SLCImmuno post elsewhere:
slcimmuno Member Level Sunday, 06/18/17 12:55:44 PM
Re: biodoc post# 186322
Post # of 186356
Thx for comments biodoc - always appreciated.
Agree: The Otezla efficacy bar -- around 30% PASI 75 -- is the one we're hoping to meet... or beat... plus in a shorter timeframe, 12 weeks instead of 16 weeks.
The PASI 90s, even PASI 100s, though, will be worth watching. IGA 1/0 (almost clear / clear) is closer to PASI 90 than PASI 75. See cites below, with the first article particularly insightful, great aggregate data on the Anti-TNFs and IL-17s.
Have to say Biologics are impressive in PsO unlike IBD - strong PASI 90s and better, and quick on uptake..... in a recent study, half of Cosentyx patient achieved PASI 75 at Week 4 vs. 20% of patients on Stelara. But biologics come w baggage ... costly... tens of thousands of dollars, response failures [30%], effect wanes over time [30%] and side effects.
That in the Ph2 P trial (admittedly small) 46% of the IGA 3s (moderate) saw at least a 2-pt drop suggests healthy PASI 90s might be in the offing, particularly with jump from 200mg to 300mg and 400mg. Severe PsO patients might even respond better. If we crush Otezla in almost/clearing PsO and encroach on some of the lower end biologics (Cosyntex a reach), watch out. Also am interested in seeing if the 300mg and 400mg suggests dosing could go even higher -- i.e. up to the 600mg Ziagen I think maxed out at.
I think the Interim is being done to whet appetites of interested parties. If Prurisol shows it is fast on the draw (maybe 20-25% PASI 75 by week 4 - 6... almost as good as the likes of Stelara) that will be a strong signal. The slope steep and yet to plateau. For comparison, it looks like Otezla had about 5% PASI 75 at week 4 and maybe 12% at week 6. I also assume IPIX will comment on efficacy trends in patients who've been on treatment longer than 6 weeks.
See Figure 4
Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: Results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1)
Hopeful we see 40-50% PASI 75s over 12 weeks, with healthy PASI 90s... again Otezla only 8% PASI 90 over 16 weeks. If P can be shown to equal or better Otezla in less time, perhaps even while suboptimally-dosed, then we've def gotta a Big Winner. If it gets into the biologics space, then we've got a Humongous Winner.
Treatment goals for psoriasis: Should PASI 90 become the standard of care?
"a PASI 75 response would associate to an absolute PASI around 5, compatible with a PGA score of 2, usually considered mild psoriasis (mild plaque elevation, light red coloration, predomination of fine scale). However PASI 90 response would equate to a PASI around 2, compatible with a PGA of 0/1 (almost clear).In this sense, PASI 90 response probably better reflects a “clear”/“almost clear” status than PASI 75."
The 5-point Investigator's Global Assessment (IGA) Scale: A modified tool for evaluating plaque psoriasis severity in clinical trials.
Whereas IGA/PGA 0/1 responder rates for earlier scales are strongly associated with PASI 75, the IGA 0/1 rate for the secukinumab 6-point scale was more robust, demonstrating a strong association with PASI 90, and the results for the 5-point IGA are expected to show the same association.