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icotrokinra

Medical Information

Icotrokinra – Overview of the ICONIC-LEAD Clinical Trial

Last Updated: 11/20/2025

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-LEAD is an ongoing, phase 3, multicenter, randomized, double-blind, placebo (PBO)-controlled study (NCT06095115) evaluating the efficacy and safety of icotrokinra 200 mg by mouth (PO) daily in patients ≥12 years of age with moderate to severe plaque PsO.4
  • Results for the co-primary endpoints at week 16 were as follows:1,7 
    • Investigator’s Global Assessment (IGA) score of 0 or 1 with a ≥2-grade improvement from baseline was achieved by 65% of patients receiving icotrokinra compared to 8% of patients receiving PBO (P<0.001).
    • Psoriasis Area and Severity Index (PASI) 90 was achieved by 50% of patients receiving icotrokinra compared to 4% of patients receiving PBO (P<0.001).
  • Clear skin at week 16 was achieved at higher rates in the icotrokinra group versus the PBO group (IGA 0: 33% vs 1%; PASI 100: 27% vs <1%; both P<0.001).
    • Results for other key secondary endpoints are summarized below.
  • In a subgroup analysis of patients with high-impact site involvement, patients receiving icotrokinra showed improvements at week 16 and week 24 in scalp, genitalia, hands/feet, and fingernail assessments.8 
  • In a subgroup analysis of adolescents receiving icotrokinra, IGA 0/1 at week 16 and week 24 was achieved by 84.1% and 86.4% of patients, respectively, and PASI 90 at week 16 and week 24 was achieved by 70.5% and 88.6% of patients, respectively.9 
  • At week 52, 82% of adolescents in the icotrokinra group and 91% of adolescents who crossed over from placebo to icotrokinra at week 16 achieved IGA 0/1 response with a ≥2-grade improvement from baseline. Similarly, 86% of adolescents in the icotrokinra group and 77% of adolescents who crossed over from placebo to icotrokinra at week 16 achieved PASI 90 response.10 
  • Among adult patients who were considered icotrokinra responders at week 24, the proportion of patients on icotrokinra who maintained PASI 75, PASI 90, and IGA 0/1 responses at week 52 was 89%, 84%, and 82%, respectively.10 
  • Through week 16, 49% of patients receiving icotrokinra and 49% of patients receiving PBO reported ≥1 adverse event (AE). The most common AEs were nasopharyngitis and upper respiratory tract infection.1
  • The icotrokinra AE profile through week 52 was consistent with that observed through week 16.10

CLINICAL DATA

ICONIC-LEAD

Bissonnette et al (2025)1,7 reported results through week 24 from ICONIC-LEAD, a phase 3, multicenter, randomized, double-blind, PBO-controlled clinical trial evaluating the efficacy and safety of icotrokinra compared to PBO for the treatment of adults and adolescents (≥12 years of age) with moderate to severe plaque PsO.

González Cantero et al (2025)11 evaluated icotrokinra effect on relative PASI improvements and achievement of absolute PASI (aPASI) thresholds through week 24 in patients from ICONIC-LEAD.

Study Design/Methods


Key Inclusion and Exclusion Criteria for ICONIC-LEAD1,4,7,9 
Inclusion Criteria
Exclusion Criteria
  • Age ≥12 years with moderate to severe plaque PsO diagnosed for ≥26 weeks at screening who were candidates for phototherapy or systemic therapy
  • At screening and baseline:
    • Total BSA involvement of ≥10%
    • PASI ≥12
    • IGA ≥3
  • Body weight ≥40 kg (adolescents)
  • Nonplaque form of PsO (eg, erythrodermic, guttate, or pustular) or drug-induced PsO
  • Severe, progressive or uncontrolled renal, liver, cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disease
  • Prior primary efficacy failure or AE related to ≥1 biologic targeting IL-23 (prior IL-12/23 biologic failure was allowed)
Abbreviations: AE, adverse event; BSA, body surface area; IGA, Investigator’s Global Assessment; IL, interleukin; kg, kilograms; PASI, Psoriasis Area and Severity Index; PsO, psoriasis.
  • Adult and adolescent patients were randomized in a 2:1 ratio to receive icotrokinra 200 mg PO daily or PBO daily, with PBO crossover to icotrokinra at week 16 (see Figure: ICONIC-LEAD Study Design).7

ICONIC-LEAD Study Design7

A diagram of a computer AI-generated content may be incorrect.

