Oral tyrosine kinase 2 inhibitor PF-06826647 demonstrates efficacy and an acceptable safety profile in participants with moderate-to-severe plaque psoriasis in a phase 2b, randomized, double-blind, placebo-controlled study

Abstract

Background: Psoriasis treatments lack durable efficacy and have inconvenient administration, highlighting the need for new therapies.

Objective: To evaluate the efficacy and safety of tyrosine kinase 2 inhibitor, PF-06826647, in moderate-to-severe plaque psoriasis.

Methods: This phase 2b, double-blind study randomized participants to oral, once-daily PF-06826647 (1:1:2:2:2) 50:100:200:400 mg:placebo (16 weeks), then 200 or 400 mg (24 weeks) (NCT03895372). The primary end point was a proportion of participants achieving psoriasis area severity index (PASI) 90 at week 16. Secondary end points (PASI50/75/90/100; Physician's Global Assessment) and safety were assessed to week 40.

Results: Overall, 178 participants were treated. A significantly greater proportion of participants (risk difference % [90% CI]) achieved PASI90 in the 200-mg (33.0 [18.0, 47.1], P = .0004) and 400-mg (46.5 [30.6, 60.6], P < .0001; week 16) groups versus placebo. Significant increases from placebo were observed for all secondary end points (200 and 400 mg; weeks 6-16; P < .05); increases were evident to week 40 (categorical data). PF-06826647 was well tolerated and most treatment-emergent adverse events were mild/moderate. Eighteen participants discontinued due to treatment-emergent adverse events (14 arising from laboratory abnormalities).

Limitations: Limitations included the large proportion of White males and non-placebo-controlled extension.

Conclusion: PF-06826647 200 and 400 mg once daily showed significant efficacy versus placebo at week 16 and was well tolerated over 40 weeks.

Keywords: TYK2 inhibitor; clinical trial; efficacy; phase 2b; placebo-controlled; psoriasis.