Small Molecules

An Overview of Emerging Therapeutic Options in the Treatment of Psoriasis

Melinda Gooderham, MD, MSc, FRCPC

Disclosures

Skin Therapy Letter. 2013;18(7) 

In This Article

ASP015K

ASP015K (Janssen, previously Astellas) is another oral JAK inhibitor that has shown selectivity of JAK1/JAK3 over JAK2 in cell-based assays. A Phase 2a randomized, placebo-controlled, sequential dose-escalation study of 10 mg, 25 mg, 60 mg, 100 mg BID or 50 mg OD was carried out over 6 weeks in patients with moderate to severe psoriasis. ASP015K demonstrated efficacy with dose-dependent reductions in body surface area (BSA) and mean PASI and Psoriasis Static Global Assessment (PSGA), and was generally well-tolerated.[11] Janssen acquired ASP015K in October 2012, and there are no current plans to develop this drug in a psoriasis platform.

Topical JAK Inhibitors

In contrast to other biologics, due to their small size, these agents have also been demonstrated to be of benefit when applied topically. Topical tofacitinib has been studied (ClinicalTrials.gov, identifier NCT00678561) on 81 patients with OD or BID application of 0.02%, 0.2% and 2% ointment compared to vehicle for 28 days, although results are not yet published. A Phase 2b trial of topical tofacitinib comparing two dose strengths and two dose regimens is currently underway (ClinicalTrials.gov, identifier NCT01831466).

Ruxolitinib, the first US FDA-approved selective JAK1/JAK2 drug used orally for myelofibrosis,[3] has also been investigated in its topical form (INCB018424, Incyte) for use in psoriasis. A Phase 2a trial comparing topical INCB018424 0.5%, 1% and 1.5% cream in a double-blind, vehicle-controlled fashion was shown to be safe and effective with improvement in total lesion score, PGA and PASI.[12,13] This study compared topical INCB018424 with currently approved topical therapies, calcipotriene 0.005% cream and betamethasone diproprionate 0.05% cream[13] (ClinicalTrials.gov, identifier NCT00820950).

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