Abbreviations: IGA, Investigator’s Global Assessment; PASI, Psoriasis Area and Severity Index; PBO, placebo; R, randomized; QD, daily; WK, week.


ICONIC-LEAD Key Clinical Trial Outcome Measures1,4,7,10
Coprimary Endpoints
Time Frame
Percentage of patients who achieved an IGA score of cleared (0) or minimal (1) with a ≥2-grade improvement from baseline
Week 16
Percentage of patients who achieved PASI 90 response
Week 16
Key Secondary Endpoints
Percentage of patients who achieved IGA score of cleared (0)
Week 16
Percentage of patients who achieved PASI 75 response
Weeks 4, 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 absence of disease (0) or very mild disease (1) and had 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
Weeks 4 and 16
Percentage of adult patients who achieved PASI 75/PASI 90 response (among responders at week 24)
Week 52
Time to loss of PASI 75/PASI 90 response (among adult responders at week 24)
Week 52
Other Prespecified Endpoints
Percentage of adult patients who achieved IGA 0/1 with a ≥2-grade improvement from baseline (among responders at week 24)
Week 52
Time to loss of IGA 0/1 response (among adult responders at week 24)
Week 52
Percent improvement in PASI score
Week 16
Percentage of patients who achieved aPASI thresholds of ≤5, ≤4, ≤3, ≤2, ≤1, and 0
Week 24
Abbreviations: aPASI, absolute PASI; IGA, Investigator’s Global Assessment; PASI, Psoriasis Area and Severity Index; PSSD, Psoriasis Symptoms and Signs Diary; ss-IGA, scalp-specific Investigator’s Global Assessment.Note: Additional details regarding study outcome definitions can be found on clinicaltrials.gov.

Results

Patient Characteristics


Demographics and Baseline Clinical Characteristics1,7,8
Icotrokinra
N=456
Placebo
N=228
Demographics
  Age, years, mean (SD)
42.4 (16.3)
43.2 (16.6)
    Adolescent cohort, years, mean (SD)
15 (1.8)
15 (1.5)
  Male, %
64
68
  Race, Asian/Black/White, %
24 / 1 / 72
25 / <1 / 72
  BMI, kg/m2, mean (SD)a
29.2 (6.9)
29.3 (7)
Disease Characteristics
  PsO disease duration, years, mean (SD)
17.3 (13.9)
16.6 (12.7)
  % BSA with PsO, mean (SD)
24.6 (14.3)
27.1 (16.2)
  IGA score of 3, moderate, %
75
76
  IGA score of 4, severe, %
25
24
  PASI (0-72), mean (SD)
19.4 (7.1)
20.8 (8.1)
PsO involving the scalp
  ss-IGA score of 3, moderateb, %
59
51
  ss-IGA score of 4, severeb, %
17
22
Previous Therapy, %
  Systemic therapyc
72
71
    Biologic therapyd
32
37
    Phototherapy (PUVA and UVB)
30
29
High Impact Sites
  ss-IGA score ≥3, %
75
72
  sPGA-G score ≥3, %
20
19
  hf-PGA score ≥3, %
23
21
  f-PGA score ≥2, %
30
29
  mNAPSI score >0, %
43
44
    mNAPSI score, mean
17.7
19.1
Abbreviations: BMI, body mass index; BSA, body surface area; f-PGA, fingernail Physician’s Global Assessment; hf-PGA, hand/foot Physician’s Global Assessment; IGA, Investigator’s Global Assessment; mNAPSI, modified Nail Psoriasis Severity Index; PASI, Psoriasis Area Severity Index; PsO, psoriasis; PUVA, psoralen plus ultraviolet A; QD, daily; SD, standard deviation; sPGA-G, Static Physician’s Global Assessment of Genitalia; ss-IGA, scalp-specific Investigator’s Global Assessment; UVB, ultraviolet B.
aIcotrokinra: n=455; Placebo: n=227.
bIcotrokinra: n=451; Placebo: n=227.
cIncludes conventional nonbiologic systemics, novel nonbiologic systemics, 1,25-vitamin D3 and analogues, phototherapy, biologics.
dIncludes adalimumab, alefacept, briakinumab, brodalumab, certolizumab pegol, efalizumab, etanercept, guselkumab, infliximab, ixekizumab, natalizumab, risankizumab, secukinumab, tildrakizumab, and ustekinumab

