ABS0448 ZASOCITINIB (TAK-279), AN ORAL, ALLOSTERIC, SELECTIVE TYK2 INHIBITOR, IN MODERATE-TO-SEVERE PLAQUE PSORIASIS: EFFICACY ANALYSIS BY BASELINE CHARACTERISTICS FROM A RANDOMISED PHASE 2B TRIAL

Background: Zasocitinib (TAK-279) is a highly selective and potent, oral, allosteric tyrosine kinase 2 (TYK2) inhibitor. In a phase 2b trial of moderate-to-severe plaque psoriasis, the primary endpoint (psoriasis area and severity index [PASI] 75 response at Week 12) was met with zasocitinib 5, 15 and 30 mg once daily; 33% of patients receiving zasocitinib 30 mg achieved PASI 100 [1]. Objectives: To evaluate the influence of baseline characteristics on zasocitinib efficacy in patients with plaque psoriasis in the phase 2b trial. Methods: This was a phase 2b, randomised, multicentre, double-blind, placebo-controlled, multiple-dose study (NCT04999839). Post hoc analyses were performed on Week 12 PASI 75/90/100 responses, Physician Global Assessment (PGA) scores of clear (0) or almost clear (1), and Dermatology Life Quality Index (DLQI) scores stratified by weight, sex, age, race, disease duration, prior biologics use and baseline PASI. The treatment difference between zasocitinib groups and placebo was calculated using the Mantel–Haenszel method, and p values were calculated using a Cochran–Mantel–Haenszel test with prior biologic treatment included as a stratification factor; treatment difference estimates stratified by prior biologic treatment, in which treatment difference estimates were unadjusted and chi-square test was used to calculate p values. For DLQI, a mixed model for repeated measures was used to calculate the least square mean, with treatment, visit, treatment-by-visit interaction and prior biologic treatment (not included for the subgroup analysis by prior biologic treatment) as fixed effects and baseline score as the covariate. Results: Overall, 259 patients were included in this study. PASI 75 response rates with zasocitinib were greater than placebo regardless of weight (≤ 90 kg: placebo, 8.8%; 15 mg, 70.4%; 30 mg, 69.7%; > 90 kg: placebo, 0%; 15 mg, 65.4%; 30 mg, 63.2%, each p < 0.001), sex (male: placebo, 0%; 15 mg, 61.8%; 30 mg, 72.7%, each p < 0.001; female: placebo, 14.3%; 15 mg, 78.9% [ p < 0.001]; 30 mg, 57.9% [ p < 0.01]), age (≤ 40 years: placebo, 0%; 15 mg, 55.6% [ p < 0.01]; 30 mg, 62.5% [ p < 0.001]; > 40 years: placebo, 7.3%; 15 mg, 74.3%; 30 mg, 69.4%, each p < 0.001), race (White: placebo, 6.8%; 15 mg, 67.4%; 30 mg, 64.3%, each p < 0.001; non-White: placebo, 0%; 15 mg, 71.4% [ p < 0.05]; 30 mg, 80.0% [ p < 0.005], disease duration (≤ 10 years: placebo, 3.6%; 15 mg, 47.4%; 30 mg, 58.8%; >10 years: placebo, 8.3%; 15 mg, 79.4%; 30 mg, 71.4%, each p < 0.001), prior biologics (yes: placebo, 0%; 15 mg, 100% [ p < 0.001]; 30 mg, 37.5% [ p = 0.055, not significant]; no: placebo, 6.8%; 15 mg, 61.4%; 30 mg, 72.7%, each p < 0.001) and baseline PASI (≤ 16: placebo, 10.7%; 15 mg, 57.9%; 30 mg, 60.7%; > 16: placebo, 0%; 15 mg, 93.3%; 30 mg, 75.0%, each p < 0.001; Figure 1). PASI 90, PASI 100, PGA 0/1 and DLQI were also significantly improved with zasocitinib treatment versus placebo in almost all subgroups. Conclusion: Treatment with zasocitinib 15 mg or 30 mg demonstrated consistent improvements in PASI 75, PASI 90, PASI 100, PGA 0/1 and DLQI at Week 12 versus placebo in patients with moderate-to-severe plaque psoriasis, regardless of baseline weight, sex, age, disease duration, prior biologic use and PASI. Phase 3 trials (NCT06088043 and NCT06108544) are ongoing to investigate the efficacy and safety of zasocitinib in larger patient groups. REFERENCES: [1] Armstrong A, et al. JAMA Dermatol 2024;160:1066–74. Acknowledgements: This study was funded by Nimbus Discovery, Inc. and Takeda Development Center Americas, Inc. Writing assistance was provided by Tina Borg, PhD, of Oxford PharmaGenesis and funded by Takeda Development Center Americas, Inc. Nimbus refers to the group of entities including Nimbus Therapeutics LLC, Nimbus Discovery Inc., and Nimbus Lakshmi Inc. Disclosure of Interests: Nada Elbuluk has received royalties from McGraw Hill, has stock options in VisualDx, is a consultant, advisory board member, and/or speaker for AbbVie, Allergan, Avita, Beiersdorf, Dior, Eli Lilly, Galderma, Incyte, Janssen, La Roche Posay, L'Oreal, McGraw Hill, Medscape, Pfizer, Sanofi, Takeda, Unilever, VisualDx, and has received grant funding from Pfizer, Melinda Gooderham is an investigator, speaker and/or advisor for AbbVie, Akros, Amgen, AnaptysBio, Apogee, Arcutis Biotherapeutics, Aristea, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Dermira, Eli Lilly, Galderma, GSK, Incyte, Inmagene, JAMP, Janssen, Kyowa Kirin, LEO Pharma, MedImmune, Meiji, MoonLake Immunotherapeutics, Nimbus, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, Takeda, Tarsus Pharmaceuticals, UCB, Union Therapeutics, Ventyx Biosciences and Vyne Therapeutics, Jessamyn Blau is an equity holder and an employee of Takeda, Wenwen Zhang is an equity holder and an employee of Takeda, Jonathan Uy is an equity holder and an employee of Takeda, Warren Winkelman is an equity holder and an employee of Takeda, Mark Lebwohl is a consultant for Almirall, AltruBio, Apogee Therapeutics, Arcutis Biotherapeutics, AstraZeneca, Atomwise, Avotres, Boehringer Ingelheim, Bristol Myers Squibb, Castle Biosciences, Celltrion, CorEvitas, Dermavant, Dermsquared, Evommune, Facilitation of International Dermatology Education, Forte Biosciences, Galderma, Genentech, Incyte, LEO Pharma, Meiji Seika Pharma, Mindera, Pfizer, Sanofi-Regeneron, Seanergy, Strata, Takeda, Trevi Therapeutics and Verrica Pharmaceuticals, is an employee of Mount Sinai, and receives research funds from AbbVie, Arcutis Biotherapeutics, Avotres, Boehringer Ingelheim, Cara Therapeutics, Clexio Biosciences, Dermavant, Eli Lilly, Incyte, Inozyme, Janssen, Pfizer, Sanofi-Regeneron and UCB. © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.

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