<p>Developments in the understanding of plaque psoriasis have highlighted the need for new therapeutic agents, particularly as some patients may not respond to existing biologics or may experience a loss of efficacy over time. This has prompted ongoing research on new-generation agents that could provide more effective and accessible treatment options.</p>

One potentially exciting therapy in the pipeline for patients with plaque psoriasis is the IL-23R blocker icotrokinra. It is a unique small-molecule oral peptide that is taken once daily. Phase 3 study data show that it has potent efficacy and gets a large percentage of patients to Psoriasis Area and Severity Index (PASI) 90 and even PASI 100. In the phase 3 ICONIC-LEAD study, nearly 2 of 3 patients with plaque psoriasis who were taking icotrokinra reached PASI 90 in 24 weeks, and that percentage might be larger with more time on treatment. These results do not match the efficacy seen in the phase 3 trials of our best biologics, but they do approach the potency of the phase 3 results of some of the second-tier biologics. Icotrokinra’s mechanism of action is IL-23 pathway inhibition, which we already know is well tolerated. If approved by the US Food and Drug Administration (FDA), it will likely have a similar label to those of other IL-23 inhibitors. Icotrokinra appears to be the most promising pipeline drug in the next year and could represent a sea change in how we use oral therapy.

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Behind that, there are 2 TYK2 inhibitors in development for plaque psoriasis: zasocitinib and ESK-001. Both are purported to be improvements on deucravacitinib, with improved efficacy potentially derived from their highly selective action and improved affinity for their target: the regulatory domain of the TYK2 kinase. Phase 3 trials are still ongoing. In phase 2 trials, we saw PASI 75 achievement in the 60% to 70% range, but we do not yet know what the PASI 90 response will be. It is almost certain that these follow-on TYK2 inhibitors will have similar labels to that of deucravacitinib, so there will likely be monitoring requirements. We also know that acne is a side effect of this class in a minority of patients, and I would expect that to be the case with these emerging agents as well.

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The next category of interesting agents in development for plaque psoriasis is the long half-life biologic therapies that may allow for less frequent dosing. Currently, our least frequently dosed biologics, which include IL-23 inhibitors, are given every 8 to 12 weeks after initial dosing. ORKA-001 is an IL-23 inhibitor entering phase 2 trials that has been engineered to potentially stay in circulation longer. Essentially, it is a half-life extender. We could see similar or improved efficacy with less frequent dosing over the long haul—ideally once every 6 months or maybe, in some instances, once per year. Obviously, this would be appealing to our patients. Similarly, long half-life IL-17 inhibitors are also in development.

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The paradigm is shifting away from what we were previously accustomed to. I can imagine high levels of comfort with these newer therapeutics, with exciting advancements in both the oral and biologic spaces.