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Clinical Trial
. 2025 Sep 27;406(10510):1363-1374.
doi: 10.1016/S0140-6736(25)01576-4. Epub 2025 Sep 18.

Once-daily oral icotrokinra versus placebo and once-daily oral deucravacitinib in participants with moderate-to-severe plaque psoriasis (ICONIC-ADVANCE 1 & 2): two phase 3, randomised, placebo-controlled and active-comparator-controlled trials

Linda Stein Gold  1 , April W Armstrong  2 , Robert Bissonnette  3 , Nina Magnolo  4 , Ronald B Vender  5 , Michael Sebastian  6 , Maria Laura Galimberti  7 , Athanasios Tsianakas  8 , Marcelo Arnone  9 , Paul Wallace  10 , Margrit Simon  11 , Josep Riera-Monroig  12 , Sascha Gerdes  13 , Jill Waibel  14 , Alvaro Gonzalez-Cantero  15 , Beate Schwarz  16 , Yayoi Tada  17 , Michael Cecchini  18 , Benjamin Ehst  19 , Leon Kircik  20 , Lea Kephart  21 , Ofelia Reyes-Servin  21 , Bassey Effiom Edem  22 , Jennifer H Campbell  23 , Yaung-Kaung Shen  21 , Kellen Cresswell  21 , Shu Li  21 , Cynthia M C DeKlotz  21 , Fabio Nunes  21 , Kim A Papp  24
Affiliations
Clinical Trial

Once-daily oral icotrokinra versus placebo and once-daily oral deucravacitinib in participants with moderate-to-severe plaque psoriasis (ICONIC-ADVANCE 1 & 2): two phase 3, randomised, placebo-controlled and active-comparator-controlled trials

Linda Stein Gold et al. Lancet. .

Abstract

Background: Monoclonal antibodies targeting interleukin-23 and interleukin-12 are efficacious in treating plaque psoriasis but must be delivered via intravenous or subcutaneous injection. Here, we aimed to evaluate the efficacy and safety of icotrokinra (JNJ-77242113), a targeted oral peptide that selectively binds the interleukin-23 receptor, compared with both placebo and deucravacitinib in adults with moderate-to-severe plaque psoriasis.

Methods: The phase 3, randomised, double-blind, placebo-controlled and active-comparator-controlled ICONIC-ADVANCE 1 and ICONIC-ADVANCE 2 trials, which are being done at 149 sites across 13 countries and 114 sites across 11 countries, respectively, randomly assigned (2:1:2 and 4:1:4, respectively) adults with moderate-to-severe plaque psoriasis diagnosed for at least 26 weeks (body-surface-area involvement ≤10%, Psoriasis Area and Severity Index [PASI] ≤12, and Investigator's Global Assessment [IGA] ≤3) to once-daily oral icotrokinra 200 mg, placebo, or deucravacitinib 6 mg; participants randomly assigned to placebo or deucravacitinib transitioned to icotrokinra at week 16 or week 24, respectively. Coprimary endpoints were proportions of participants achieving IGA 0 or 1 (clear or almost clear skin) with at least a two-grade improvement and at least 90% improvement in PASI (PASI 90) at week 16 with icotrokinra versus placebo. These studies are registered with ClinicalTrials.gov, NCT06143878 (ADVANCE 1) and NCT06220604 (ADVANCE 2), and are ongoing.

Findings: ICONIC-ADVANCE 1 enrolled participants from Jan 17, 2024, to May 24, 2024, and ICONIC-ADVANCE 2 enrolled participants from March 9, 2024, to June 13, 2024. Participants (ADVANCE 1: 774 of 988 patients screened; ADVANCE 2: 731 of 917 patients screened) were randomly assigned to icotrokinra (n=311 and 322), placebo (n=156 and 82), or deucravacitinib (n=307 and 327). All coprimary endpoints were met in both trials. Higher proportions of icotrokinra-treated versus placebo-treated participants achieved IGA 0 or 1 (ADVANCE 1: 213 [68%] of 311 vs 17 [11%] of 156, treatment difference 95% CI 58% [50-64]; ADVANCE 2: 227 [70%] of 322 vs seven [9%] of 82, 62% [53-69]; both p<0·0001) and PASI 90 (ADVANCE 1: 171 [55%] of 311 vs six [4%] of 156, treatment difference 95% CI 51% [44-57]; ADVANCE 2: 184 [57%] of 322 vs one [1%] of 82, 56% [48-62]; both p<0·0001) at week 16. Across studies, adverse event rates to week 16 were 303 (48%) of 632 and 136 (57%) of 237 with icotrokinra and placebo, respectively; the most common adverse events were nasopharyngitis (37 [6%] of 632 and 13 [5%] of 237) and upper respiratory tract infection (23 [4%] of 632 and eight [3%] of 237). To week 24, adverse event rates were lower than with icotrokinra (359 [57%] of 632) than deucravacitinib (411 [65%] of 634).

