J&J Medical Connect
icotrokinra
+ Save link
J&J Medical Connect

Connect with us

Connect with us

This information is intended for US healthcare professionals to access current scientific information about J&J Innovative Medicine products. It is prepared by Medical Information and is not intended for promotional purposes, nor to provide medical advice.

icotrokinra

Medical Information

Icotrokinra – Overview of the ICONIC-ADVANCE Program

Last Updated: 09/25/2025

SUMMARY

  • Icotrokinra (JNJ-77242113) is a targeted oral peptide that selectively binds the interleukin-23 (IL-23) receptor and inhibits IL-23 pathway signaling.1 
  • Icotrokinra is being studied in five plaque psoriasis (PsO) phase 3 clinical trials (ICONIC-LEAD, ICONIC-TOTAL, ICONIC-ADVANCE 1, ICONIC-ADVANCE 2, ICONIC-ASCEND).2-6  
  • ICONIC-ADVANCE 1 and ICONIC-ADVANCE 2 are ongoing, phase 3, multicenter, randomized, double-blind, placebo (PBO)– and active-comparator (deucravacitinib)–controlled studies (NCT06143878 and NCT06220604) evaluating the efficacy and safety of icotrokinra 200 mg by mouth (PO) daily in adults with moderate-to-severe plaque PsO.1 
    • At week 16, a significantly higher proportion of patients in the icotrokinra group achieved the co-primary endpoint of Investigator’s Global Assessment score of 0 or 1 (IGA 0/1), with a ≥2-grade improvement from baseline, compared to those in the PBO group (ADVANCE 1: 68% vs 11%, P<0.0001; ADVANCE 2: 70% vs 9%, P<0.0001).
    • Similarly, for the co-primary endpoint of ≥90% improvement from baseline in Psoriasis Area and Severity Index (PASI 90), significantly more patients receiving icotrokinra achieved PASI 90 response at week 16 vs those receiving PBO (ADVANCE 1: 55% vs 4%, P<0.0001; ADVANCE 2: 57% vs 1%, P<0.0001).
    • At week 16, a higher proportion of patients in the icotrokinra group achieved IGA 0/1 response vs those receiving deucravacitinib (ADVANCE 1: 68% vs 50%, P<0.0001; ADVANCE 2: 70% vs 54%, P<0.0001). Findings were consistent at week 24.
    • In addition, more patients in the icotrokinra cohort experienced clear skin (IGA 0) and PASI 100 response at week 16 compared to those in the deucravacitinib cohort (ADVANCE 1, IGA 0: 37% vs 16%; ADVANCE 2, IGA 0: 37% vs 17%; ADVANCE 1, PASI 100: 31% vs 11%; ADVANCE 2, PASI 100: 32% vs 14%; all P values were <0.0001). Similar results were obtained at week 24. All other key secondary endpoints are summarized below.
    • Through week 16, across both studies, 48%, 57%, and 57% of patients receiving icotrokinra, PBO, and deucravacitinib, respectively, reported at least 1 adverse event (AE). The most common AEs were nasopharyngitis and upper respiratory tract infection. Through week 24, across both studies, serious AEs occurred in 3% of the icotrokinra group and 3% of the deucravacitinib group.

CLINICAL DATA

ICONIC-ADVANCE 1 and ICONIC-ADVANCE 2

Stein Gold et al (2025)1 reported results through week 24 from ICONIC-ADVANCE 1 and ICONIC-ADVANCE 2, two phase 3, multicenter, randomized, double-blind clinical trials evaluating the efficacy and safety of icotrokinra compared to PBO and deucravacitinib for the treatment of adults with moderate-to-severe plaque PsO.

