Innovation Pharmaceuticals Inc (IPIX)

[PlentyParanoid]

A little warning about those PGA 0/1 and PASI75 values people are throwing at each other.

The widely used efficacy measure PGA 0/1 response is generally defined as
PGA SCORE 0 or 1 WITH AT LEAST 2 POINT REDUCTION IN PGA SCORE.

Very often the above is reported as PGA score 0 or 1, because the trial population is composed of subjects having PGA 3 or higher ie. the 2 point drop is given if a subject scores PGA 0 or 1. It is dangerous to forget that.

Example: Can-Fite reported 2 mg dose of CF101 scoring 23.5 % PGA 0/1 response in p2 and hurried into p3, where the PGA 0/1 response was whopping 6.2 %. Can-Fite had included PGA 2 (and 1) subjects in p2 trial. 3 out of 4 PGA 0/1 achievers were PGA 2 at baseline and went to PGA 1 by week 12. This is obvious if you study Can-Fite's generous explanation of PASI50 score for the only 4 subjects that reasched it: values 47.7, 49.9 (what were these doing in PASI50?), 73, and 90 %. Only one of those can possibly be PGA 0/1. THE REAL PGA 0/1 in p2 was 5.9 %, very consistent with p3 results and disastrous for Can-Fite.

IPIX reports that at week 12 prurisol 200 mg ITT group had PGA 0/1 response of 42.8% and PP group had response of 55 %. They did, but not PGA 0/1 with at least 2 point reduction. Both ITT and PP groups included PGA 2 subjects, some of which DID score PGA 0 or 1 at 12 weeks. THE PROPER NUMBERS for PGA 0/1 response (with 2 point reduction) are:

Prurisol PGA 0/1 response: ITT 25 %, PP 35 % at 12 weeks. PGA 0/1 response for 19 subjects with baseline PGA equal to 3: 31.6 % at 12 weeks.

BTW: that 12 weeks is important to note if you compare with Otezla. Most Otezla trials used 16 weeks treatment period and Otezla's PGA 0/1 and PASI75 scores tend to rise between 3 to 5 percentage points from week 12 to 16.

Useful examples for Otezla:
Otezla trial having only PGA 3 subjects, headcount 148, dosing 30 mg BID PGA 0/1 response at 16 weeks: 30.4 %.
If you compare this to PGA 0/1 response of 31.6 % for Prurisol 200 mg PGA=3 subjects you are giving Otezla some advantages:
1. Longer treatment period for Otezla is responsible for 3 to 5 percentage points
2. 30 mg BID is maximum approved dose for Otezla, if all goes well 200 mg for prurisol will not be. Probably 400 mg (200 mg BID).

Let's compare Otezla 20 mg BID to prurisol 200 mg (100 mg BID). There is just one Otezla trial with 20 mg BID dose and published PGA 0/1 response. Otezla p2 trial for 87 subjects with PGA at least 3 had PGA 0/1 response of 28.7 % at week 16. Remember: even here Otezla has the advantage of 16 weeks treatment time.

In 3 clinical trials with Otezla dose 20 mg BID I have found PASI75 responses are: 30 % at 12 weeks, 24.4 % at 12 weeks and 28.7 at 16 weeks. My psoriasis spreadsheet has currently about 60 trials with over 110 reported PASI75 and PGA 0/1 response pairs; 80 % have PGA 0/1 to PASI75 response ratio below 1.0. The mean value for the ratio is 0.89. Conclusion: comparing PASI75 response to PGA 0/1 response probably favors PASI75.