Biotech Values

[poorgradstudent]

re: ONXX

I think the dexamethasone issue is a red herring. There is a reason why dexamethasone treatment is dosed significantly higher than the small dose that was allowed to be administered to ameliorate the side effects at the time of carfilzomib administration. The concentration is nowhere near therapeutic, unless you have data suggesting otherwise.

As for the tolerability of velcade: if you bring the safety aspect of velcade into it, then you need to acknowledge the efficacy. In this respect, carfilzomib has undeniable activity in those resistant or intolerant to Velcade, which is an unmet need in my book. Also, the improved tolerability of SubQ velcade only applies to the neuropathy... there is no indication that the cardiac events were reduced, which are the salient side effects in play. In that respect, a reference to SubQ Velcade isn't one that makes carfilzomib look worse. The velcade PI has all the same warnings that the FDA was ok with when they gave it accelerated approval.

The protocol violations are disappointing. Most of these appear to be due to patient compliance, which the company needs to take seriously. In a trial of patients who have exhausted most of their treatment options, however, I'm not so outraged by an enrollment error where they missed inclusion / exclusion criteria. It's not like these people don't have myeloma, and it's clear that their previous history was accurately reported (and confirmed) by the FDA. I think this is your most valid point, however. Protocol violations are just poor form.

As to the FDA regulation you copied, I don't really understand the point. The passage is intentionally vague and could be interpreted either way. Are you suggesting that this trial did not test the "safety and effectiveness" of "treating serious or life-threatening illnesses" and that carfilzomib was tested for its ability to provide "therapeutic benefit to patients who are ... unresponsive to, or intolerant of, available therapy?" Even the FDA acknowledges with their efficacy analysis that the response to carfilzomib was independent of the number and type of previous regimen...

I also think point #4 exemplifies the mission creep into the accelerated approval process. If the FDA wants randomized trials for accelerated approval, then we should probably just remove the accelerated approval pathway.


I agree that they won't approve. But I don't think your comments are all that convincing considering the pathway that Velcade followed to approval. It seems to me that you would have been equally disappointed with Velcade's initial NDA application, because it was essentially identical to this carfilzomib application. I guess where you see a poorly run single arm phase 2 trial, I see a trial that is following in the footsteps of a very successful example of accelerated approval.