Study Design/Methods


Select Inclusion/Exclusion Criteria for ICONIC-ADVANCE 1 and ICONIC-ADVANCE 21 
Inclusion Criteria
Exclusion Criteria
  • Adults (≥18 years of age) with moderate-to-severe plaque PsO diagnosed for ≥26 weeks at screening
  • Total BSA involvement of ≥10%, PASI score of ≥12, and IGA score of ≥3 at screening
  • Candidate for phototherapy or systemic treatment
  • Nonplaque form of PsO (eg, erythrodermic, guttate, or pustular)
  • Drug-induced PsO
  • Chronic or recurrent infectious disease, immunodeficiency, or serious infection within 8 weeks of screening
  • History of untreated latent TB or positive interferon gamma release assay within 8 weeks of first study dosea
  • Primary efficacy failure or clinically significant side effects related to IL-23 or TYK2 inhibitors (except for prior IL-12/23 biologic failure)
Abbreviations: BSA, body surface area; IGA, Investigator’s Global Assessment; IL, interleukin; PASI, Psoriasis Area and Severity Index; PsO, psoriasis; TB, tuberculosis; TYK2, tyrosine kinase 2.aPatients with treated latent TB were eligible, as long as treatment was initiated before first dose of study drug and not prematurely discontinued during the trial.1 
  • Patients were randomized to once-daily icotrokinra 200 mg PO, PBO, or deucravacitinib 6 mg PO, with PBO crossover to icotrokinra at week 16 and deucravacitinib crossover to icotrokinra at week 24. ADVANCE 1 and ADVANCE 2 utilized different randomization ratios (2:1:2 and 4:1:4, respectively). See Figure: ICONIC-ADVANCE Program Study Design.1 

ICONIC-ADVANCE Program Study Design1,7

A close-up of a graph AI-generated content may be incorrect.

Abbreviations: ADV, ADVANCE; Deucra, deucravacitinib; ICO, icotrokinra; IGA, Investigator’s Global Assessment; PASI, Psoriasis Area and Severity Index; PBO, placebo; R, randomized; QD, daily; W, week.


Key Outcomes in the ICONIC-ADVANCE Program1 
Coprimary Endpoints
Time Frame
Icotrokinra versus PBO
Percentage of patients who achieved an IGA score of 0 (clear skin) or 1 (almost clear skin) with a ≥2-grade improvement from baseline
Week 16
Percentage of patients who achieved PASI 90 response
Week 16
Key Secondary Endpoints
Icotrokinra versus PBO
Percentage of patients who achieved IGA score of cleared (0)
Week 16
Percentage of patients who achieved PASI 75 response
Weeks 4 and 16
Percentage of patients who achieved PASI 90 response
Week 8
Percentage of patients who achieved PASI 100 response
Week 16
Percentage of patients who achieved ss-IGA score of 0 (absence of disease) or 1 (very mild disease) with a ≥2-grade improvement from baseline
Week 16
Percentage of patients who achieved PSSD symptom score of 0
Weeks 8 and 16
Percentage of patients with ≥4-point improvement from baseline in PSSD Itch score (CMI)
Weeks 4 and 16
Icotrokinra versus deucravacitinib
Percentage of patients who achieved an IGA score of 0 (clear skin) or 1 (almost clear skin) with a ≥2-grade improvement from baseline
Weeks 16 and 24
Percentage of patients who achieved IGA score of 0 (clear skin)
Weeks 16 and 24
Percentage of patients who achieved PASI 75, PASI 90, and PASI 100 responses
Weeks 16 and 24
Percentage of patients who achieved PSSD symptom score of 0
Week 16
Abbreviations: CMI, clinically meaningful improvement; IGA, Investigator’s Global Assessment; PASI, Psoriasis Area and Severity Index; PBO, placebo; PSSD, Psoriasis Symptoms and Signs Diary; ss-IGA, scalp-specific Investigator’s Global Assessment.Note: Additional details regarding study outcomes can be found on clinicaltrials.gov.
  • In both studies, the efficacy analysis included all randomized patients, with a composite strategy (non-responder imputation) being utilized for the coprimary endpoints. The safety analysis set in both studies included all randomized and treated patients. Of note, safety data from ICONIC-ADVANCE 1 and ICONIC-ADVANCE 2 were combined to identify any uncommon AEs.1 

