The Show Must Go On

An Update on Clinical Experiences and Clinical Studies on Novel Pharmaceutical Developments for the Treatment of Atopic Dermatitis

Tatjana Honstein; Thomas Werfel

Disclosures

Curr Opin Allergy Clin Immunol. 2020;20(4):386-394. 

In This Article

Targeting the Histamine 4 Receptor With Adriforant for the Treatment of Atopic Dermatitis

The histamine (H)-4 receptor is expressed not only on afferent (sensitive) nerve fibers but also on many inflammatory cells. Therefore, its blockade promises a dual mechanism of action: direct decrease of itching and reduction of inflammatory activity. In a number of in-vitro models, a function of the H4-receptor in Th2-polarized and also in Th-17 inflammation was shown suggesting that the receptor might be a therapeutical target structure in atopic dermatitis and possibly also in psoriasis.[38] In an in-vivo murine model of atopic dermatitis (ovalbumin-induced eczema by epicutaneous sensitization in wild-type versus H4 receptor knock out mice), it was shown that in the absence of the H4-receptor eczema reactions were significantly weaker in the knock-out model. Moreover, an antagonist against the H4-receptor was able to suppress skin reactions in the mouse model in vivo.[38]

A first proof-of concept study in humans with atopic dermatitis with the H4-receptor antagonist JNJ-39758979 had to be stopped and unblinded for safety reasons (two cases of severe neutropenia). Numerical improvements in median EASI and itch scores were observed with the study drug at week 6, although the primary endpoint was not met probably to premature study discontinuation.[39]

In a phase IIa proof-of-concept study on 98 patients with atopic dermatitis with the orally administered, high-affinity H4 receptor antagonist adriforant (ZPL3893787), significant effects on the visible lesions of eczema with a 50% reduction in EASI were seen, with lower effects on itching. Side effects, especially on neutrophils or other cells in blood counts, did not occur with this compound.[40] The principle of H4-receptor blockade is a promising approach that is now investigated in larger phase IIb study with adriforant.

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