Arcutis scraps topical JAK phase 2 over drug delivery concerns

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Arcutis plans to reenter the clinic with a reformulated vitiligo candidate. (Markus Spiske)

Arcutis Biotherapeutics has terminated a phase 2a clinical trial of its vitiligo candidate over concerns the topical formulation will fail to get enough active drug to targets in the skin.

California-based Arcutis started the 500-subject study of topical JAK1 inhibitor ARQ-252 in March. Two months later, the company revealed a phase 2 study of ARQ-252 in chronic hand eczema failed. None of the ARQ-252 arms were statistically better than control. Having analyzed results from the failed study, Arcutis has determined the implications for the vitiligo trial are negative.

Rather than wait for top-line data in the second half of 2023, Arcutis has chosen to kill the vitiligo trial in its infancy. The action is underpinned by evidence the eczema study failed because of inadequate local drug delivery to the skin.

After completing the analysis, Arcutis continues to believe topical JAK inhibitors could work in vitiligo and chronic hand eczema, pointing to data on rival candidates and the oral version of ARQ-252 to make its case. The problem, as Arcutis sees it, is the delivery vehicle. Work is underway to solve that problem. 

“We have already made good progress in reformulating ARQ-252 to potentially deliver much more active drug to targets in the skin and hope to re-enter the clinic with this reformulated version in the not-too-distant future,” Patrick Burnett, M.D., Ph.D., chief medical officer at Arcutis, said in a statement.  

The delay could be detrimental to Arcutis in the competitive topical JAK space. Incyte is set to learn whether the FDA will approve its topical ruxolitinib formulation in atopic dermatitis in September, three months later than originally planned, and Leo Pharma recently began a phase 3 trial in chronic hand eczema. Aclaris Therapeutics also recently brought its prospect through a midphase study.