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icotrokinra

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Icotrokinra - Treatment of Genital Psoriasis

Last Updated: 03/12/2026

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
  • The safety and efficacy of icotrokinra in patients with moderate to severe plaque psoriasis (PsO) was evaluated in the ICONIC-TOTAL (NCT06095102), ICONIC-LEAD (NCT06095115), ICONIC-ADVANCE 1 (NCT06143878), and ICONIC-ADVANCE 2 (NCT06220604) phase 3 clinical trials. Summarized below are data specific to genital PsO in the ICONIC-TOTAL and ICONIC-LEAD studies.1-7
    • In ICONIC-TOTAL, at week 16, 77% vs 21% of patients in the icotrokinra vs placebo (PBO) group achieved a static Physician’s Global Assessment of Genitalia (sPGA-G) score of 0 or 1 (sPGA-G 0/1, clear or minimal; treatment difference, 55.4%; 95% confidence interval [CI], 39.1-68.0; P<0.001).1,3 
      • At week 16, 62% vs 10% of patients in the icotrokinra vs PBO groups achieved an sPGA-G 0 response.
    • In a subgroup analysis of ICONIC-LEAD, at week 16, 71% vs 39% of patients in the icotrokinra vs PBO groups achieved an sPGA-G 0/1 response (treatment difference, 33.8%; 95% CI, 15.7-49.6; nominal P<0.001).2,4 
      • At week 16, 58% vs 25% of patients in the icotrokinra vs PBO groups achieved an sPGA-G 0 response (adjusted treatment difference, 34.4%; 95% CI, 16.6-49.3; nominal P<0.001).

CLINICAL DATA

ICONIC-TOTAL

Gooderham et al (2025)1 and Lain et al (2025)3 evaluated the efficacy and safety of oral icotrokinra 200 mg once daily in patients ≥12 years of age with plaque PsO affecting high-impact sites (scalp, genitals, and/or hands/feet) in an ongoing phase 3, multicenter, randomized, double-blind, PBO-controlled study.

Study Design/Methods

  • Key inclusion criteria1:
    • Age ≥12 years with plaque PsO diagnosed for ≥26 weeks at screening; candidate for phototherapy or systemic therapy with an inadequate response to ≥1 topical therapies
    • Total body surface area (BSA) involvement ≥1% and an Investigator’s Global Assessment (IGA) score ≥2
    • Involvement of ≥1 high-impact sites with at least moderate severity (scalp-specific IGA score ≥3, sPGA-G score ≥3, Physician’s Global Assessment (PGA) of hands and feet score ≥3)
  • Patients were randomized (2:1) to receive oral icotrokinra 200 mg or PBO once daily, with PBO crossover to icotrokinra at week 16.1 
  • The primary and select key secondary outcome measures are described in Table: Select ICONIC-TOTAL Outcome Measures at Week 16.

Select ICONIC-TOTAL Outcome Measures at Week 161
Primary Endpoint
Percentage of patients who achieved an IGA score of clear (0) or minimal (1) and ≥2-grade improvement from baseline
Select Key Secondary Endpoints
Percentage of patients who achieved an sPGA-G score of clear (0) or minimal (1)
Percentage of patients who achieved GPSS Genital Itch NRS ≥4-point improvement from baseline
Percentage of patients who achieved GenPs-SFQ Item 2 score of 0/1
Abbreviations: GenPs-SFQ, Genital Psoriasis Sexual Frequency Questionnaire; GPSS, Genital Psoriasis Symptoms Scale; IGA, Investigator’s Global Assessment; NRS, Numeric Rating Scale; sPGA-G, static Physician’s Global Assessment of Genitalia.

