formal presentation. Michael Schmidt will lead the discussion."
JMO, but I don't expect much revelation from the LEERINK Q&A w/ Scmidt as Q4 & FY 2015 reporting is likely before end of Feb. MMM won't give up much before that time...
"...do you know data for AUY922...?"
High incidence of visual disturbances - and additional side effects - have convinced me to look toward the next generation of HSP90 inhibitors. FWIW - I don't think luminespib has yet generated enough convincing data to move the drug into pivotal analysis. Another FWIW - the FDA.gov site has a lengthy presentation providing overview analysis on the promise of ganetespib (dated Dec 2015) suggesting they see value in the future prospect of HSP90i, despite Synta's dismissal of further development.
I'd be very, very careful wrt investing in any HSP90 technology till there is is a reliable predictive assay. Novartis gave AUY922 back to Vernalis in Dec 2014, and that program has completely stalled. Development of Ganetespib has practically BK'ed Synta. A serendipitous synergy might play for XL-888 in melanoma, but to date - no one has stepped up to the plate. I don't doubt the hypothesized efficacy - there have been some dramatic, notable responses in lung & breast cancers. However, those limited successes have proven ill- defined at best, and -at worst - non-reproducible in clinical practice. Too elusive a science for me... All well-rationalized therapeutics will have their share of non-responders, limited responders, and exceptional responders - but successful commercialization must embrace an unwavering predictability of response...and I've yet to see that in any HSP90i...
"...I think they will shoot for the March NCCN meeting."
It is a very appropriate venue, their agenda being "Advancing the Standard of Care". To the best of my knowledge, the abstracts at NCCN have never been availed public viewing. It's a closed affair. That said - they've only had poster presentations a couple years now, and all that may be subject to change. Again, it is a most appropriate venue, and NCCN expertise will undoubtedly be called upon to satisfy the treatment algorithm. Looking forward, it makes great sense to address prescribed sequencing prior to approval, and I expect to see an upsurge of KOLs lending advice on how best to proceed as the new algorithm evolves.
"...did you know that I know an employee of Exel....?"
Yessirree Beijing Bob...
There's more than a few of us that have seen him doing you in the patootie in the men's washroom at Cecilia's Pizzaria on Grand Ave. Might be best to keep it private, you silly little yellow man....
But it sure is funny how you smile each time he grunts...
Do you enjoy the marinara too...??
"I don't think the prior Nivo treated subset from Meteor gets much notice, the sample size is too small (n=32 split between the cabo and ever arms)"
If it weren't for the rationale that the NCI is pursuing with Nivo/Ipi/Cabo, I'd agree. But - these compelling numbers fully support the PD-1i/ Cabo combo rationale, particularly with consideration to Nivo's recognized delayed response and lengthy half-life. The trigger will be a move toward a P2 trial. If P2 is decisively skipped (AKA V/C in melanoma) - the fuse would be lit. I see breakthrough status as a distinct possibility spinning out of the Apolo studies. A favorable impact on SP could easily be predicted if a move to P3 is made in 2016...
To my thinking, that would be the ultimate catalyst toward a favorable JV...
"Any idea when the full data set will be presented?"
June's ASCO annual meeting is the most likely venue, though I wouldn't omit the possibility of an NCCN presentation in March. The AACR-JCA is only weeks away, and is doubtful - even for an LBA. Inopportune timing. I remain watchful, but there aren't too many possibilities that would have the peer impact of those first two... the NCCN annual meeting is still accepting abstracts.
I expect to see a pre-ASCO approval, so we may see the market labeling prior to the PDUFA date of 6/22. Leaves lots of time to bet your horse...
Or cover your short...depending upon in which camp you reside...
"...also agree that HR is a better indicator of benefit than mOS comparisons."
I think it's also important to attempt to understand how the algorithm will realign to accommodate these new approvals. What treatments will be displaced? What treatments will be reinforced?
Your statement regarding the marketing importance of HR makes me consider that Cabo will capture ALL those previously treated with anti-PD-1i - non-responders, those that progress, and those that can no longer tolerate the regimen. The Meteor subgroup HR of .22 should carry the weight of clinical reasoning. How large is that patient pool, and how many of those patients will not consider any other therapeutic other than Cabo per that .22HR. I suspect most of them...perhaps all of them.
As the algorithm continues it's shake out, and Nivo displaces sunitinib, Cabo stands to stay in line to advance to maintain a post-PD-1 response rate, failing a similar post-PD-1 response from Sutent.
What be left over for L/E, pazopanib, axitinib, etc. Which will simply "lose out" in this game of musical chairs?
Despite COMET failure and EXEL's deprioritizing of Cabo in the prostate space, cabozantinib is still the subject of many currently ongoing studies in ProsCa... As gains are made in understanding the underlying disease biology, I figure to see Cabo tried in combination with both immuno and AR treatments - if only for the research benefit. Time'll tell. Cabo desperately needs a predictive biomarker of patient response. All JMO...
Thanks for all the inputs this morning. It's difficult enough to wrap your head around today's marketplace - let alone trying to over-interpret a biotech PR. Let's hope MMM's choice of optimistic verbiage doesn't grossly displace the reality of how Cabo fits into real-world clinical usage. JMO, but I suspect he's as excited as many of us to see first quarter revenue numbers post-approval. His crystal ball is no better than ours...
"Moving forward, Exelixis’s Cabozantinib will have to compete with BMY’s already approved Nivolumab. The drug is used to treat advanced RCC and is currently capturing 50% share of new patients. However, the analyst believes that Cabozantinib has an upper hand because Nivolumab is not associated with a PFS benefit. Schmidt continues, “Exelixis’s market research confirms that [a PFS] benefit is important to physicians and patients alike.” Further, Nivolumab does not work for every RCC patient, therefore Cabozantinib could be a strong alternative treatment.
Schmidt concludes that the RCC market can be valued at $1B in worldwide sales and the “market will grow substantially with the advent of newer therapeutic options that provide longer duration of therapy.” Looking forward, “Cabo has over $400MM potential in this indication.”
Schmidt declined to offer a price target on this news. In this market, he'd likely be wrong in suggesting a valuation in excess of $1B. That said, my impression is that METEOR final results have been substantively derisked. The big question from here is whether we get actual OS data as a presentation - or simply get to read it off the labeling... Next stop AACRJCA Maui - the troops could use a winter vacation.
Not to battle the semantics of it, but here's the actual PR quote:
"In a second interim analysis for OS, a secondary endpoint of the trial, the results showed a highly statistically significant and clinically meaningful increase in OS for patients randomized to cabozantinib as compared to everolimus. Ongoing study monitoring did not identify any new safety signals. Exelixis intends to present these data at a medical meeting later this year."
The choice of verbiage in "highly stat-sig" & "clinically meaningful" are certainly open to interpretation, but undeniably smack of positivity...do they not?
Posted by Silas Inman, 2/1/15...
"In the trial, a 5-month benefit in OS was required in order to demonstrate statistical significance. This was equivalent to a hazard ratio of 0.75, with a P value of .0019 representing significance. The company did not release the exact benefit in OS. At the first interim analysis, the hazard ratio for OS was 0.67 and the P value was .005, which barely missed the cutoff for significance. Findings from the follow-up analysis are being prepared for presentation at an upcoming medical meeting later this year."
For my money, to be considered "highly statistically significant" & "clinically meaningful", the trial design would need be reinforced in the vicinity of 10%, suggesting that Cabo hung unto the first interim HR of .67...
And perhaps better...