Novel TYK2 Inhibitor Shows Promising Results in Phase 2 Trials for PsO

The TYK2 inhibitor ESK-001 has shown promising safety and efficacy in long-term Phase 2 trials for moderate-to-severe plaque psoriasis, Andrew Blauvelt, MD, FAAD, said in a late-breaking research presentation at the 2025 American Academy of Dermatology (AAD) Annual Meeting in Orlando, Florida.

“The majority of patients improved from Week 12 to Week 52, [which is] what you would expect with this kind of mechanism of action,” Dr. Blauvelt said. “We also have excellent data in terms of quality of life and itch.”

During “Efficacy and Safety of ESK-001, a highly effective selective oral TYK2 inhibitor, in moderate-to-severe plaque psoriasis: long term Phase 2 results,” Dr. Blauvelt reported that approximately 40% of patients achieved PASI 100, approximately 60% reached PASI 90, and approximately 80% hit PASI 75 through 52 weeks on ESK-001. Efficacy also improved over time.

“You see the responses gradually increasing, which also is consistent with the inhibition of IL-23,” he said. “We know drugs that inhibit IL-23 tend to keep working over time, usually peaking around 6 months’ time, and that's what we saw here.”

The drug, he said, was designed to be different from classic JAK inhibitors.

“The whole goal is to try to avoid inhibition of JAK1, 2, and 3 to avoid the side effects that we see in classic JAK inhibitors,” he said. “So ESK-001 was designed in that manner to avoid the classic JAK inhibition. Another important thing is to optimize the inhibition of this target.”

While multiple dosing strategies were tested initially, the investigators determined that 40 mg twice daily is optimal.

ESK-001 is now undergoing Phase 3 testing as part of the ONWARD study, with more than 600 patients currently enrolled, Dr. Blauvelt said.