Efficacy


Coprimary, Key Secondary, and Other Prespecified Endpoints1,7,11,12 
n (%)
ICO
200 mg QD
N=456
PBO
N=228
Treatment difference
(95% CI)
PBO→ICO Crossovera
N=213
Proportion of patients achieving
  IGA 0/1 with a ≥2-grade improvement from baseline
    Week 16 – coprimary endpoint
295 (65)
19 (8)
56.4% (50.4-61.7)
P<0.001b
-
    Week 24
338 (74)
-
-
135 (63)
  PASI 90
    Week 8
98 (21)
3 (1)
20.1% (15.9–24.5)
P <0.001b
-
    Week 16 – coprimary endpoint
226 (50)
10 (4)
45.1% (39.5-50.4)
P<0.001b
-
    Week 24
296 (65)
-
-
87 (41)
  PASI 75
    Week 4
68 (15)
5 (2)
12.7% (8.8-16.6) P=0.002b
-
    Week 16
315 (69)
25 (11)
58.1% (51.9–63.6)
P<0.001b
-
    Week 24
368 (81)
-
-
149 (70)
  IGA 0
    Week 16
152 (33)
3(1)
31.9% (27.2–36.6)
P<0.001b
-
    Week 24
211 (46)
-
-
49 (23)
  PASI 100
    Week 16
123 (27)
1 (<1)
26.5% (22.4–30.8)
P<0.001b
-
    Week 24
184 (40)
-
-
29 (14)
PSSD symptom score of 0c
    Week 8
29/408 (7)
3/208 (1)
5.7% (2.0–8.9)
P=0.002b
-
    Week 16
82/408 (20)
2/208 (1)
19.2% (15.0–23.6)
P<0.001b
-
    Week 24
153/408 (38)
-
-
43/194 (22)
≥4 point improvement in PSSD itch score from baselined
    Week 4
67/350 (19)
9/176 (5)
14.1% (8.6–19.3)
P=0.002b
-
    Week 16
203/350 (58)
23/176 (13)
45.2% (37.5–52.0)
P<0.001b
-
    Week 24
255/350 (73)
-
-
116/166 (70)
ss-IGA 0/1 and ≥2-grade improvement from baselinee
    Week 16
293/405 (72)
30/200 (15)
57.0% (49.9–63.1)
P<0.001b
-
    Week 24
326/405 (80)
-
-
143/186 (77)
Mean percent PASI improvement, %
  Week 16
79% (N=439)
23% (N=222)
Nominal P<0.001f
-
  Week 24
88% (N=438)
-
-
80% (N=212)
Median percent PASI improvement, %
  Week 16
91% (N=439)
17% (N=222)
-
-
  Week 24
97% (N=438)
-
-
86% (N=212)
Proportion of patients achieving, %
N=456
N=228
N=214
aPASI ≤2g
Week 16
53%
5%
Nominal P<0.001h
-
Week 24
67%
-
-
44%
aPASI ≤1
Week 16
39%
3%
Nominal P<0.001h
-
Week 24
55%
-
-
32%
aPASI 0
Week 16
27%
<1%
Nominal P<0.001h
-
Week 24
40%
-
-
14%
Abbreviations: aPASI; absolute Psoriasis Area Severity Index; CI, confidence interval; ICO, icotrokinra; IGA, Investigator’s Global Assessment; MMRM, Mixed-Effects Model for Repeated Measures; PASI, Psoriasis Area Severity Index; PBO, placebo; PSSD, Psoriasis Symptom and Sign Diary; QD, daily; ss-IGA, scalp-specific Investigator’s Global Assessment.
aPatients crossed over from placebo to icotrokinra at week 16.
bP-values were calculated based on Cochran-Mantel-Haenszel chi-square test stratified by age group, baseline weight category (adults only), and geographic region (if applicable). Fisher’s exact test was used for PSSD symptom 0 at week 8. P-values for key secondary endpoints were adjusted for multiplicity.
cAmong participants with a baseline PSSD Symptom score >0.dAmong patients with a baseline PSSD Itch score ≥4.
eAmong patients with baseline ss-IGA score ≥2.fP-values based on the MMRM model with treatment group, visit, treatment group by visit interaction, age group, baseline weight, geographic region, baseline PASI total score, and baseline PASI total score by visit interaction as covariates. The endpoint was not controlled for multiple comparisons. Therefore, the P-value is nominal, and statistical significance has not been established.gPer the British Association of Dermatologists Biologics and Immunomodulators Register, a relevant treat-to-target approach for a clinical setting is aPASI ≤2.hP-values based on Cochran-Mantel-Haenszel chi-square test stratified by age group, baseline weight category for adults, and geographic region. The endpoint was not controlled for multiple comparisons. Therefore, the P-value is nominal, and statistical significance has not been established.