Results

Patient Characteristics
  • A total of 311 patients (icotrokinra, n=208; PBO, n=103) were included in the study, with 64.3% being male and 78.1% being White. The mean age was 44.7 years (6 patients were ≥12 to <18 years old).6
  • In the icotrokinra and PBO groups, respectively, 47.1% (98/208) and 40.8% (42/103) of patients had at least moderate genital PsO at baseline (sPGA-G score≥3).6
    •  Moderate genital PsO: 76.5% (icotrokinra, 75/98) vs 69% (PBO, 29/42)
    • Severe genital PsO: 22.4% (icotrokinra, 22/98) vs 28.6% (PBO 12/42)
    • Very severe genital PsO: 1.0% (icotrokinra, 1/98 vs 2.4% (PBO, 1/42)
Efficacy
  • Primary endpoint: At week 16, 56.7% (118/208) vs 5.8% (6/103) of patients receiving icotrokinra vs PBO, respectively, achieved an IGA 0/1 response (adjusted treatment difference, 51.1%; 95% CI, 42.1-58.8; P<0.001).1 
  • Select endpoints are described in Table: Select ICONIC-TOTAL Endpoints.1,3

Select ICONIC-TOTAL Endpoints1,3
ICO
(n=98)
PBO
(n=42)
Treatment Difference
(95% CI);
Adjusted P-valuea
PBO→ICO Crossoverb
(n=36)
Proportion of patients achieving endpoint, %
   sPGA-G 0/1c
      Week 16
77
21
55.4 (39.1-68.0);
P<0.001
-
      Week 52
85
-
-
94
   sPGA-G 0c
      Week 16
62
10
Nominal P<0.001d
-
      Week 52
73
-
-
86
   GPSS Genital Itch NRS score ≥4-point improvemente
      Week 16, n/N (%)
44/69 (64)
4/31 (13)
49.8 (31.3-64.3); P=0.008
   GenPs-SFQ Item 2 score of 0/1f
      Week 16, n/N (%)
44/55 (80)
9/25 (36)
43.2 (20.2-62.4); P=0.008
Abbreviations: CI, confidence interval; CMH, Cochran–Mantel–Haenszel; GenPs-SFQ, Genital Psoriasis Sexual Frequency Questionnaire; GPSS, Genital Psoriasis Symptoms Scale; ICO, icotrokinra; NRS, Numeric Rating Scale; PBO, placebo; sPGA-G, static Physician’s Global Assessment of Genitalia.
aP-values for key secondary endpoints were adjusted for multiplicity. P-values were based on CMH chi-square test stratified by BSA category.
bPatients crossed over from PBO to ICO at week 16.
cAmong patients with a baseline sPGA-G score ≥3.
dNominal P-value <0.001 for ICO vs PBO. The endpoint was not controlled for multiple comparisons. Therefore, the P-value is nominal, and statistical significance has not been established.eOnly patients with baseline scores of GPSS Genital Itch NRS ≥4 and sPGA-G ≥3 were included.
fOnly patients with baseline scores of GenPs-SFQ Item 2 ≥2 and sPGA-G ≥3 were included.
Safety
  • Through week 16, 50% (105/208) of patients receiving icotrokinra and 45% (46/103) of patients receiving PBO reported ≥1 adverse events (AE).3 
  • Through week 52, 74% (153/208) of patients receiving icotrokinra and 68% (204/300) of patients in the icotrokinra combined group reported ≥1 AE (see Table: Adverse Events in ICONIC-TOTAL through Week 52).3 
  • No new safety signals were identified through week 52.3 

Adverse Events in ICONIC-TOTAL through Week 523
Weeks 0-16
Weeks 16-52
Through Week 52
ICO (n=208)
PBO (n=103)
PBO→ICO (n=92)
ICO
(n=208)
ICO Combineda (n=300)
Mean weeks/total PYs of follow-up
16.0/63.6
15.6/30.8
36.2/63.9
49.3/196.4
45.3/260.2
Any AE, n (%)
105 (50)
46 (45)
51 (55)
153 (74)
204 (68)
SAEs, n (%)
1 (<1)
2 (2)
1 (1)
6 (3)
7 (2)
AEs leading to discontinuation, n (%)
6 (3)
4 (4)
0
7 (3)
7 (2)
Infections, n (%)
59 (28)
23 (22)
39 (42)
106 (51)
145 (48)
Serious infections, n (%)
0
1 (1)
0
0
0
Gastrointestinal AEs, n (%)
15 (7)
8 (8)
7 (8)
21 (10)
28 (9)
Malignancy,b n (%)
1 (<1)
0
0
2 (1)
2 (1)
Abbreviations: AE, adverse event; ICO, icotrokinra; PBO, placebo; SAE, serious adverse event; PY, patient-year.
aIncludes data for ICO-randomized patients through week 52 and for PBO→ICO patients from week 16 through week 52.
bMalignancy includes chronic lymphocytic leukemia and malignant melanoma in situ.