Results

Patient Characteristics


Select Baseline Demographics and Clinical Characteristics1 
ICONIC-ADVANCE 1
ICONIC-ADVANCE 2
ICO
(n=311)
PBO
(n=156)
Deucra (n=307)
ICO (n=322)
PBO (n=82)
Deucra (n=327)
Demographics
Age, years, mean (SD)
47.1 (13.19)
46.9 (12.78)
46.3 (13.87)
45.9 (13.78)
48.4 (13.90)
45.6 (13.22)
Male sex, n (%)
223 (72)
105 (67)
200 (65)
218 (68)
55 (67)
223 (68)
White race, %
231 (74)
118 (76)
221 (72)
274 (85)
65 (79)
265 (81)
Weight, kg, mean (SD)
86.9 (21.08)
88.2 (25.08)
87.7 (23.04)
88.8 (20.12)
86.4 (18.84)
89.8 (21.43)
Disease Characteristics
Duration of PsO, years, mean (SD)
17.52 (11.10)
17.88 (12.75)
16.81 (12.81)
17.43 (13.38)
21.21 (15.17)
16.82 (12.03)
PASI total score (0-72), median (IQR)
18.60 (15.50,
22.70)
17.15 (14.40,
21.65)
18.00 (15.00,
23.40)
18.00
(15.10,
22.20)
17.95
(14.30,
23.60)
17.60 (15.20,
21.40)
% BSA with PsO,
median (IQR)a
20.00 (16.00,
32.00)
20.00 (14.00,
30.75)
21.00 (14.00,
34.00)
21.00
(15.00,
32.00)
22.00
(15.00,
33.00)
20.00 (15.50,
32.00)
IGA score of 3 (moderate),
n (%)
251 (81)
123 (79)
242 (79)
252 (78)
67 (82)
267 (82)
IGA score of 4 (severe),
n (%)
60 (19)
33 (21)
65 (21)
70 (22)
15 (18)
60 (18)
ss-IGA scoreb
    2 (mild), n (%)
45 (15)
30 (19)
55 (18)
62 (19)
17 (21)
62 (19)
    3 (moderate), n (%)
177 (58)
85 (55)
166 (54)
169 (53)
48 (59)
176 (54)
    4 (severe), n (%)
39 (13)
19 (12)
47 (15)
39 (12)
6 (7)
40 (12)
Previous PsO Therapy
Systemic therapy, n (%)c
236 (76)
110 (71)
225 (73)
225 (70)
58 (71)
230 (70)
    Phototherapyd
112 (36)
53 (34)
97 (32)
98 (30)
31 (38)
109 (33)
    Biologic therapye
86 (28)
42 (27)
80 (26)
78 (24)
26 (32)
77 (24)
Abbreviations: BSA, body surface area; deucra, deucravacitinib; IGA, Investigator’s Global Assessment; PASI, Psoriasis Area Severity Index; PsO, psoriasis; PUVA, psoralen and ultraviolet A radiation; QD, daily; SD, standard deviation; ss-IGA, scalp-specific Investigator’s Global Assessment; UVB, ultraviolet B.
aAmong 322, 82, and 327 participants in the ICO, PBO, and Deucra groups, respectively, in ADVANCE 2.
bAmong 308, 156, and 306 participants in the ICO, PBO, and Deucra groups, respectively, in ADVANCE 1 and 321, 82, and 324 participants, respectively, in ADVANCE 2.
cIncludes conventional nonbiologic systemics, novel nonbiologic systemics, 1,25-vitamin D3 and analogues, phototherapy, and biologics.
dIncludes PUVA and UVB.eIncludes etanercept, infliximab, adalimumab, ustekinumab, briakinumab, secukinumab, ixekizumab, brodalumab, guselkumab, risankizumab, tildrakizumab, alefacept, efalizumab, natalizumab, and cetolizumab pegol.