ICONIC-LEAD: High-Impact Site Involvement

Soung et al (2025)8 conducted subgroup analyses to evaluate the effect of icotrokinra in adult and adolescent patients with plaque PsO and high-impact site involvement (scalp, genitals, hands/feet, nails) through week 24.

Results


High-impact Site Response Rates in Adult and Adolescent Patients8,12
% (n/N)
Icotrokinra
Placebo
Treatment difference
(95% CI)
Proportion of patients achieving
  ss-IGA 0/1a
    Week 16
72.4 (249/344)
13.9 (23/165)
58.4% (50.8-64.8)b
Nominal P<0.001c
    Week 24
80.8 (278/344)
-
-
  ss-IGA 0a
    Week 16
52.9 (182/344)
9.1 (15/165)
43.6% (36.5-50.1)b
Nominal P<0.001c
    Week 24
65.1 (224/344)
-
-
  sPGA-G 0/1d
    Week 16
70.7 (65/92)
38.6 (17/44)
33.8% (15.7-49.6)b
Nominal P<0.001c
    Week 24
80.4 (74/92)
-
-
  sPGA-G 0d
    Week 16
57.6 (53/92)
25.0 (11/44)
34.4% (16.6-49.3)b
Nominal P<0.001c
    Week 24
69.6 (64/92)
-
-
  hf-PGA 0/1e
    Week 16
74.0 (77/104)
23.4 (11/47)
50.6% (34.2-63.6)b
Nominal P<0.001c
    Week 24
76 (79/104)
-
-
  hf-PGA 0e
    Week 16
58.7 (61/104)
17.0 (8/47)
42.0% (25.9-54.8)b
Nominal P<0.001c
    Week 24
62.5 (65/104)
-
-
  f-PGA 0/1f
    Week 16
50.4 (69/137)
21.2 (14/66)
30.1% (16.4-42.0)b Nominal P<0.001c
    Week 24
63.5 (87/137)
-
-
  f-PGA 0f
    Week 16
24.1 (33/137)
12.1 (8/66)
11.9% (0.2-22.0)b Nominal P<0.05c
    Week 24
29.2 (40/137)
-
-
mNAPSI, LS mean % improvement from baseline (95% CI)g,h
  Week 16
-43.5 (22.99-63.99); n=187
-2.2 (23.29-27.76);
n=98
41.3% (12.8-69.7)
Nominal P<0.01h
Abbreviations: CI, confidence interval; CMH, Cochran-Mantel-Haenszel; f-PGA, fingernail Physician’s Global Assessment; hf-PGA, hand/foot Physician’s Global Assessment; LS, least squares; MMRM, Mixed-Effects Model for Repeated Measures; mNAPSI, modified Nail Psoriasis Severity Index; sPGA-G, Static Physician’s Global Assessment of Genitalia; ss-IGA, scalp-specific Investigator’s Global Assessment; QD, daily.
aAmong patients with a baseline ss-IGA score ≥3.
bTreatment difference and 95% CI (using Miettinen-Nurminen method) were calculated adjusting for age group, baseline weight category for adults, and geographic region (for ss-IGA endpoints) using Mantel-Haenszel weights. cP-values were based on CMH test stratified by age group, baseline weight category for adults, and geographic region (for ss-IGA endpoints). The endpoint was not controlled for multiple comparisons. Therefore, the P-value is nominal, and statistical significance has not been established.
dAmong patients with a baseline sPGA-G score ≥3.
eAmong patients with a baseline hf-PGA score ≥3.
fAmong patients with a baseline f-PGA score ≥2.gAmong patients with a baseline mNAPSI score >0.hLS mean, LS mean difference, and P-value were based on the MMRM model with treatment group, visit, treatment group by visit interaction, age group, baseline weight, geographic region, baseline mNAPSI total score, and baseline mNAPSI total score by visit interaction as covariates. The endpoint was not controlled for multiple comparisons. Therefore, the P-value is nominal, and statistical significance has not been established.