ICONIC-LEAD

Bissonnette et al (2025)2 and Soung et al (2025)4,5 evaluated the efficacy and safety of oral icotrokinra 200 mg once daily in patients ≥12 years of age with moderate to severe plaque PsO in an ongoing phase 3, multicenter, randomized, double-blind, PBO-controlled study with randomized withdrawal and retreatment.

Study Design/Methods

  • Key inclusion criteria2:
    • Age ≥12 years with moderate to severe plaque PsO diagnosed for ≥26 weeks before screening; candidate for phototherapy or systemic therapy
    • Total BSA involvement ≥10%
    • Psoriasis Area and Severity Index (PASI) score ≥12
    • IGA score ≥3
  • Patients were randomized (2:1) to receive either icotrokinra 200 mg orally once daily or PBO, with PBO crossover to icotrokinra at week 16. 
  • Coprimary endpoints: IGA 0/1 response with a ≥2-grade reduction from baseline to week 16 and PASI 90 response at week 16.
  • Select subgroup analysis outcomes: sPGA-G 0/1 and sPGA-G 0 responses among patients with a baseline sPGA-G score ≥3

Results

Patient Characteristics
  • A total of 684 patients (icotrokinra, n=456; PBO, n=228) were included in the study. Most patients were male (65%) and White (72%), with a mean age of 42.6 years.2
  • In the icotrokinra and PBO groups, respectively, 20% and 19% of patients had a sPGA-G score ≥3.4
Efficacy – Overall Population
  • Coprimary endpoints:
    • At week 16, 65% (295/456) vs 8% (19/228) of patients receiving icotrokinra vs PBO, respectively, achieved an IGA 0/1 response (treatment difference, 56.4%; 95% CI, 50.4-61.7; P<0.001).2 
    • At week 16, 50% (226/456) vs 4% (10/228) of patients receiving icotrokinra vs PBO, respectively, achieved a PASI 90 response (treatment difference, 45.1%; 95% CI, 39.5-50.4; P<0.001).2 
Efficacy - High-Impact Site Involvement Subgroup Analysis

ICONIC-LEAD Subgroup Analysis - Select High-Impact Site Response Rates4 
ICO
(n=92)
PBO
(n=44)
Treatment Difference, %
(95% CI);
P-Value
Proportion of patients achieving endpoint, %
   sPGA-G 0/1a
      Week 16
71
39
33.8 (15.7-49.6)b
Nominal P<0.001c
      Week 24
80
-
-
   sPGA-G 0a
      Week 16
58
25
34.4 (16.6-49.3)b
Nominal P<0.001c
      Week 24
70
-
-
Abbreviations: CI, confidence interval; CMH, Cochran-Mantel-Haenszel; ICO, icotrokinra; PBO, placebo;
sPGA-G, static Physician’s Global Assessment of Genitilia.
aAmong patients with a baseline sPGA-G score ≥3.
bTreatment difference and 95% CI (using Miettinen-Nurminen method) were calculated adjusting for age group and baseline weight category for adults using Mantel-Haenszel weights.
cP-values were based on CMH chi-square test stratified by age group and baseline weight category for adults. Nominal P-value <0.001 for ICO vs PBO. The endpoint was not controlled for multiple comparisons. Therefore, the P-value is nominal, and statistical significance has not been established.
Safety – Overall Population
  • Through week 16, 50% and 49% of patients in the icotrokinra and PBO groups, respectively, reported ≥1 AE, with nasopharyngitis and upper respiratory tract infections being the most common.5  
  • Through week 16, 23% (107/456) and 22% (51/228) of patients in the icotrokinra and PBO groups, respectively, reported an infection.2 
  • The icotrokinra AE profile through week 52 was consistent with that observed through week 16 (see Table: Adverse Events in the Overall ICONIC-LEAD Population through Week 52).2,5,7 

