Innovation Pharmaceuticals Inc (IPIX)

[KMBJN]

Flash quoted this article about anti-IL20 helping treat psoriasis:

http://www.ncbi.nlm.nih.gov/m/pubmed/18945296/

and GeorgeIJ has been adamant that Prurisol would be good for every disease involving IL-20 as part of its pathogenesis, so I thought I would look to see if any anti-IL-20 antibodies have been developed and how well they worked.

I ran across the Phase I study testing fletikumab/anti-IL-20 against psoriasis:

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0134703

They were referring to Flash's study in the quote I gave, that anti-IL-20 antibody worked in the mouse SCID model, but did not work in humans, calling into question the predictive validity of the model.

"Summary

Background Interleukin (IL)-20 is a recently discovered cytokine displaying increased levels in psoriatic lesions. Interestingly, IL-20 levels decrease with antipsoriatic treatment, correlating with clinical improvement. However, the role of IL-20 in the aetiology of psoriasis is unknown.

Objectives In this study, we investigate the effects both of blocking IL-20 signalling in psoriatic plaques and of adding IL-20 to nonlesional psoriasis skin.

Methods We employed the human skin xenograft transplantation model in which psoriatic plaques and nonlesional keratome skin biopsies obtained from donors with moderate to severe plaque psoriasis were transplanted on to immuno-deficient mice. The transplanted mice were treated with anti-IL-20 antibodies or recombinant human IL-20.

Results We demonstrate that blocking IL-20 signalling with anti-IL-20 antibodies induces psoriasis resolution and inhibits psoriasis induction. We also demonstrate that continuous IL-20 infusion, together with injection of additional nonactivated leucocytes, promotes induction of psoriasis in nonlesional skin from patients with psoriasis.

Conclusions The results suggest that IL-20 plays a critical role in the induction and maintenance of psoriasis, and IL-20 is suggested as a new possible specific target in psoriasis treatment."

So, success in the mouse SCID model of psoriasis (inducing psoriasis resolution and preventing induction) did NOT translate into human success for that particular drug.

"The severity of psoriatic lesions in the grafts was assessed twice weekly in a blinded fashion and scored semiquantitatively according to the clinical signs: scaliness, induration and erythema. The parameters were scored using a four-point scale: 0, complete lack of cutaneous involvement; 1, slight involvement; 2, moderate involvement; 3, severe involvement."

" Interestingly, treatment with anti-IL-20 pAb or mAb promoted a resolution comparable with the effect of ciclosporin and reduced the semiquantitative clinical psoriasis score by 1·5 ± 0·1 (anti-IL-20 pAb, mean ± SEM, P = 0·01) and 1·1 ± 0·5 (anti-IL-20 mAb, mean ± SEM, P = 0·06), respectively, as compared with their respective negative controls (Fig. 3a and data not shown). "

You said that "Looking at a safety and tolerability trial that lead to abandoning fletikumab for psoriasis in order to glean some kind of insight into Prurisol (Abacavir) is a waste of time."

When the same model of psoriasis failed to predict response in humans to another drug, IMO, perhaps we shouldn't have quite as much confidence that the model will predict success in humans with our drug, Prurisol.

I'm hoping P will be successful, but the mouse SCID model isn't perfect in translating results to humans.