ICONIC-LEAD: Adolescent SUBGROUP

Eichenfield et al and Bissonnette et al (2025)1,9 reported top line results through week 24 from a subgroup analysis of adolescent patients with moderate-to-severe plaque PsO.

Soung et al (2025)10 reported longer-term icotrokinra effects in adolescent patients through week 52.

Results

Patient Characteristics


Demographics and Baseline Clinical Characteristics in Adolescents1 
Icotrokinra
(n=44)
Placebo
(n=22)
Demographics
  Age, years, mean (SD)
15.0 (1.8)
15.0 (1.5)
  Male, %
48
36
  Race, Asian/Black/White, %
23/5/70
23/0/77
  BMI, kg/m2, mean (SD)
26.0 (7.1)
24.4 (7.9)
Disease Characteristics
  PsO disease duration, years, mean (SD)
4.9 (4.0)
5.8 (3.4)
  % BSA with PsO, mean (SD)
26.1 (15.6)
27.1 (14.0)
  IGA score of 3, moderate, %
70
82
  IGA score of 4, severe, %
30
18
  PASI (0-72), mean (SD)
19.8 (8.2)
18.6 (4.0)
Previous Therapy, %
  Phototherapy (PUVA and UVB)
23
14
  Systemic therapya
52
50
    Biologic therapyb
14
41
Abbreviations: BMI, body mass index; BSA, body surface area; IGA, Investigator’s Global Assessment; PASI, Psoriasis Area Severity Index; PsO, psoriasis; PUVA, psoralen plus ultraviolet A; SD, standard deviation; UVB, ultraviolet B.
aIncludes conventional nonbiologic, novel nonbiologic, 1,25-vitamin D3 and analogues, phototherapy, and biologics.
bIncludes adalimumab, alefacept, briakinumab, brodalumab, certolizumab pegol, efalizumab, etanercept, guselkumab, infliximab, ixekizumab, natalizumab, risankizumab, secukinumab, tildrakizumab, and ustekinumab

Efficacy


Key Prespecified Endpoints in Adolescents1,9,10,12,13 
n (%)
Icotrokinra
N=44
Placebo
N=22
Placebo→Icotrokinra
Crossovera
N=22
  IGA 0/1 and ≥2-grade improvement from baseline
    Week 16
37 (84)b,c
6 (27)
-
    Week 24
38 (86.4)
-
18 (81.8)
    Week 52
36 (81.8)
-
20 (90.9)
  PASI 90
    Week 8
14 (32)
1 (5)
-
    Week 16
31 (70)b,d
3 (14)
-
    Week 24
39 (88.6)
-
11 (50)
    Week 52
38 (86.4)
-
17 (77.3)
  IGA 0
    Week 16
18 (40.9)b,e
1 (4.5)
-
    Week 24
33 (75)
-
9 (40.9)
  PASI 75
Week 4
10 (23)
2 (9)
-
Week 16
38 (86)b,f
5 (23)
-
    Week 24
40 (90.9)
-
17 (77.3)
    Week 52
42 (95.5)
-
20 (90.9)
  PASI 100
    Week 16
13 (30)b,g
1 (5)
-
    Week 24
28 (63.6)
-
5 (22.7)
Abbreviations: CI, confidence interval; IGA, Investigator’s Global Assessment; PASI, Psoriasis Area Severity Index.aPBO→ICO group includes patients receiving PBO who crossed over to receive ICO at week 16 through week 24.
bNominal P-values versus placebo (P<0.001 for IGA 0/1 and PASI 90; P<0.01 for IGA 0; and P<0.05 for PASI 100). These endpoints were not controlled for multiple comparisons. Therefore, the P-values are nominal, and statistical significance has not been established.cIGA 0/1 at week 16: treatment difference of 56.2% (95% CI, 33.2-74.1).dPASI 90 at week 16: treatment difference of 56.3% (95% CI, 32.5-73.0).eIGA 0 at week 16: treatment difference of 35.7% (95% CI, 14.6-51.9).fPASI 75 at week 16: treatment difference of 63.3% (95% CI, 39.7-79.7).gPASI 100 at week 16: treatment difference of 24.4% (95% CI, 4.9-40.6).Note: 95% CIs are based on the normal assumption without adjustment (Wald Method). P-values derived from Cochran-Mantel-Haenszel chi-square test stratified by geographic region.