Efficacy


Co-primary and Key Secondary Endpoints (Icotrokinra vs PBO)1,8 
ICONIC-ADVANCE 1
ICONIC-ADVANCE 2
% (n)
Icotrokinra
(N=311)
PBO
(N=156)
Difference (95% CI)
Adjusted
P-value
Icotrokinra (N=322)
PBO
(N=82)
Difference (95% CI)
Adjusted
P-value
Primary Endpoints
IGA 0/1 at Week 16
68% (213)
11% (17)
58% (50, 64)
<0.0001
70% (227)
9% (7)
62% (53, 69)
<0.0001
PASI 90 at Week 16
55% (171)
4% (6/156)
51% (44, 57)
<0.0001
57% (184)
1% (1)
56% (48, 62)
<0.0001
Key Secondary Endpoints
PASI 75 at Week 16
74% (231)
12% (18)
63% (55, 69)
<0.001
77% (249)
10% (8)
68% (58, 74)
<0.001
PASI 100 at Week 16
31% (97)
1% (2)
30% (24, 36)
<0.001
32% (102)
1% (1)
30% (24, 36)
<0.001
IGA 0 at Week 16a
37% (114)
2% (3)
35% (29,41)
<0.001
37% (118)
1% (1)
36% (28, 42)
<0.001
PSSD Symptom 0 at Week 16b
24% (68)
3% (4)
21% (15, 27)
<0.001
21% (64)
0
22% (15, 27)
<0.001
CMI in PSSD Itch score at Week 16c
62% (155)
17% (19)
45% (35, 54)
<0.001
60% (155)
15% (9)
46% (34, 56)
<0001
ss-IGA 0/1 at Week 16d
72% (189)
21% (28)
51% (42, 59)
<0.001
74% (199)
18% (13)
56% (44, 65)
<0.001
PASI 90 at Week 8
20% (62)
1% (2)
19% (14, 24)
<0.001
25% (81)
0
25% (20, 30)
0.004
PSSD Symptom 0 at Week 8b
8% (24)
2% (3)
6% (1, 11)
0.011
9% (27)
1% (1)
8% (-1, 12)
0.025
PASI 75 at Week 4
12% (38)
3% (4)
10% (5, 14)
<0.001
16% (52)
4% (3)
12% (5, 18)
0.004
CMI in PSSD Itch score at Week 4c
22% (56)
7% (8)
15% (8, 22)
<0.001
21% (54)
5% (3)
16% (6, 22)
0.008
Abbreviations: CI, confidence interval; CMI, clinically meaningful improvement in itch (≥4 points); Deucra, deucravacitinib; IGA, Investigator’s Global Assessment; PASI, Psoriasis Area Severity Index; PBO, placebo; PSSD, Psoriasis Symptoms and Signs Diary; ss-IGA, scalp-specific Investigator’s Global Assessment.
aAmong the 311, 156, and 307 patients with an IGA score ≥2 at baseline in the ICO, PBO, and Deucra groups, respectively, in ADVANCE 1 and 322, 82, and 327 in ADVANCE 2.bAmong the 286, 142, and 272 patients with a baseline PSSD Symptom score >0 in the ICO, PBO, and Deucra groups, respectively, in ADVANCE 1, and 298, 71, and 287 participants, respectively, in ADVANCE 2.cAmong the 251 and 115 patients with a baseline PSSD itch score ≥4 in the ICO and PBO groups, respectively, in ADVANCE 1 and 258 and 61 participants, respectively, in ADVANCE 2.dAmong the 261 and 134 patients with a baseline ss-IGA score ≥2 in the ICO and PBO groups, respectively, in ADVANCE 1, and the 270 and 71 participants, respectively, in ADVANCE 2.Note: Endpoints are listed in accordance with the order in which they were tested for statistical significance.

