Beyond Sotyktu: Next-Gen TYK2 Drugs Enter Late-Stage Development | Fall Clinical Derm 2025

When Sotyktu (deucravacitinib) was approved in 2022 it was seen as a major milestone in the treatment of psoriasis. It was the first oral medication that inhibits tyrosine kinase 2 (TYK2), an enzyme that is involved in the inflammatory and immune response. Developed by Bristol Myers Squibb, Sotyku is used to treat patients with moderate-to-severe plaque psoriasis. It still is the only one in its class.

Psoriasis is a chronic, systemic, immune-mediated disease that affects about 7.5 million people in the United States. Nearly one-quarter of people with psoriasis have cases that are considered moderate-to-severe.

Now several therapies are in late-stage development, and dermatologists at the 2025 Fall Clinical Dermatology Conference in Las Vegas are expressing excitement at the possibility of having other options for patients.

One drug in late-stage development is brepocitinib, an oral drug that inhibits both TYK2 and JAK1, another enzyme that is also involved in the inflammatory and immune response. Brepocitinib’s developers, Roivant and Priovant Therapeutics, recently released data from a phase 3 trial that is assessing brepocitinib as a treatment for patients with dermatomyositis (DM), an autoimmune disease that causes debilitating muscle weakness and skin lesions. Dermatomyositis rashes often affect large portions of a patient’s body including the scalp and are often disfiguring and painful. No targeted therapies are approved, and a majority of patients require high-dose chronic oral corticosteroids.

In the VALOR trial, brepocitinib 30 mg demonstrated clinically meaningful and statistically significant improvement compared with placebo on the total improvement score (TIS), the primary endpoint. TIS is a composite score that measures improvement in dermatomyositis or polymyositis.

Priovant intends to file a new drug application (NDA) in early 2026.

Another TYK2 in phase 3 development is envudeucitinib, which is being developed by Alumis. The company has completed enrollment in the pivotal phase 3 ONWARD clinical program. This consists of two phase 3 placebo-controlled 24-week clinical trials, ONWARD1 and ONWARD2, designed to evaluate the efficacy and safety of envudeucitinib in adult patients with moderate-to-severe plaque psoriasis. Topline data from these trials are expected in the first quarter of 2026.

ONWARD3, an optional long-term extension trial for patients who have completed week 24, is ongoing.

In an interview with Dermatology Times, a sister publication of Managed Healthcare Executive, Benjamin Lockshin, M.D., assistant professor of dermatology at Georgetown University, discusses how TYK2 inhibitors have changed the management of patients with psoriasis. Lockshin is also executive vice president of strategic Initiatives and director of the clinical trials center at US Dermatology Partners.

Q: How have TYK2 inhibitors changed the treatment landscape for psoriasis?

A: TYK2 inhibitors have really changed the landscape in terms of our management of patients with psoriasis for moderate and severe patients that are looking for an oral option. TYK2 inhibitors such as deucravacitinib, have allowed us to have meaningful response rates for psoriasis vulgaris, as well as in tough-to-treat areas like the scalp, palms and soles.

Deucravacitinib is ideal for moderate patients and patients who are younger. The younger patient in their late teens, early 20s, with moderate to severe psoriasis may have no issue incorporating just one other pill into their routine. Many patients don’t want the hassle of having an injection, especially if they’re living in a group house or in a college dorm. They may not want that injectable in your fridge.

TYK2 inhibitors hit that sweet spot in terms of managing patients’ disease. It’s a good complement to our treatment options that include biologics. Biologic efficacy outperforms oral agents in general, but certainly individual responses, especially in that moderate category, are very good in achieving high levels of clearance with a medication like deucravacitinib.

Q: What therapies in development for psoriasis are you excited about?

A: It’s an exciting time to manage patients with psoriasis, given the multiple different MOAs [mechanisms of action] and especially the introduction of a few new oral options. The new second generation TYK2 inhibitors may afford us higher levels of skin clearance and also add to the meaningful safety data that we see with deucravacitinib.

Related: Icotrokinra Demonstrates High Clearance Rates in Plaque Psoriasis | Fall Clinical Derm 2025

Moreover, the IL-23 peptide icotrokinra will offer us an opportunity to achieve high levels of skin clearance that we’re only seeing with biologics with an oral product. In addition, we’re able to capitalize on the safety data that we see with IL-23 inhibitors with an oral product.

I’m excited about the introduction of multiple different therapeutic options for inflammatory conditions in 2026. What’s especially interesting to me are these new oral options and potentially the introduction of biologic agents with extremely long half-lives that will allow patients to maintain disease free periods with perhaps one or two shots a year.