ICONIC-LEAD: Week 24-52 Randomized Withdrawal

Soung et al (2025)10 reported maintenance of icotrokinra clinical response during the randomized-withdrawal period, which included adult week-24 icotrokinra responders who were re-randomized in a 1:1 ratio to either continue icotrokinra or receive placebo through week 52. For more details, see Figure: ICONIC-LEAD Study Design.

Results

Patient Characteristics


Baseline Characteristics – Adult Week-24 Icotrokinra Respondersa,10 
Icotrokinra → Icotrokinra
N=169
Icotrokinra → Placebo
N=172
Demographics
  Age, years, mean (SD)
46.5 (14.4)
44.5 (14.4)
  Female, %
30
38
  Race, Asian/Black/White, %
23 / 1 / 74
24 / 1 / 73
  BMI, kg/m2, mean (SD)
29.0 (6.8)
29.7 (6.7)
Disease Characteristics
  PsO disease duration, years, mean (SD)
19.2 (14.1)
18.6 (13.9)
  % BSA with PsO, mean (SD)
24.8 (14.0)
24.9 (14.7)
  IGA score of 3, moderate, %
74
78
  IGA score of 4, severe, %
26
22
  PASI (0-72), mean (SD)
19.6 (6.7)
19.2 (7.3)
Previous Therapy, %
  Phototherapy (PUVA or UVB)
31
31
  Systemic therapyb
76
72
    Biologic therapyc
35
33
Abbreviations: BMI, body mass index; BSA, body surface area; IGA, Investigator’s Global Assessment; PASI, Psoriasis Area Severity Index; PsO, psoriasis; PUVA, psoralen plus ultraviolet A; SD, standard deviation; UVB, ultraviolet B.
aAdults randomized to icotrokinra at baseline who were PASI 75 or IGA 0/1 responders at Week 24.bIncludes conventional nonbiologic systemics, novel nonbiologic systemics, 1,25-vitamin D3 and analogues, phototherapy, and biologics.
cIncludes adalimumab, alefacept, briakinumab, brodalumab, certolizumab pegol, efalizumab, etanercept, guselkumab, infliximab, ixekizumab, natalizumab, risankizumab, secukinumab, tildrakizumab, and ustekinumab.

Efficacy


Maintenance of Response in Adult Week-24 Icotrokinra Responders through Week 5210 
Icotrokinra → Icotrokinra
Icotrokinra → Placebo
PASI 75
n=161
n=166
  Week 52
89%a
30%
  Median time to LOR, weeks
Not reached
16.9
PASI 90
n=128
n=129
  Week 52
84%a
21%
  Median time to LOR, weeks
Not reached
10.1
IGA 0/1
n=150
n=150
  Week 52
82%b
23%
  Median time to LOR, weeks
Not reached
10.1
Abbreviations: IGA, Investigator’s Global Assessment; PASI, Psoriasis Area Severity Index; LOR, loss of response.
aMultiplicity-adjusted P<0.001 versus placebo.
bNominal P<0.001 versus placebo. The endpoint was not controlled for multiple comparisons. Therefore, the P-value is nominal, and statistical significance has not been established.Note: P-values for response rates (Cochran-Mantel-Haenszel chi-square test) and time to LOR (log-rank test) were stratified by geographic region and, for PASI 75 and IGA 0/1, by PASI 90 response status at week 24.

