Replies to post #30672 on NorthWest Biotherapeutics Inc (NWBO)

[Dan88]

Again, useless debate and question which has long been solved:

Both overall survival and PFS are accepted endpoints for GBM by FDA. Such naive question had been the central point in the bashing of AF, and has been repeatedly refuted.

Some people just don't have enough!

[vator]

The SPA was not included because they would have required NWBO to stop the existing trial instead of leap frogging onto the next phase. Why all the old questions that have been hashed over the last year?

New people. Here we go again.

[Pyrrhonian]

If seeking full marketing approval yes, OS is the preferred choice. PFS is really a surrogate endpoint, though it has been the basis for full MA before. The main reason PFS is given weight is because it correlates with OS in many cases (but this is mixed). However, when seeking Accelerated Approval (which IMUC is not doing but NWBO is) then there is no need for a SPA, and a surrogate endpoint is acceptable. And if AA is granted, a follow up P4 must be embarked upon to establish clinical benefit (improvement in overall survival), though usually in a separate indication (lesser gliomas or rGBM would do). Meanwhile they can fully market and profit from the sale of the drug or biologic.

It gets a little complicated. Especially for Adam ;) But in short, NW's Ph III is a properly designed A&WC study whose results, if stat sig, will be used to petition regulators for Accelerated Approval.

[sentiment_stocks]

Hi Koman -

Wouldn't IMUC have to stick with an endpoint of OS for their P3 because that was their primary endpoint in their P2... and they haven't reached it yet?

I think if they'd waited longer and gone to the FDA after their OS data had had time to mature, they might have been able to get approval for a PFS primary end point.

NWBO has worked very closely with the FDA because it has an orphan drug designation. And the FDA regulations for that did not include the ability to convert a P2 trial to a P3 trial with a SPA (special protocol assessment) declaration.

So don't worry Koman, I'm sure the DCVax-L trial design is safe and in good hands. And while the competition for GBM patients may be getting fiercer, they'll soon have to go through L as the SOC. And soon after that (or maybe even at the same time), the improved version of L will have taken the current trial version of L's place.

Celldex and IMUC will both have to prove their treatments are more effective on their selected targets than L is when it's going after the same targets (and all the rest) to be approved. All we can do is make informed guesses on that right now. Germany and the UK have already guessed. I'm sticking with them.

[Astavakra]

You might recall, not long ago, maybe Nov/Dec, FDA approved bevacuzimab based on PFS with OS as a secondary.

[f3tt3f]

You can only apply for SPA after completion of phase 2 but pre-phase 3
Because we upgraded the PII trial to PIII, we couldn't apply for SPA based on the fact that there was no completion and, therefore, no unblinded data to discuss.