Exelixis, Inc. Message Board

Onco,

Point well taken. Thank you.

Nomad,

for what it's worth, I don't think oncodoc and I disagree a whole lot. I think we both agree that based on the thyroid data, Cabo is likely to be approved. Once approved, it is possible to get some off label use. The degree of that use and reimbursement will depend on what other data are out there. With robust data suggestive of benefit, NCCN recommendation can allow earlier use of an agent prior to actual FDA approval. I thought we had a good discussion and do not consider him or her "punked", but a valuable opinion on the MB. There are enough unknowns as Cabo moves forward to make all of humble and we need to be respectful that nobody has the perfect crystal ball.

GLTA,

The "Wiz"

LOL...

Hey "FAKE ONCO"...you tried to spin it in a positive, but the "REAL ONCO" came here and put you in your place. All you kicking, whining and screaming won't change that. You got PUNKED. This is for you my man...

http://www.youtube.com/watch?v=jsaTElBljOE

I agree with the "Other Oncodoc" :)
My point is that while the FDA is critically important for initial approval (in fact requisite), subsequent usage in many settings, not just Prostate, is not quite as rigorous given the impact of the NCCN, and the growing dependence upon NCCN by all Payers including Medicare/Medicaid. The "first" approval is the hardest, subsequent usage tends to be more science and "expert opinion" dependent. Again, the science needs to be good, and there needs to be a clear benefit, particularly in situations where there are other good options.

There are many drugs I use daily that don't have "FDA Approval" in the strictest sense.

On a side note...I saw a response here by Nomad, which I can no longer see since I put him on ignore. Nomad swore off this Board, and not surprisingly is back at this time...with one clear purpose in mind....his role is as a hedge fund short, or sub-contractor of the same, to try and constantly put negative sentiment (note how carefully did not use the words "information" or "data" beccause if you'll read what he says it does not contain new independent information, just emotional spin) out there to dampen enthusiasm and if not drive a stock price down to then at least try to retard it's upward growth to the best of his meager ability. I hope people viewing here are fully cognizant of this, and I hope they understand that the impact by such little worms is about nil. You might then say, "why even comment;" here is why: it is nice to converse with people who have areas of knowledge or extertise not in just the clinical science of a drug (as I do) but also have knowledge about the whole process of bringing a drug to the marketplace effectively (which I do not). Mosquitos like Nomad just buzz around your ear and annoy when adults are tryng to have an intelligent conversation around the campfire. So Nomad please "swear off this Board" again, and don't come back for real. I would also ask that all others here put him and subsequent users that post-like him (and thus likely are another alias) on ignore. Perhaps over time he will then just go away. Don't bother responding to me Nomad, I won't be able to see it.
Thanks all for stimulating discussion. I'll check in periodically and offer what I can as a busy Medical Oncologist working in the trenches!
:)

Once again, the "real" ONCODOC just plain makin' sense. Kudos Onco.

Onco,

I agree in general. NCCN can review high quality data and give a pronouncement much faster than FDA. As you referenced, the data have to be high quality. Typically that means randomized, and well controlled, with positive results. I'm not sure how NCCN will deal with a marginally positive pain result in prostate cancer. Obviously, in the case of a home run (clearly positive with miniscule p-values, etc., acceptable side effect profile, good QOL data, etc.), they would recomend it (as likely would the FDA at some point even in the absence of an SPA). For prostate, it will be hard for NCCN to recommend Cabo in advance of all the new agents in prostate cancer with demonstrated improvement in survival. What that means to me is that if (and when) an NCCN recommendation is given, it will be after everything else and not until the data from COMET-1 is out, which is in several years. I don't think any of the cohorts from the RDT will yield the type of robust data for which NCCN would make add Cabo to the formulary, so additional trials will be required. Obviously, I'm happy to be surprised on the upside, but EXEL's pattern has been to present their most positive data as quickly as possible so I'd be surprised to see huge changes with more data maturation. And before I get bashed, yes, this is a guess and could be wrong.

GLTA,

The "Wiz"

It depends on the quality of the data. NCCN carefully reviews the data quarterly and then make an "expert opinion-based" guideline recommendation. Typically with a drug like Cabo it would be the sort of data that the FDA would likely also approve, but the FDA moves much more slowly than NCCN.

An example might be: Cabo gets approved for MTC. Dosing and safety guidelines are established for this approval to take place. Docs start using it, people "talk" about Cabo at meetings and tumor board conferences. Good Phase II data comes out showing PFS in hepatocellular (HCC), for instance. The data for HCC gets submitted to the FDA, who will take 6-18 months before decision, but NCCN puts it in their guidelines 3 months after data is published. Payers likely would then pay for Cabo post Nexavar progression in HCC. We use it for years like that and then get an email stating FDA has approved for use in HCC....
;-)

Thanks again. If I read this correctly then all the phase II studies upcoming would set the stage for possible NCCN "approval" for off label applications, but this would be generally in very ill patients who had failed on standard chemotherapy. In general this seems to be a pretty tough game, testing new drugs on pts. that are very ill, hoping that you get OS data that will impress the FDA.

Very frequently. In fact most drugs are used technically "off label." The FDA indication is by far the most narrow usage of a drug, especially an oral. Oncologists primarily use NCCN guidelines, not FDA indications. The exceptions would be very expensive IV drugs because the oncologist in an audit would potentially lose a lot of money, and in drugs with very scary blackbox warnings...then we stick to label (or at least I do). Orals like Cabo don't have that same risk exposure.
So what could happen is FDA approves for MTC. Cabo starts getting used. Other data comes in for prostate, or others, and if the data is sound the NCCN may list Cabo as an option post "x" treatment failures. Drug reps aren't allowed to talk about off label uses but everyone keeps up to speed on NCCN guidelines and so Cabo starts getting used more frequently in the other settings and moving up in line of therapy. All this is usually pending FDA approval anyway since the data has to be good in the first place.

"I look forward to seeing the data."

As do I. Data is what has, and will, drive the value of EXEL. I continue to maintain that cabo efficacy is the primary driver and any side-effects will be manageable given the results seen to date. So many patients have had long-term exposure to cabo that effective dosing regiments are becoming well established; as well as doses leading to adverse events in SOME patients. We are not talking about a drug in PhaseII trials with marginal efficacy.

I appreciate your input.

Joe