Oral TYK2 inhibitor shows promise in plaque psoriasis

A phase 2 trial found the oral tyrosine kinase 2 inhibitor PF-06826647 to be safe and efficacious in the treatment of moderate to severe plaque psoriasis.

“Tyrosine kinase 2 (TYK2) belongs to the Janus kinase (JAK) family of intracellular kinases that play a role in cytokine signaling and inflammatory diseases,” Christopher Tehlirian, MD, MBA, and colleagues wrote.

This phase 2b randomized, double blind, placebo controlled parallel group study included 178 subjects randomly assigned 1:1:2:2:2 to receive once daily PF-06826647 50 mg, 100 mg, 200 mg or 400 mg or placebo for 16 weeks, followed by PF-06826647 200 mg or 400 mg for 24 weeks.

At week 16, PASI90 was reported in a greater proportion of patients treated with PF-06826647 200 mg (risk difference, 33%; 90% CI, 18%-47.1%) and 400 mg (risk difference, 46.5%; 90% CI, 30.6%-60.6%) compared with placebo, with differences becoming noticeable by week 4.

All treatment groups had a numerically greater proportion of patients achieving PASI90 from weeks 6 to 16 compared with placebo.

Similar results were seen for PASI50, PASI75 and PASI100, with all but the 100 mg treatment groups having numerically greater proportions achieving the endpoints compared with placebo.

The 200 mg and 400 mg treatment groups showed significant differences from placebo for all secondary endpoints including Physician Global Assessment response and Peak Pruritus Numerical Scale score.

Treatment-emergent adverse events were mostly mild or moderate. The most common were nasopharyngitis, upper respiratory tract infection and increased blood pressure. Seven patients experienced severe treatment-emergent adverse events, with three considered treatment-related.

“The selective, oral TYK2 inhibitor, PF-06826647, at 200 mg and 400 mg [once daily] showed significant efficacy versus placebo at week 16 and was well tolerated over 40 weeks in participants with moderate to severe psoriasis,” the authors wrote.