This can't be good news for XL184 and MTC:
THe only way this can play out well for EXEL is if FDA rejects it based on PFS not being an adequate endpoint (I would have to think they had an SPA first) and the overall survival data ends up negative (which is could due to contamination by the allowance of cross-over). We won't know for a little while, but it does say FDA will give priority review.
Ernie, any thoughts?
All I have to say is ONCODOC CLEARLY HAS A VERY GOOD UNDERSTANDING IN EXEL'S DEALINGS. Anyone who thinks otherwise is simply MARRIED to the stock and cannot see anything but "roses" when it comes to EXEL. This happens to the vast majority of inexperienced "investors".
Keep up the informative information and opinions, Oncodoc. Please don't let the "perma-cheerleaders" scare you away.
<<FDA tends to worry about anything that might be perceived as relaxing approval standards unless pushed hence my comment that for prostate they have required survival.>>
I don't think it is quite this cut and dry. First, recall that the SPA primary endpoint for the first Provenge trial was PFS, not OS. WRT being perceived as relaxing standards, I disagree here also. Avastin was approved for 1st line BRCA on the basis of a PFS improvement in a trial that was not originally intended to be a pivotal study. My personal opinion is that FDA doesn't like any standard imposed on them other than those they claim as their own. I think the upper management there would benefit from some hormonal ablation therapy.
<<I haven't looked up the trials you referenced on clinical trials. gov, but I would also make a distinction between treatment for bone mets and treatment of prostate cancer.>>
I understand your point, but one of the claims being made is that 184 may have the unique quality of causing disease regression in both soft tissue and bony mets. Our only evidence is a set of before and after scans of a single patient and some vague hints of more to follow. An awful lot depends on the "more to follow" part. If 184 does have some differentiating therapeutic characteristics in this regard, I would not rule out the possibility that a trial could be designed enriching a patient profile for an endpoint other than OS.
Unless I'm mistaken, the majority of HRPC patients don't present with "measurable disease." I suspect that this circumstance has as much to do with a lack of surrogate endpoint trials as FDA intransigence.
We will see where the data leads and watch them go from there.
I'd agree that there are a variety of opinions within the FDA and also within the oncology community. Pazdur's review makes the point that FDA has approved products with endpoints other than survival, however things get broken down further between different diseases and there precedent is very important ( for example, response rate by RECIST tends to be accepted as a surrogate of clinical benefit for breast cancer but not in thyroid cancer [yet]). FDA tends to worry about anything that might be perceived as relaxing approval standards unless pushed hence my comment that for prostate they have required survival. Things can change based on new data, but prostate has been a challenging area, particularly because FDA got burned looking at PSA previously. I don't blame the agency as they get hauled in front of congress when something bad happens and accused of delaying effective treatments to cancer patients when things take time.
I agree that it is too early to make definitive pronouncements about what will be required, but if the RDC prostate data are really good, XL will need to make these decisions very quickly. Don't forget that Cell Genesys failed in prostate cancer, bevacizumab had a negative trial as well, and apparently Sutent has also just failed despite some rationale for doing a large trial.
I haven't looked up the trials you referenced on clinical trials. gov, but I would also make a distinction between treatment for bone mets and treatment of prostate cancer. If XL184 is being proposed as a treatment for bony mets, it is a different space, but hardly an easy one. These trials tend to be even larger since they are usually looking at preventing an event (e.g. Zometa for skeletal events).
This is interesting stuff to speculate about, but I suspect we'd both agree that the path forward will be driven by a more robust data set in prostate cancer where we can get a sense for percent of clinical response as well as magnitude and duration on a patient-by-patient basis. I suspect some of the presentations are designed to attract partner interest because if the plan is to finish the MTC trial, open a phase 3 registration trial in GBM before the end of the year, and shortly open a registration trial in prostate (I'm presuming after SPA with the FDA), there will need to be money to support that.
My take is that despite the enthusiasm on this board, the data presented in November (or maybe even at ASCO 2011 so duration of responses can be fairly evaluated) will be cruicial.
Thanks for your thoughs as always.
If I'm a paid basher, where do I collect my check? If you want to say unpaid basher, one could argue. Not accepting everything EXEL management puts out in an investor presentation or conservative interpretation of early clinical data may make me a basher in some eyes, but I don't see it that way and I'm certainly not getting paid. If you want to argue about how different scenarios play out for XL, I'm happy to speculate, if you want to name call and avoid any facts, you're not helping discussion on the board.
I think you misinterpreted what is in that post. I was responding to a post which I believe implied there would be unblinded phase 3 data presented in that time frame (I do not expect that trial to have results in that time frame, hence my question). The same post notes that the reason for my surprise is that I was only expecting earlier phase data in November at EORTC. (It is fairly typical for phase 3 results to be telegraphed and a big deal). The post is hardly is a statement that I didn't know there will be data updates in November, the issue is what data updates will contain. The other reference you make is actually to another poster who is not me. I'm not seeing where I posted something being surprised at ANY XL data in November as I have always fully expected data updates, particularly from the randomized discontinuation study (and this is even more critical given that BMS pulled out of XL184).
You are free to draw whatever conclusions you want about me and motivations (as I am about you), it's a free world, though frankly, I really don't think any posters on this board can really influence the stock price.
Oncodoc, please refer to the Sept. 3rd thread entitled, "as much as I want a positive announcement."
I stand by my comments about you. I think you are shorting the stock and come off as a "know it all" to try to further your agenda. That's fine, by the way. I don't mind people playing the "don't pass line." At the craps table though at least I can see them right there. You're more of a snake in the grass.
<<Ernie, any thoughts?>>
Of course I do. First, I agree that from EXEL's perspective, it's not good news, but I will point out that it isn't 'new' news. We've known about the Vandetanib results and NDA filings were inevitable.
The Vandetanib trial and the XL 184 trials are very similar---300+ patients and PFS primary and OS secondary endpoints. With or without an SPA, V is a lock for approval. The knock on PFS as an approvable endpoint is that PFS can act like a statistical vernier. In a large trial, small differences in PFS can result in statsig results, thereby acheiving a primary endpoint. In this particular situation, that's not going to be an issue. Even with a relatively small sample size, V showed highly significant results and importantly, a very clinically significant advantage as compared to placebo.
A V approval before EXEL even gets to announce topline results does diminish the psychological boost that will come from a successful result in MTC. The most likely outcome I see is a split market, with V enjoying the advantage of being first. It is possible that there could be a differentiating factor that favors one drug over the other. A perceived advantage in efficacy or safety profile could give an advantage to one drug over the other. It will be a long time until there is any OS data from either drug, but in MTC the PFS data is so compelling, that it will be correctly assumed that PFS is a reliable proxy for OS.
Another outcome of a V approval is that it means that 184 will not get a priority review and that as a "me too" drug, it probably will not even get an ODAC visit.
All of this said, it's just not that big a deal compared to other developments with 184. If, as expected, 184 has filable MTC results, EXEL will still get a psychological boost. MTC at best was a niche indication that had more symbolic significance than substance.