Interpretation: Icotrokinra showed superior clinical response rates versus placebo and deucravacitinib in phase 3 moderate-to-severe plaque psoriasis trials, with similar adverse event rates to placebo. These findings suggest the potential of once-daily oral icotrokinra to provide robust efficacy and a favourable safety profile.

Funding: Johnson & Johnson.

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Conflict of interest statement

Declaration of interests LSG is an investigator–advisor or speaker for AbbVie, Amgen, Arctis, Bristol Myers Squibb, Dermavant, Eli Lilly, Johnson & Johnson, Novartis, Pfizer, and UCB. AWA has served as a research investigator, scientific advisor, or speaker to AbbVie, Amgen, Arcutis, BMS, Boehringer Ingelheim, Dermavant Sciences, Eli Lilly, Galderma, Incyte, Johnson & Johnson, Leo Pharma, Novartis, Parexel, Pfizer, Regeneron, Sanofi, Takeda, and UCB. RB is an advisory board member, consultant, speaker, investigator for, or received honoraria or grants from AbbVie, Alumis, Amgen, AnaptysBio, Arcutis, BMS/Celgene, Eli Lilly, Johnson & Johnson, LEO Pharma, Organon, Nimbus, Takeda, UCB, VentyxBio, Vyne, Xencor, and Zurabio and is also an employee and shareholder of Innovaderm Research. NM has received honoraria for participation on advisory boards, as a speaker or for consultancy for AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Dr. Wolff, Eli Lilly, Johnson & Johnson, La Roche-Posay, LEO Pharma, Novartis, Pfizer, Sanofi, and UCB. RBV has received grants or research support, or speakers bureau–honoraria from AbbVie, Alumis, Amgen, Arcutis, Bausch, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Dermavant, Dermira, DICE, Galderma, Incyte, JAMP, Johnson & Johnson, Leo, Lilly, Meiji, Nimbus, Novartis, Organon, Orka, Pfizer, Sanofi, Sandoz, Sun, Takeda, UCB, and Zai. MS has received consulting fees or payment–honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, Almirall, Amgen, BMS, Leo Pharma, Sanofi, Galderma, UCB, Incyte, Johnson & Johnson, Lilly, Novartis, and Pfizer; has received payment for expert testimony from Apogee; and has received support for attending meetings or travel from AbbVie and Johnson & Johnson. MLG has served as an investigator for Amgen, BI, GSK, Johnson & Johnson, Lilly, Novartis, and Pfizer. AT has served as an investigator and received honoraria as advisor and speaker for Johnson & Johnson. MA has been a consultant or has received honoraria from AbbVie, Boehringer Ingelheim, Glenmark, Johnson & Johnson, Leo Pharma, Lilly, Novartis, Pfizer, and UCB Biopharma; has participated as an investigator in clinical studies; and has no other potential conflict of interest to declare. PW and MSi report no competing interests. JR-M has acted as consultant or speaker, or has received research funding from or participated in clinical trials for AbbVie, Almirall, Amgen, Boheringer Ingelheim, Bristol Myers Squibb, Johnson & Johnson, Leo Pharma, Lilly, Novartis, and UCB. SG served as an advisor, received speaker's honoraria or grants, or participated in clinical trials for AbbVie, Aceleryin, Adimune, Affibody, Akari Therapeutics, Almirall-Hermal, Alumis, Amgen, Apogee Therapeutics, Argenx, Aristea Therapeutics, AstraZeneca, Biogen Idec, Bioskin, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Dermira, Eli Lilly, Galderma, Hexal, Incyte, Johnson & Johnson, Klinge Pharma, Kymab, LEO Pharma, Medac, MoonLake Immunotherapeutics, MSD, Neubourg