“From Injectable to Ingestible:” TYK2 Inhibitors for PsO and the Ongoing Challenge of PPP

“It seems that the anti-IL-23 peptide icotrokinra is more effective than the TYK2 inhibitors, but each one will have its advantage,” said Ron Vender, MD, in an interview with Dermatology Times at the 2025 Fall Clinical Dermatology Conference in Las Vegas, Nevada.

Vender, dermatologist, founder and director of Dermatrials Research Incorporated and Venderm Consulting Inc, associate clinical professor at McMaster University in the Department of Medicine, Division of Dermatology in Hamilton, Ontario, Canada, and an International Psoriasis Council Councilor, presented his insights into emerging TYK2 inhibitors for psoriasis and the continued need for advanced palmoplantar pustulosis (PPP) care.^1,2

The Rise of Oral TYK2 Inhibitors

According to Vender, psoriasis therapy is undergoing a transformation “from injectable to ingestible,” with TYK2 inhibitors emerging as one of the safest and most promising oral options. Although TYK2 belongs to the JAK family, its mechanism is distinct, resulting in a more favorable safety profile compared with traditional JAK inhibitors.

Currently, deucravacitinib is the only FDA-approved TYK2 inhibitor, demonstrating biologic-like efficacy for moderate to severe plaque psoriasis. Additional TYK2 inhibitors—zasocitinib (formerly TAK-279) and envudeucitinib (formerly ESK-001)—are in advanced clinical development. “We’re seeing great efficacy from this class, mimicking biologics such as ustekinumab,” Vender explained, noting their particular appeal for patients who prefer oral dosing or have injection aversion.

Beyond TYK2 inhibition, extended half-life biologics are also on the horizon. Vender referenced ongoing studies of an extended half-life risankizumab (ORCA molecule) that could eventually allow dosing just once or twice annually, as well as emerging anti–IL-17 agents engineered for similarly prolonged activity.

Palmoplantar Pustulosis: An Unmet Need

Vender highlighted PPP as one of the most difficult psoriasis subtypes to manage. Though related to plaque psoriasis, PPP presents a unique pathophysiology involving Koebnerization, pustulation, and barrier penetration challenges in the palms and soles. “There’s nothing that really works well,” he said, emphasizing the refractory nature of the disease.

While various biologics have shown moderate efficacy, investigational efforts are ongoing, including a bimekizumab trial specifically targeting PPP and exploratory work with topical JAK inhibitors. Among currently available options, Vender pointed to apremilast (PDE4 inhibitor) as his first-line systemic choice for PPP due to its favorable safety profile and consistent efficacy observed in practice and studies.

Oral Therapeutics and Patient Preferences

Injectable biologics offer long dosing intervals, but for many patients already taking daily medications for comorbidities, adding an oral psoriasis agent is convenient. Vender contrasted daily zasocitinib (not food-sensitive) with icotrokinra, an anti–IL-23 peptide receptor modulator requiring fasting administration. Although early data suggest greater efficacy with anti–IL-23 approaches, TYK2 inhibitors remain attractive for their safety and accessibility.

Ultimately, Vender concluded, “Palmoplantar pustulosis remains the biggest unmet need in psoriasis,” underscoring the importance of continued innovation across both oral and biologic modalities.

References

1. Armstrong A, Strober B, Vender R. Setting sights higher with new and emerging TYK2 inhibitors for psoriasis. Presented at: 2025 Fall Clinical Dermatology Conference; October 23-26, 2025; Las Vegas, NV.
2. Lebwohl M, Vender R. Diagnosing and treating palmoplantar pustulosis. Presented at: 2025 Fall Clinical Dermatology Conference; October 23-26, 2025; Las Vegas, NV.