...and the red-headed stepchild of regulatory acceptance.
In an earlier post, enabler wrote...
"Cabo.... ...... has remarkable and almost miraculous effects on bone metastasis in prostate cancer..."
Prove it. If the FDA will not acknowledge the acceptability of bone scan data, CTC reduction, BAP reduction nor other markers of bone turnover....nor will they acknowledge the suggestion by a world renowned research clinician that the Cabo bone phenomenon in mCRPC appears consistent with tumor necrosis...
What proof do you have? -some encouraging clinical response data and soe yet-to-be-explained pain relief from bone mets.
I've suggested this before, but I think we're waiting for the regulatory acceptance of some pertinent biomarkers sciences to catch up w/ Cabo.
Clinical response is everything. You can throw all the hypothetical science and preclinical results in the trash if clinical response in humans does not match. Cabo clinical results have exceeded all expectations, which is not all that unusual for breakthrough therapies. There was no way to predict current results based on existing knowledge. That's why clinical results are everything and why BigPharm continues to fail. Large corporations (similar to large government agencies) are dominated by conservative, cover-your-butt management that delay pulling the trigger - initiating clinical trials or approving drugs for new indications - until they "get it right". Meanwhile, biotechs are kicking the stuffing out of BigPharm and cancer patients do not have access to cabo because the FDA needs to "get it right."
"Meanwhile, biotechs are kicking the stuffing out of BigPharm and cancer patients do not have access to cabo because the FDA needs to "get it right."
Joe, in an earlier post, you made mention of off-label use...
I'm beginning to suspect a surprise in the 4/29 EXEL ER wrt off-label prescription...
Particularly due to the P2 RDT results published in last Nov's JCO.
Any thoughts to share on this....? Share the vision??
"I've suggested this before, but I think we're waiting for the regulatory acceptance of some pertinent biomarkers sciences to catch up w/ Cabo."
We are and it is a slow process, and franklly it should be slow and deliberate. Let's look at some of the counterarguments that have emerged over the past 2 years.
Hemoglobin-Cabo affects hemoglobin concentrations is an apparently positive way. The counterargument is that it now appears that Vegf therapies reduce overall blood volume. Increases in hemoglobin concentration may not reflect increased red blood cell production, but rather blood volume loss.
CTC reduction-It has also been suggested that VEGF therapy may not reduce CTC's but rather alters existing CTC surface marker presentation to render them less detectable to the CellSearch system approved by the FDA.
Bone markers (tALP) and Osteoclast (CTx) Activity-again very promising data, but just for grins, I would like to see Cabo's effect on these markers in patients lacking bone mets.
Don't get me wrong, I'm not questioning Cabo's efficacy, just the individual unproven methods used to demonstrate that efficacy. One of the problems DNDN is having marketing Provenge is that there is no clinical measure to show that the drug is "working." It is up to the patients and physicians to take it on faith that the treatment statistically prolongs survival. Bone scans are already an integral part of patient monitoring and treatment. Once approved, patients and doctors will want a treatment that improves pain and bone scans. So while the FDA may not have it built into its regulatory arsenal, those factors, BSR and pain improvement will make it a commercially successful drug once COMET 1&2 read out.
"So while the FDA may not have it built into its regulatory arsenal, those factors, BSR and pain improvement will make it a commercially successful drug once COMET 1&2 read out."
So without the encouraging ORR, RECIST response, and pain response we could easily postulate that - purely from the standpoint of regulatory perspective - Cabo is an interesting clinical compound that may be masking it's true clinical effects via a little-understood biologic version of "smoke & mirrors" . Compelling data, yet mysteriously little-understood mechanisms at play - perhaps even vaguely mistrusted due to it's uniquely broad-spectrum effect. Possibly even suspect of misdirected targeting of biologics. A form of clinical prestidigitation. Pharmaceutical abra-ca-dabra.
Thus the huge short crowd.
If it weren't for the stalwartly astute clinical following, I might be prone to agree.
Of course, I always was a sucker for magic tricks...
Unfortunately, there is no bone biopsy (not bone marrow biopsy) on lesion site for pathology evaluation in the study. Otherwise this will be most direct evidence for tumor necrosis or death.
Sentiment: Strong Buy