A fuzzy prurisol prediction based on really fuzzy math.
Assumed:
1. The IGA 0/1 percentage from p2a trial is not stable, but the 'true value' is somewhere between current 6 plus minus 2 (or plus minus 33 %) out of 19. That is 4/19 and 8/19 or 21 % and 42 %.
2. The ratio of PASI 75 to IGA 0/1 is equal to the worst I could found in apremilast trials. That is 0.71, ie. the bottom of the range from 0.71 to 1.53. This is a conservative assumption.
Scenarios:
A. No changes in effectiveness when dose goes from 200 mg to 300 mg
B. Change of effectiveness from 200 mg to 300 mg similar to apremilast's change in p2 trial from 20 mg BID to 30 mg BID. That is 42 % increase.
Resulting PASI 75 ranges for prurisol 2b trial:
pessimistic one: 15 to 30 %
optimistic one: 21 to 42 %
Probability of success:
If we assume that approval threshold is PASI 75 at or over 25 % plus uniform distribution of outcome percentages then chances of success are
pessimistic: 100*(30 - 25)/(30-15) = 33.3 %
optimistic: 100*(42 - 25)/(42 - 21) = 81.0 %
average chances = 57 %, and that is based on some rather guarded assumptions.
I put this up in order to remind some of us that if you envision worse or better outcome you will be assuming factors that are hard to justify based on the data at hand or outright denying any value for available data. Enjoy or get enraged.
PS: Among other things ignored I did not consider what happens when trial population changes from mild to moderate to moderate to severe. So, yes, there is an out clause with my conclusions.
PPS: Why 300 mg and not 400 mg? My guess based on the trial randomization of 3:1:3 for 300 mg: 400 mg: placebo that IPIX is aiming at 300 mg dose.
