Smart move. After its approved for MTC, oncologists aren't going to wait for phase 3 data before combining cabo as a synergist (assuming the safety data is good and the dosing is understood).
"Her comment- "think you want to go with what works"..speaks volumes about how much we don't know except this drug has efficacy..."
Makes for interesting conjecture. Makes me consider that minoxidil (Rogaine) was initially developed as a blood pressure medication...of course later finding it's way to managing pattern baldness. A rather fortuitous commercial coincidence...eh?
In this context there is major entertainment value in considering future trial designs for a drug like CABO, as more is understood regarding pathway interactions common to all cancers...and perhaps to many illnesses.
Along the lines of "serendipity" this exchange is interesting-
"BSB: Would we we better off combining separate c-MET and VEGF inhibitors rather than have one drug like cabozantinib that has multiple targets?
Dr Hussain: think you want to go with what works and thus far, this is the first drug that has again what we think is a MET and VEGF targeting based on the preclinical data that seems to work. But would also point that it is not a pure VEGF & MET it also has RET, KIT, FLT and AXL. My point here is, we assume that this is the reason."
Her comment- "think you want to go with what works"..speaks volumes about how much we don't know except this drug has efficacy that others do not and replicating that efficacy isn't as simple as combining agents with similar pathway effects
<<I know you've seen this, what's yer take as far as Dr. Hussain's slant on commercialization of CABO? She seems less than excited about bone effect than I'd have guessed, and is obviously not sold on pain palliation as a guaranteed pathway to approval.>>
Be careful in differentiating between what Dr Hussain had to say and what the blogger's characterization of what the company's program consists of and his interpretation of Dr. Hussain's remarks.
The bloggers comment, "This is at odds with how Exelixis appears to be positioning it. The corporate presentation...had a strong focus on bone mets. Cabo demonstrates unique ability to to resolve bone mets and decrease pain in CRPC one slide said."
The reality is that survival is the primary endpoint of Comet 1 and a secondary endpoint of Comet 2. EXEL is emphasizing the bone met resolution and pain improvement to commercially differentiate Cabo from all the other drugs that have shown a survival advantage but do not resolve bone mets and do not have a pain label, but the Cabo pivotal trials still focus on OS, not bone met resolution. I think the blogger is creating a controversy that does not exist. The one thing Dr Hussain did opine about was that she felt that some more emphasis should have been put on testing Cabo earlier in the disease sequence where she felt that it might potentially have the greatest impact.
In the third BIOSTRATBLOG interview study, where DR. Hussain uses the term "serendipity" to describe the CABO bone effect...
I know you've seen this, what's yer take as far as Dr. Hussain's slant on commercialization of CABO? She seems less than excited about bone effect than I'd have guessed, and is obviously not sold on pain palliation as a guaranteed pathway to approval.
I see positivity here, but it appears very guarded. Any further comments?
<<Maybe I should re-phrase my wording of the previous paragraph and refer to it as the hack job she provided on Provenge. It appears she is following the same path here. In 3-parts.>>
Actually, I read her as being very supportive of the drug. That she is willing to be critical of certain aspects of the development program only contributes to her credibility and enhances her position as an honest observer. MassGen and Univ of Mich are the two foci for the institutional support that Cabo is fortunate to be receiving and she is a playing a substantial role in U of M's program.
One of the things I found interesting in the article is something we have touched on before. She made the point that we assume that Cabo's activity is tied to its properties of Vegf and cMet inhibition, but that has not really been definitively demostrated yet. I find it very interesting that combining other single activity cMet and Vegf inhibitors has not resulted in similar efficacy in disease models. Dr. Hussain made the point that Cabo's efficacy may be tied to cMet and Vegf inhibition, but it may also be tied to a pathway interference that has yet to be described or fully understood.
<<FYI- I am providing 3-links from an interview that was conducted with Dr. Maha Hussain. If memory serves me correctly, she was one of 4 on the FDA Advisory Committee that voted down Provenge.>>
Actually, the Provenge thing was a real oddity. It wasn't ODAC that held the original committee meeting. It was the stem cell/immunology group. Hussain and Scher served on ODAC (oncology) and played no part in the advisory meeting. After the fact, they publicly interjected themselves into the debate and made it known that they viewed the positive recommendation as a mistake. In retrospect, my personal viewpoint is that their stance at the time was appropriate for the facts then in play. Obviously, patient groups and investors are two groups that had a lot at stake in the outcome and the FDA's initial decision was very unpopular with these constituencies. The conspiracy theory crowd has been making hay ever since.
Ernie - Hbomb,
Thank you for the input.
As far as being early, going through an extensive decision-making process, it is prudent to evaluate all alternatives and to recognize any problem awareness.
The final stage is the post-purchase evaluation that arises from a concept that is known as cognitive dissonance.
FYI- I am providing 3-links from an interview that was conducted with Dr. Maha Hussain. If memory serves me correctly, she was one of 4 on the FDA Advisory Committee that voted down Provenge.
Maybe I should re-phrase my wording of the previous paragraph and refer to it as the hack job she provided on Provenge. It appears she is following the same path here. In 3-parts.
While those many cancer drugs seek to extend survival, it has become apparent that they only knock down tumors and extend survival for relatively short periods. The root of the problem lies within the stem cells and their mutations.
Until this is addressed, its just one-upsmanship game costing society and patients in money and false hope.
If you were given 12 months to live. Wouldn't it be worthwhile to gain another 4 or 6 months to your life? And then with the next drug, another 4 months, and another and another, etc? We are all going to die. It isn't false hope to extend the inevitable, and perhaps provide a few more memories, another birthday or graduation, and possibly with a little less pain. Just my humble opinion.
"I would rather see MDV3100 combination vs Abiraterone."
I'll rephrase to state that I would rather see a Cabo-MDV3100 combo vs Cabo-Abiraterone combo. That said, the Abiraterone phase I probably to get the ball rolling here. I would definitely like to see Johnson & Johnson, and Medivation want to combine with Cabo at some point in the future. Maybe setting up competition for the privilege of running phase III trial with Cabo. Probably not, but fun to fantasize anyway.
<<<<H bomb can check, but I think this is a pretty substantial indication numbers wise.>>>>>>
It is estimated that 57,000 premetastatic patients will undergo drug treatment in 2012 per Exelixis latest R&D slide presentation. I would rather see MDV3100 combination vs Abiraterone.
>>>>>We are getting a bit ahead of ourselves, but certainly this is the same thought process that any potential buyer of the company is going through. <<<<< --Ernie
I also think D-mab failure was a huge negative for Exelixis. The clinical development in earlier stage was going to be long anyway, now it is going to be longer if ever, when it didn't have to be that way.(Maybe Cabo was too toxic for premetastatic disease, and Exelixis made the right choice who knows)
Here's my thoughts http://investorshub.advfn.com/boards/read_msg.aspx?message_id=71889207
Another big criticism of Exelixis's development plan regarding Cabo. The big one is why didn't Exelixis pursue a Cabo vs Docetaxel trial? I think this is a valid criticism myself.