Assuming tapinarof earns FDA approval, he says, it will bring the first truly novel mechanism to the eczema and psoriasis
markets in quite some time.
LP0133/JTE-052 inhibits JAK 1-3 and tyrosine kinase (Tyk) 2. In a phase 2 AD trial, various concentrations yielded modified eczema area and severity index (mEASI) reductions between 41.7% and 72.9%, vs. 12.2% for placebo (P < 0.001 for all analyses).4
“Topical JAK inhibitors are going to be interesting because not only are we looking for efficacy in eczema and psoriasis, but those drugs might also get a lot of play in other dermatologic conditions such as alopecia areata and vitiligo, for which we lack an efficacious topical treatment outside of steroids. However, these conditions are also a little more diffi cult to design trials around, especially alopecia areata, which has a high rate of spontaneous recovery.”
One such medication, he adds, failed to meet primary endpoints due to high rates of treatment response in the vehicle treatment group.
Finding the right JAK inhibitor and formulating it into an effective topical vehicle has also proven challenging, he says, partly because some JAK inhibitors’ molecular heft is not ideal for topical application. Topical JAK inhibitors may debut in four to five years, Dr. Han estimates.
In AD, he adds, crisaborole ointment appears equivalent to a lower-mid-potency steroid.
“Some proportion of patients experience burning and stinging. I find that if you give crisaborole ointment to a patient who’s having a severe eczema flare who has already been scratching their skin, they’re the ones who are prone to burning and stinging.”
For such patients, he starts with a stronger topical steroid for two weeks.
Dr. Han has been an advisor for Intraderm, Janssen, UCB and Eli Lilly; an investigator for MC2 Therapeutics; a speaker for Sun Pharma; an investigator and speaker for Pfizer; and an advisor and speaker for Sanofi Regeneron.
George Han MD. “New and Upcoming Topicals in Psoriasis and Atopic Dermatitis,” Atlantic Dermatological Conference. May 5, 2019. New York.
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2. Smith SH, Jayawickreme C, Rickard DJ, et al. Tapinarof is a natural AhR agonist that resolves skin inflammation in mice and humans. J Invest Dermatol.2017;137:2110-2119.
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