ICONIC-LEAD: Safety

Adverse Events in the Overall Population

  • Through week 16, 49% of patients in each group (icotrokinra and PBO) reported ≥1 AE, with nasopharyngitis and upper respiratory tract being the most common.1 
    • Through week 16, 23% (107/456) and 22% (51/228) of patients in the icotrokinra and PBO groups, respectively, reported an infection.
  • The icotrokinra AE profile through week 52 was consistent with that observed through week 16 (see Table: Adverse Events in the Overall Study Population through Week 52).1,7,10 

Adverse Events in the Overall Study Population through Week 521,7,10 
PBO-Controlled
(Adults & Adolescents)
Active Treatment
(Adults & Adolescents)
ICO Responders Re-Randomized at W24 (Adults)
ICO
(W0-16)
N=456
PBO
(W0-16)
N=228
ICOa
(W16-52) N=213
ICO
(W0-52) N=456
ICO→ICO (W24-52) N=168
ICO→PBOb (W24-52) N=172
Mean weeks of follow-up
15.9
15.8
35.3
43.4
27.7
27.8
Any AE
226 (50%)
112 (49%)
132 (62%)
313 (69%)
92 (55%)
82 (48%)
  Most common AEs (≥5%)
    Nasopharyngitis
31 (7%)
15 (7%)
23 (11%)
64 (14%)
21 (12%)
20 (12%)
    Upper respiratory  tract infection
30 (7%)
16 (7%)
24 (11%)
52 (11%)
9 (5%)
15 (9%)
SAEc
6 (1%)
6 (3%)
4 (2%)
16 (4%)
3 (2%)
5 (3%)
Serious Infection
1 (<1%)
0
1 (<1%)
1 (<1%)
0
1 (1%)
AE leading to discontinuationd
6 (1%)
1 (<1%)
4 (2%)
10 (2%)
1 (1%)
3 (2%)
Gastrointestinal AE
26 (6%)
13 (6%)
9 (4%)
51 (11%)
7 (4%)
8 (5%)
Active tuberculosis
0
0
0
0
0
0
Malignancye
2 (<1%)
0
0
2 (<1%)
0
0
Abbreviations: AE, adverse events; ICO, icotrokinra; PBO, placebo; SAEs, serious adverse events; W, week.
aIncludes data after week 16 for PBO-randomized patients who crossed over to receive ICO.bCombined withdrawal and retreatment group.cSAEs through week 16 included acute cholecystitis, concussion, craniofacial fracture, pelvic fracture, psoriasis, and hypertensive urgency in the placebo group; and adenocarcinoma of the colon, prostate cancer, pancreatitis, bacterial gastroenteritis, arthralgia, and subarachnoid hemorrhage in the icotrokinra group.
dAEs leading to discontinuation through week 16 included blood glucose increase in the placebo group; and adenocarcinoma of the colon, prostate cancer, hypertriglyceridemia, subarachnoid hemorrhage, erectile dysfunction, and psoriasis in the icotrokinra group.
eIncluded adenocarcinoma of the colon (1 patient who had a history of smoking; the patient reported mild gastroenteritis during screening, severe colitis starting on study day 7, and severe ileus on day 14 leading up to the diagnosis of grade 3 adenocarcinoma of the colon on day 19) and prostate cancer (1 patient who had a history of smoking and a family history of prostate cancer; grade 1 prostate cancer was diagnosed on study day 48).