Key Secondary Endpoints (Icotrokinra vs Deucravacitinib)1,8 
ICONIC-ADVANCE 1
ICONIC-ADVANCE 2
% (n)
Icotrokinra
(N=311)
Deucra
(N=156)
Difference (95% CI)
Adjusted
P-value
Icotrokinra (N=322)
Deucra
(N=82)
Difference (95% CI)
Adjusted
P-value
IGA 0/1 at Week 16a
68% (213)
50% (154)
18% (11, 26)
<0.001
70% (227)
54% (177)
16% (9, 24)
<0.001
PASI 75 at Week 16
74% (231)
57% (176)
17% (10, 24)
<0.001
77% (249)
61% (198)
17% (10, 24)
<0.001
IGA 0 at Week 16a
37% (114)
16% (48)
21% (14, 28)
<0.001
37% (118)
17% (57)
19% (13, 26)
<0.001
PASI 90 at Week 16
55% (171)
30% (91)
25% (18, 33)
<0.001
57% (184)
34% (111)
23% (16, 30)
<0.001
PASI 100 at Week 16
31% (97)
11% (34)
20% (14, 26)
<0.001
32% (102)
14% (46)
18% (11, 24)
<0.001
PSSD Symptom 0 at Week 16b
24% (68)
9% (25)
14% (8, 21)
<0.001
21% (64)
13% (36)
9% (3, 15)
0.004
IGA 0 at Week 24a
48% (150)
21% (63)
28% (20, 35)
<0.001
40% (128)
21% (68)
19% (12, 26)
<0.001
PASI 90 at Week 24
66% (205)
41% (127)
24% (17, 32)
<0.001
65% (208)
43% (141)
22% (14, 29)
<0.001
PASI 100 at Week 24
41% (129)
16% (49)
26% (19, 32)
<0.001
33% (107)
16% (52)
17% (11, 24)
<0.001
IGA 0/1 at Week 24a
74% (230)
52% (161)
22% (14, 29)
<0.001
68% (220)
55% (179)
14% (6, 21)
<0.001
PASI 75 at Week 24
82% (254)
64% (196)
18% (11, 25)
<0.001
83% (266)
66% (216)
17% (10, 23)
<0.001
Abbreviations: CI, confidence interval; CMI, clinically meaningful improvement in itch (≥4 points); Deucra, deucravacitinib; IGA, Investigator’s Global Assessment; PASI, Psoriasis Area Severity Index; PBO, placebo; PSSD, Psoriasis Symptoms and Signs Diary.
aAmong the 311, 156, and 307 patients with an IGA score ≥2 at baseline in the ICO, PBO, and Deucra groups, respectively, in ADVANCE 1 and 322, 82, and 327 in ADVANCE 2.bAmong the 286, 142, and 272 patients with a baseline PSSD Symptom score >0 in the ICO, PBO, and Deucra groups, respectively, in ADVANCE 1, and 298, 71, and 287 participants, respectively, in ADVANCE 2.Note: Endpoints are listed in accordance with the order in which they were tested for statistical significance.

Safety

  • A total of 632, 237, and 634 patients in the icotrokinra, PBO, and deucravacitinib groups were included in the combined safety analysis set.1 
  • Through week 16, 48% (303/632), 57% (136/237), and 57% (360/634) of patients receiving icotrokinra, PBO, and deucravacitinib, respectively, reported ≥1 AE(s).1 
    • The most common AEs were nasopharyngitis and upper respiratory tract infection.
    • Gastrointestinal AEs occurred in 7% (45/632), 6% (15/237), and 10% (63/634) of patients in the icotrokinra, PBO, and deucravacitinib groups, respectively.
  • Through week 24, AE rates were lower in the icotrokinra group versus the deucravacitinib group (57% vs 65%), and no safety signals were identified.1 
  • See Table: Combined AEs from the ICONIC-ADVANCE 1 and ICONIC-ADVANCE 2 Safety Analysis Sets.1  

