The evolving understanding of psoriasis has highlighted the need for additional targeted therapeutic agents. This has prompted ongoing research and clinical trials focused on biologics and new-generation oral small molecules, aiming to provide more effective and accessible treatment options for patients with psoriatic disease. Some of these emerging agents were discussed at the recent Maui Derm Hawaii 2025 meeting.

Following these presentations, featured expert Jason Ezra Hawkes, MD, MS, FAAD, was interviewed by Conference Reporter Associate Editor-in-Chief Rick Davis. Clinical perspectives from Dr Hawkes on these findings are presented here.

Our understanding of the pathogenesis of psoriasis has come a long way, from the time when we were using broad-acting oral immunosuppressants to when we began developing more targeted agents that help suppress the predominant pathways driving psoriasis. Biologics have set the standard for how we care for patients with both plaque psoriasis and psoriatic arthritis. However, there has been a lag in the development of newer oral agents, and this has created a treatment opportunity for addressing patient preferences. Patients with psoriasis who are looking to achieve the highest rates of clearance have been forced to choose between biologic therapies and some of the oral small molecules, the latter of which have been appealing to patients but have not historically reached the same clinical efficacy end points.

Over the last 5 years, we have seen the development of newer biologic therapies that are even more targeted or have novel mechanisms of action compared with older biologics. We have also seen a dramatic improvement in the new oral therapies that are coming out for psoriatic disease. This includes agents evaluating unique targets such as TYK2, which is central to IL-23 cytokine signaling. We have also seen trials of oral therapies that can hit new targets, such as the investigational oral IL-23 receptor inhibitor JNJ-77242113. Additionally, the phase 2 clinical trial data for the novel IL-23 receptor inhibitor suggests that this exciting oral therapy can result in complete skin clearance in approximately 40% of patients. These developments will significantly increase our oral therapy options and will hopefully help close the gap between oral agents and biologic therapies, leveling the playing field regarding efficacy for those who may prefer a pill over an injection.

Durability of treatment response with oral therapies is also important to patients because they want to know if they will be able to both achieve and maintain the high levels of clearance that we observe with biologic agents. This is important because there is the concern of developing antidrug antibodies with biologics over time, which may lead to secondary treatment failure. This mechanism of loss of treatment response is only applicable to biologics, thus offering some advantage to the use of small molecules for the treatment of psoriasis. Overall, some of the newer second-generation oral therapies are showing the ability to achieve biologic-like levels of skin improvement while also maintaining that durability, which gives patients the assurance that they are not going to have to switch to a new medication because of a loss of efficacy over time. However, measuring durability of treatment response in clinical trials can be challenging because you have to account for patient dropouts, and these dropouts may result in patient enrichment or selection bias, requiring caution when interpreting these results.

Two agents in the psoriasis treatment pipeline that were discussed at Maui Derm Hawaii 2025 are the TYK2 inhibitors ESK-001 and zasocitinib (TAK-279). The first-generation TYK2 inhibitor deucravacitinib set the bar for oral therapies, placing it well above apremilast in terms of both clinical efficacy and adverse events leading to treatment discontinuation. Now, the second generation of TYK2 inhibitors appears to have a better affinity for TYK2, or perhaps the molecule is just designed better, resulting in better inhibition of the pathways contributing to plaque psoriasis. Additionally, we are finding in clinical trials that patients’ clearance rates with second-generation TYK2 inhibitors are much faster than what we saw with deucravacitinib. These newer oral medications are convenient for patients, are well tolerated, and have adverse-event profiles that are similar to deucravacitinib, which does not have the boxed warning seen with other JAK inhibitors, such as those that inhibit JAK1/JAK2/JAK3. This represents a continuing improvement on what was already a big advancement in this space.

With both biologic and oral therapies, we are getting better at pushing our skin clearance percentages even higher, which makes psoriasis one of the most well-treated inflammatory conditions in all of medicine—because we are achieving unprecedented skin clearance rates. It is rewarding to be able to offer our patients with plaque psoriasis so many treatment options to choose from without the concerns that came along with first-generation biologics and other broad-acting immunosuppressants.