Skin Care GmbH, Novartis, Pfizer, Pierre Fabre, Principia Biopharma, Regeneron Pharmaceuticals, Sandoz Biopharmaceuticals, Sanofi-Aventis, and UCB Pharma. JW is an advisory board member, consultant, speaker or investigator and has received honoraria from Allergan, Amgen, Bellamia, BMS, Candela, Cytrellis, Eli Lilly, Galderma, Johnson & Johnson, Lumenis, Pfizer, Proctor and Gambel, ReGenX, Sanofi, SkinCeuticals, Shanghai Biopharma, Solta, and VA. AG-C has served as a consultant for AbbVie, Almirall, Amgen, Apogee, BMS, Boehringer Ingelheim, Celgene, Cerave, Innovaderm, Johnson & Johnson, Leo Pharma, Lilly, L’Oréal, Novartis, and Organon, receiving grants or other payments. BS has served as a speaker, consultant, or clinical study investigator for AbbVie, Almirall, BMS, Celgene, Biogen, Dermapharm, Ferrer, Galderma, Johnson & Johnson, Leo Pharma, Lilly Pharma, Moon Lake, Novartis, Regeneron, Sanofi, Pfizer, and UCB. YT received research grants from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eisai, Eli Lilly, Jimro, Kaken, Kyowa Kirin, LEO Pharma, Maruho, Meiji Seika Pharma, Sun Pharma, Taiho, Tanabe-Mitsubishi, Torii, and UCB and honoraria from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eisai, Eli Lilly, Jimro, Johnson & Johnson, Kyowa Kirin, LEO Pharma, Maruho, Novartis Pharma, Sun Pharma, Taiho, Tanabe-Mitsubishi, Torii, and UCB. MC reports no competing interests. BE has served as a consultant or clinical study investigator for AbbVie, Acelyrin, Aclaris, Allakos, Almirall, Alumis, Amgen, AnaptysBio, Apogee, Arcutis, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Celldex, Concert Pharma, Dermavant Sciences, Dermira, Eli Lilly, Evelo Biosciences, Evommune, Incyte, Johnson & Johnson, Kymab, LEO Pharma, Navigator Medicines, Novartis, Ortho Dermatologics, Pfizer, Priovant, Regeneron, Sanofi Genzyme, Sun Pharma, Takeda, UCB Pharma, and Ventyx, and as a paid speaker for AbbVie, Dermavant, Incyte, LEO Pharma, Eli Lilly, Novartis, Ortho Dermatologics, Regeneron, and Sanofi Genzyme. LKi has served as a speaker, consultant, advisory board member, or clinical study investigator for AbbVie, Abbott Laboratories, Allergan, Almirall, Amgen, Arcutis, Biogen-Idec, BMS, Celgene, Cipher, Combinatrix, Connetics Corporation, Dermavant, Dermira, Dr Reddy's Lab, Eli Lilly, Galderma, Genentech, GlaxoSmithKline, Johnson & Johnson, Leo, Merck, Novartis, Promius, PharmaDerm, Pfizer, Serono (Merck Serono International SA), Stiefel Laboratories, Sun Pharma, Taro, UCB, and Valeant Pharmaceuticals International. LKe, OR-S, BEE, JHC, Y-KS, KC, SL, CMCD, and FN are employees of Johnson & Johnson; employees can hold stock or stock options in Johnson & Johnson. KAP has received clinical research grants, honoraria, or consultancy, scientific advisor, investigator, speaker, or medical officer fees from AbbVie, Acelyrin, Akros, Alumis, Amgen, Arcutis, Bausch Health–Valeant, Boehringer Ingelheim, Bristol Myers Squibb, Can-Fite Biopharma, Celltrion, Concert Pharmaceuticals, Dermavant, Dermira, Dice Pharmaceuticals, Dice Therapeutics, Eli Lilly, Evelo Biosciences, Forbion, Galderma, Horizon Therapeutics, Incyte, Johnson & Johnson, Kymab, Kyowa Hakko Kirin, Leo, Meiji Seika Pharma, Mitsubishi Pharma, Nimbus Therapeutics, Novartis, Pfizer, Reistone, Sanofi-Aventis–Genzyme, Sandoz, Sun Pharma, Takeda, Tarsus Pharmaceuticals, UCB, and Zai Lab.

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