<p>The evolving understanding of plaque psoriasis continues to drive research into new-generation biologics and oral small-molecule inhibitors, with the goal of delivering more effective, convenient, and accessible treatment options for patients. Several presentations at the recent <strong>Maui Derm Hawaii 2026</strong> meeting discussed promising systemic therapies for moderate to severe plaque psoriasis.</p> <p><br></p> <p><em>Following these presentations, featured expert Eingun James Song, MD, FAAD, was interviewed by </em>Conference Reporter<em> Associate Editor-in-Chief Rick Davis, MS, RPh. Clinical perspectives from Dr Song on these findings are presented here.</em></p>

Several new biologic and oral small-molecule therapies for plaque psoriasis were discussed at Maui Derm Hawaii 2026. Two of these presentations were on ORKA-001, a novel IL-23 inhibitor with an extended half-life that binds to a similar epitope as risankizumab.

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In a phase 1 study, James G. Krueger, MD, PhD, and colleagues reported that ORKA-001 has an approximate half-life of 100 days, compared with 20 to 25 days for risankizumab. These data support the potential for once-yearly dosing with ORKA-001, rather than the every-12-week dosing schedule used for risankizumab. Further, EVERLAST-A, a 52-week phase 2a study by Andrew Blauvelt, MD, MBA, et al, also presented at the meeting, is currently underway and is evaluating ORKA-001 in adults with moderate to severe plaque psoriasis using a 600-mg induction dose—4 times the dose of risankizumab for psoriasis—with an off-treatment arm for patients who achieve Psoriasis Area and Severity Index (PASI) 100 at week 28.

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Three oral therapies are currently in phase 3 trials for moderate to severe plaque psoriasis: icotrokinra, zasocitinib, and envudeucitinib. Icotrokinra is the furthest along of the 3 and is a once-daily oral peptide that blocks the IL-23R rather than the cytokine itself. Importantly, icotrokinra appears to perform on par with many newer biologics, marking the first time an oral therapy has demonstrated efficacy within the range of our best biologic agents. This was further supported by a network meta-analysis presented by April W. Armstrong, MD, MPH, at Maui Derm Hawaii 2026 showing that icotrokinra was comparable to IL-23–inhibiting biologics in achieving complete skin clearance.

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Data for next-generation TYK2 inhibitors zasocitinib and envudeucitinib were also presented. These agents are similar to deucravacitinib in that they are highly selective allosteric inhibitors of TYK2, thereby minimizing unwanted off-target effects on other JAK proteins. However, these next-generation TYK2 inhibitors are even more selective and have higher binding affinity, leading to more complete and prolonged inhibition of IL-23 signaling.

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While phase 2 data for zasocitinib have been presented at previous meetings, at Maui Derm Hawaii 2026, Kenneth B. Gordon, MD, shared the most recent top-line results from 2 pivotal phase 3 studies. These data—released just days before the meeting—show that more than half of patients achieved PASI 90 and approximately 30% achieved PASI 100 by week 16 with once-daily zasocitinib 30 mg, with response rates continuing to increase through week 24.

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Data for envudeucitinib 40 mg twice daily from the 52-week phase 2 STRIDE study by Dr Blauvelt and colleagues were also presented, demonstrating strong and durable efficacy, with PASI 75 achieved in 77.5% of patients, PASI 90 in 61.3%, and PASI 100 in 38.8% at week 52. In addition, recent top-line results from pivotal phase 3 studies were discussed, showing that 74% of patients achieved PASI 75 and 59% achieved static Physician’s Global Assessment (sPGA) scores of 0/1 by week 16. By week 24, 65% of patients achieved PASI 90 and more than 40% achieved PASI 100.

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Overall, the safety profiles of all 3 oral agents are reassuring, with a small but consistent signal for acne observed with the TYK2 inhibitors. In terms of dosing, icotrokinra and zasocitinib are administered once daily, whereas envudeucitinib is given twice daily, although a once-daily extended-release formulation is also in development. Taken together, these data suggest that we may soon have 3 oral therapies that could serve as legitimate first-line options for moderate to severe plaque psoriasis with efficacies that rival some of our best biologic agents.