Phase II trial of selective tyrosine kinase 2 inhibition in psoriasis

Tyrosine kinase 2 (TYK2) signaling pathways are suspected in the pathophysiology of psoriasis, prompting researchers to try blocking them as a way to treat the skin condition. They designed a Phase II trial of oral BMS-986165, a selective inhibitor of TYK2, and enrolled 267 participants with moderate to severe disease.

Tyrosine kinase 2 (TYK2) signaling pathways are suspected in the pathophysiology of psoriasis, prompting researchers to try blocking them as a way to treat the skin condition. They designed a Phase II trial of oral BMS-986165, a selective inhibitor of TYK2, and enrolled 267 participants with moderate to severe disease. Patients were randomly allocated in groups of 44 or 45 to several treatment arms. The main outcome was at least a 75% lower Psoriasis Area and Severity Index (PASI) score at week 12, representing a meaningful reduction in disease severity. That endpoint was achieved in 7% of the controls. The share rose to 9% for patients who took 3 mg of BMS-986165 every other day, to 39% for patients who took 3 mg daily, to 69% for patients who took 3 mg twice daily. The percentage dropped slightly to 67% among patients on a twice-daily dose of 6 mg, but soared to 75% with a daily dose of 12 mg. The findings indicate BMS-986165 works better than placebo to clear psoriasis over 12 weeks. Although there were only three serious adverse events in patients receiving the active drug, plus one case of malignant melanoma 96 days after the start of treatment, researchers agree that more research is needed to confirm safety and lasting effect.