Replies to post #178265 on Biotech Values

[DewDiligence]

ISIS—Does 100mg difference—300 vs 200—really make 7-fold difference in efficacy?

Highly implausible, IMO; hence, the results in one of the two ISIS-FXIRx trial arms were presumably a fluke.

[iwfal]

ISIS -

Does 100mg difference - 300 vs 200 - really make 7-fold difference in efficacy? I doubt it unless there is another dose level for reference.

I agree that it is probable that upon repeat the difference will not be that great. On such splits it is typical for a repeat of the test to come closer to splitting the difference - and even a 3 fold reduction in VTE rate would be very good.

That said, it is not entirely implausible that there are "non-linear" effects - especially in comparison to an Enox baseline. E.g.:

1) No drug: VTE rate is (WAG) 90%.

2) 200mg (same as enox): DVE rate is (WAG) 21% (~1/4 of no drug)

3) 300mg: DVE rate is (WAG) 3%. (1/7th of 200 mg)

Some non-linearity - but not anywhere near as dramatic as "no effect for 200mg vs 1/7th for 300mg" sounds.