Combined AEs from the ICONIC-ADVANCE 1 and ICONIC-ADVANCE 2 Safety Analysis Setsa,1 
PBO-controlled
(W0-16)
Active-comparator controlled (W0-24)
Crossover
(W16-24)
ICO
PBO
Deucra
ICO
Deucra
PBO→ICO
Number of participants
632
237
634
632
634
215
Mean weeks of follow up (SD)
15.9 (1.88)
15.5 (2.69)
15.8 (2.25)
23.5 (3.26)
23.3 (3.94)
8.1 (0.58)
≥1 AE
303 (48)
136 (57)
360 (57)
359 (57)
411 (65)
60 (28)
AEs occurring in ≥5% of patients in any treatment group, n (%)
    Headache
26 (4)
11 (5)
19 (3)
28 (4)
20 (3)
3 (1)
    Nasopharyngitis
37 (6)
13 (5)
58 (9)
56 (9)
77 (12)
8 (4)
    Upper Respiratory tract infection
23 (4)
8 (3)
33 (5)
32 (5)
49 (8)
7 (3)
Serious AE, n (%)
14 (2)
4 (2)
14 (2)
18 (3)
20 (3)
3 (1)
    Serious infectionb
1 (<1)
1 (<1)
4 (1)
3 (<1)
4 (1)
0 (0)
AE resulting in discontinuation, n (%)
13 (2)
12 (5)
14 (2)
15 (2)
17 (3)
0 (0)
GI AEs, n (%)
45 (7)
15 (6)
63 (10)
55 (9)
80 (13)
5 (2)
Malignancy, n (%)c
3 (<1)
1 (<1)
1 (<1)
3 (<1)
2 (<1)
0 (0)
Active TB, n (%)
0 (0)
0 (0)
0(0)
0 (0)
0 (0)
0 (0)
Abbreviations: AE, adverse events; Deucra, deucravacitinib; GI, gastrointestinal; ICO, icotrokinra; PBO, placebo; SD, standard deviation; TB, tuberculosis.
aThe safety analysis set included all randomized and treated participants.bSerious infections included bacterial arthritis (PBO group), campylobacter colitis (Deucra group), viral infection (Deucra group), infection exacerbated by chronic obstructive airways disease (ICO group), lower respiratory tract infection (Deucra group), viral upper respiratory tract infection (Deucra group), and pneumonia (ICO group).cDetails on malignancies reported through Week 24 of both studies are provided as early as Week 4.8 
  • Through week 16, there were five instances of malignancy reported across ADVANCE 1 and ADVANCE 2: three in the icotrokinra group (pancreatic carcinoma, breast cancer, and keratoacanthoma), one in the PBO group (invasive ductal breast carcinoma), and one in the deucravacitinib group (right buccal SCC). All events were considered unrelated to study treatments by investigators.1 

Literature Search

A literature search of MEDLINE®, EMBASE®, BIOSIS Previews®, and DERWENT® (and/or other resources, including internal/external databases) was conducted on 3 September 2025.

 

References

Show
1 Stein Gold L, Armstrong AW, Bissonnette R, et al. 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. The Lancet. 2025.  
2 Janssen Research & Development, LLC. A study of JNJ-772421113 for the treatment of participants with plaque psoriasis involving special areas (scalp, genital, and/or palms of the hands and the soles of the feet) (ICONIC-TOTAL). ln: ClinicalTrial.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2025 Sep 15].  Available from: https://clinicaltrials.gov/study/NCT06095102 NLM identifier: NCT06095102.  
3 Janssen Research & Development, LLC. A study of JNJ-77242113 for the treatment of participants with moderate to severe plaque psoriasis. ln: ClinicalTrial.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2025 Sep 18]. Available from: https://clinicaltrials.gov/study/NCT06143878 NLM Identifier: NCT06143878.  
4 Janssen Research & Development, LLC. A study of JNJ-77242113 in adolescent and adult participants with moderate to severe plaque psoriasis (ICONIC-LEAD). ln: ClinicalTrial.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2025 Sep 15]. Available from: https://clinicaltrials.gov/study/NCT06095115 NLM Identifier: NCT06095115.  
5 Janssen Research & Development, LLC. A study of JNJ-77242113 for the treatment of participants with moderate to severe plaque psoriasis (ICONIC-ADVANCE 2). ln: ClinicalTrial.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2025 Sep 12]. Available from: https://clinicaltrials.gov/study/NCT06220604 NLM Identifier: NCT06220604.  
6 Janssen Research & Development, LLC. A study to assess efficacy and safety of JNJ-77242113 compared to placebo and ustekinumab in participants with moderate to severe plaque psoriasis (ICONIC-ASCEND). ln: ClinicalTrial.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2025 Sep 12]. Available from: https://clinicaltrials.gov/study/NCT06934226 NLM identifier: NCT06934226.  
7 Stein Gold L, Armstrong AW, Bissonnette R, et al. Icotrokinra demonstrated superior responses compared with placebo and deucravacitinib in the treatment of moderate-to-severe plaque psoriasis. Oral presentation presented at: European Academy of Dermatology and Venereology (EADV); September 17-20, 2025; Paris, France.  
8 Stein Gold L, Armstrong AW, Bissonnette R, et al. Supplement to: 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. The Lancet. 2025.