Ann: PAR Reports Phase 3 Clinical Trial Update, page-26

Your concerns are justified. We have shown time and again that 2mg/kg twice weekly works, so why did PAR not trial it alongside 1.5mg/kg twice weekly? It is likely that 2mg/kg once weekly does not work based on the 008 results and that the other dosing regimes do not work also, so it seems our hope rests solely with 1.5mg/kg twice weekly.

My guess is that the DMC are tasked with ensuring the 1.5 x 2 dose will achieve clinically meaningful results by the completion of the 002 and 003 trials, since they will not want ~2000 patients to continue receiving a treatment dose that is ineffective. That is, they will not only consider the primary endpoint but key secondary endpoints when selecting the dose. I'm not sure if we have to pay a type I penalty to allow the DMC to look at these endpoints though.

So my guess is that if the DMC agree to the 002 to progress to stage 2 without modification then they must see some signals in the data that support it. On the other hand, it is possible the DMC may not allow progression to stage 2 and instead request modifications, in which case PAR may be able to go to the FDA about increasing the dosage to 2mg/kg.

I hope PAR are planning for these contingencies with all the time they seemingly have on their hands.

My views only, dyor