Adverse Events in the Overall ICONIC-LEAD Population through Week 522,5,7 
PBO-Controlled
(Adults and Adolescents)
Active Treatment
(Adults and Adolescents)
ICO Responders
Rerandomized at Week 24 (Adults)
Weeks 0-16
Weeks 16-52
Weeks 0-52
Weeks 24-52
ICO
(n=456)
PBO
(n=228)
ICOa
(n=213)
ICO
(n=456)
ICO→ICO (n=168)
ICO→PBOb (n=172)
Follow-up duration, weeks, mean
15.9
15.8
35.3
43.4
27.7
27.8
Any AE, n (%)
226 (50)
112 (49)
132 (62)
313 (69)
92 (55)
82 (48)
Most common AEs (≥5%)
   Nasopharyngitis,
   n (%)
31 (7)
15 (7)
23 (11)
64 (14)
21 (12)
20 (12)
   URTI, n (%)
30 (7)
16 (7)
24 (11)
52 (11)
9 (5)
15 (9)
SAE,c n (%)
6 (1)
6 (3)
4 (2)
16 (4)
3 (2)
5 (3)
Serious infection, n (%)
1 (<1)
0
1 (<1)
1 (<1)
0
1 (1)
AE leading to discontinuation,d n (%)
6 (1)
1 (<1)
4 (2)
10 (2)
1 (1)
3 (2)
Gastrointestinal AE,e n (%)
26 (6)
13 (6)
9 (4)
51 (11)
7 (4)
8 (5)
Active tuberculosis,
n (%)
0
0
0
0
0
0
Malignancy,f
n (%)
2 (<1)
0
0
2 (<1)
0
0
Abbreviations: AE, adverse event; ICO, icotrokinra; PBO, placebo; SAE, serious adverse event; SOC, System Organ Class; URTI, upper respiratory tract infection.
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, worsening psoriasis, and hypertensive urgency in the PBO group; and adenocarcinoma of the colon, prostate cancer, pancreatitis, bacterial gastroenteritis, arthralgia, and subarachnoid hemorrhage in the ICO group.
dAEs leading to discontinuation through week 16 included blood glucose increase in the PBO group; and adenocarcinoma of the colon, prostate cancer, hypertriglyceridemia, subarachnoid hemorrhage, erectile dysfunction, and psoriasis in the ICO group.
eBased on gastrointestinal disorders SOC.
fIncluded 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; this participant had an elevated prostate-specific antigen level before baseline and received a diagnosis of grade 1 prostate cancer on day 48).

Literature Search

A literature search of MEDLINE®, EMBASE®, BIOSIS Previews®, and DERWENT® (and/or other resources, including internal/external databases) was conducted on 16 January 2026.

 

References

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1 Gooderham M, Lain E, Bissonnette R, et al. Targeted oral peptide icotrokinra for psoriasis  involving high-impact sites. NEJM Evid. 2025;4(12):EVIDoa2500155.  
2 Bissonnette R, Soung J, Hebert AA, et al. Oral icotrokinra for plaque psoriasis in adults and adolescents. N Engl J Med. 2025;393(18):1784-1795.  
3 Lain E, Warren RB, Gooderham M, et al. Durability of response to the targeted oral peptide icotrokinra for high-impact site psoriasis: 1-year ICONIC-TOTAL findings. Poster presented at: Fall Clinical Dermatology Conference; October 23-26, 2025; Las Vegas, NV.  
4 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.  
5 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.  
6 Gooderham M, Lain E, Bissonnette R, et al. Supplement to: Targeted oral peptide icotrokinra for psoriasis involving high-impact sites. NEJM Evid. 2025;4(12).  
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.