Adverse Events in the Adolescent Subgroup

  • AE findings in the adolescent subgroup were consistent with those in the overall patient population (see Table: Adverse Events in Adolescents through Week 16).1,9 
    • Through week 16, the rates of clinical laboratory abnormalities were similar between the icotrokinra and PBO groups and remained low through week 24.9 
    • Through week 24, no safety signals were identified, and no deaths, active tuberculosis, or malignancies were reported in the icotrokinra group.9 

Adverse Events in Adolescents through Week 169
Icotrokinra 200 mg QD
(n=44)
Placebo
(n=22)
Mean weeks of follow-up
16.2
16.2
Any AE
22 (50%)
16 (73%)
Infection
14 (32%)
6 (27%)
   Upper respiratory tract infection
6 (14%)
1 (4%)
   Nasopharyngitis
5 (11%)
3 (14%)
SAE
2 (4%)a,b
0
Abbreviations: AE, adverse events; CT, computed tomography; QD, daily; SAE, serious adverse event.
aSeventeen year-old female with a medical history of obesity and a gastric sleeve procedure leading to rapid weight loss before entering the study. CT and ultrasound showed pancreatitis due to choledocholithiasis. Cholecystectomy was performed and she was discharged in good condition. Treatment was interrupted but resumed after resolution and she continues in the study.
bSeventeen year-old female with a medical history of joint pain was admitted to the hospital at week 4 of the study for further diagnostic evaluation of joint pain. No imaging studies were completed. Treatment was continued without interruption. She was discharged the next day in good condition. No diagnosis was confirmed.

Literature Search

A literature search of MEDLINE®, EMBASE®, BIOSIS Previews®, and DERWENT® (and/or other resources, including internal/external databases) was conducted on 7 November 2025.

 

References

Show
1 Bissonnette R, Soung J, Hebert AA, et al. Oral icotrokinra for plaque psoriasis in adults and adolescents. N Engl J Med. 2025;393:1784-1795.  
2 Janssen Research & Development, LLC. A study of JNJ-77242113 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: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2025 October 10]. 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: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2025 October 10]. 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: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2025 October 10]. 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: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2025 October 10]. 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: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2025 October 10]. Available from: https://clinicaltrials.gov/study/NCT06934226 NLM Identifier: NCT06934226.  
7 Bissonnette R, Soung J, Adelaide H, et al. Icotrokinra, a targeted oral peptide that selectively blocks the interleukin-23-receptor, for the treatment of moderate-to-severe plaque psoriasis: results through week 24 of the phase 3, randomized, double-blind, placebo-controlled ICONIC-LEAD trial. Oral Presentation presented at: American Academy of Dermatology; March 7-11, 2025; Orlando, FL.  
8 Soung J, Chih-ho Hong H, Ehst B, et al. Treatment of plaque psoriasis involving high-impact sites with icotrokinra: subgroup analyses of the phase 3, ICONIC-LEAD trial. Poster presented at: AAD Innovation Academy; July 10-13, 2025; Chicago, IL.  
9 Eichenfield L, Galimberti R, Hebert A, et al. Icotrokinra, a novel targeted oral peptide (IL-23R-inhibitor), in adolescents with moderate-to-severe plaque psoriasis: results of subgroup analyses from a phase 3, randomized, double-blind, placebo-controlled study (ICONIC-LEAD). Oral Presentation presented at: World Congress of Pediatric Dermatology; April 8-11, 2025; Buenos Aires, Argentina.  
10 Soung J, Cui Y, Bissonnette R, et al. Maintenance of response with icotrokinra, a targeted oral peptide, for the treatment of moderate-to-severe plaque psoriasis: randomized treatment withdrawal in adults (weeks 24-52) and continuous treatment in adolescents (through week 52) from the phase 3, ICONIC-LEAD trial. Oral Presentation presented at: European Academy of Dermatology and Venereology (EADV); September 17-20, 2025; Paris, France.  
11 González-Cantero Á, Soung J, Ehst B, et al. High-level improvements in psoriasis area and severity index with icotrokinra in participants with moderate-to-severe plaque psoriasis: results through week 24 of the phase 3 ICONIC-LEAD study. Poster presented at: European Academy of Dermatology and Venereology (EADV); September 17-20, 2025; Paris, France.  
12 Data on File. Icotrokinra. Clinical Study Report 77242113PSO3001. Janssen Research & Development, LLC. EDMS-RIM-1306643; 2025.  
13 Bissonnette R, Soung J, Hebert AA, et al. Supplement to: Oral icotrokinra for plaque psoriasis in adults and adolescents. N Engl J Med. 2025;393:1784-1795.