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icotrokinra

Medical Information

Icotrokinra - Overview of FRONTIER 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 
  • FRONTIER-1 is a phase 2b, randomized, placebo-controlled, dose-ranging study (NCT05223868) designed to evaluate the dose-response of icotrokinra treatment at week 16 in adult patients with moderate to severe plaque psoriasis (PsO).2,3
    • At week 16, the primary endpoint of ≥75% improvement in Psoriasis Area and Severity Index (PASI 75) response was observed in 37.2% of 43 patients receiving icotrokinra 25 mg daily (QD), 51.2% of 41 patients receiving 25 mg twice daily, 58.1% of 43 patients receiving 50 mg QD, 65.1% of 43 patients receiving 100 mg QD, 78.6% of 42 patients receiving 100 mg twice daily, and 9.3% of 43 patients receiving placebo.
    • The proportion of patients experiencing 1 or more adverse events (AEs) was comparable between the icotrokinra treatment groups and the placebo group.
    • There was no evidence of dose-dependent increase in occurrence of AEs across the icotrokinra treatment groups.
  • FRONTIER-2 is a phase 2b, long-term extension (LTE) of FRONTIER-1. It was a dose-ranging study (NCT05364554) that evaluated the dose-response of icotrokinra treatment from week 16 to 52 in adult patients with moderate to severe plaque PsO.4 
    • At week 52, the primary endpoint of PASI 75 was observed in 49% (21/43) of patients receiving icotrokinra 25 mg QD, 58% (24/41) of patients receiving 25 mg twice daily, 70% (30/43) of patients receiving 50 mg QD, 65% (28/43) of patients receiving 100 mg QD, and 76% (32/42) of patients receiving 100 mg twice daily. Among the patients treated with placebo who were crossed over to receive icotrokinra 100 mg QD, 66% (23/35) of patients achieved PASI 75 at week 52.4,5 
    • No new safety signals were identified with icotrokinra treatment through week 56.4 

CLINICAL DATA

Phase 2 Study - FRONTIER-1

Bissonnette et al (2024)2 reported results from a phase 2, randomized, placebo-controlled, dose-ranging study evaluating the dose-response of icotrokinra for the treatment of moderate to severe plaque PsO.

Study Design/Methods

  • Adult patients (≥18 years of age) with a diagnosis of plaque PsO for ≥6 months prior to the first icotrokinra administration, with or without psoriatic arthritis; who were candidates for phototherapy or systemic therapy; had a baseline Psoriasis Area and Severity Index (PASI) score ≥12; baseline Investigator’s Global Assessment (IGA) score ≥3; and baseline body surface area (BSA) ≥10% were eligible for enrollment.2
  • Excluded patients included: patients with nonplaque form of PsO; drug-induced PsO; previously received other agents targeting IL-23; received any therapeutic agent targeting IL-17 receptor or IL-12/23 receptor, anti-tumor necrosis factor (TNF) alpha, T-cell modulators, or an experimental antibody within 12 weeks or 5 half-lives, whichever is longer, of the first administration of icotrokinra; received agents that deplete B cells (including, but not limited to, rituximab, or alemtuzumab) within 26 weeks, of the first administration of icotrokinra.3
  • Eligible patients (N=255) were randomized in a 1:1:1:1:1:1 ratio to 1 of 6 treatment arms2:
    • Icotrokinra 25 mg oral (PO) QD (n=43)
    • Icotrokinra 25 mg PO twice daily (n=41)
    • Icotrokinra 50 mg PO QD (n=43)
    • Icotrokinra 100 mg PO QD (n=43)
    • Icotrokinra 100 mg PO twice daily (n=42)
    • Placebo (n=43)
  • The primary endpoint was the proportion of patients achieving PASI 75 response at week 16.2
  • AEs and serious AEs were measured through week 24.2

Results

Patient Characteristics

Demographics and Disease Characteristics at Baseline (Full Analysis Set)2,6
Icotrokinra
Placebo
Total
25 mg QD
25 mg BID
50 mg QD
100 mg QD
100 mg BID
n=43
n=41
n=43
n=43
n=42
n=43
N=255
Age, years, mean (SD)
44.5 (12.72)
45.7 (11.91)
45.1 (11.08)
44.7 (14.11)
42.0 (11.34)
43.9 (14.70)
44.3
(12.65)
Weight, kg, mean (SD)
89.0 (19.42)
90.8 (22.12)
87.6 (19.23)
85.4 (22.49)
88.5 (16.94)
92.1 (24.66)
88.9
(20.87)
PsO disease duration, years, mean (SD)
15.5 (11.76)
18.1 (11.82)
21.5 (11.16)
19.5 (13.34)
16.7 (13.78)
17.9 (14.37)
18.2
(12.79)
PASI total score, mean (SD)
18.90 (5.27)
18.46 (5.84)
19.23 (5.08)
18.42 (6.87)
20.33 (6.51)
18.99 (5.34)
19.05
(5.83)
IGA score, n (%)
Severe (4)
13 (30)
8 (20)
7 (16)
8 (19)
12 (29)
5 (12)
53 (21)
Moderate (3)
30 (70)
33 (80)
36 (84)
35 (81)
30 (71)
38 (88)
202 (79)
BSA, %, mean (SD)
21.1
(9.28)
20.9 (11.93)
23.9 (13.59)
20.5 (13.69)
24.2 (12.55)
26.1 (15.72)
22.8 (12.99)
Previous treatments, n (%)
Phototherapya
17 (40)
15 (37)
24 (56)
21 (49)
14 (33)
19 (44)
110 (43)
Conventional
nonbiologic
systemicb
20 (47)
20 (49)
21 (49)
24 (56)
20 (48)
17 (40)
122 (48)
Nonconventional
nonbiologic
systemicc
5 (12)
2 (5)
2 (5)
2 (5)
3 (7)
4 (9)
18 (7)
Biologicsd
7 (16)
13 (32)
11 (26)
9 (21)
9 (21)
7 (16)
56 (22)
Systemicse
33 (77)
33 (80)
35 (81)
34 (79)
31 (74)
34 (79)
200 (78)
ss-IGA score, n (%)
n=43
n=40
n=43
n=43
n=41
n=43
n=253
Severe (4)
7 (16.3)
2 (5.0)
6 (14.0)
7 (16.3)
8 (19.5)
5 (11.6)
35 (13.8)
Moderate (3)
23 (53.5)
24 (60.0)
25 (58.1)
24 (55.8)
22 (53.7)
24 (55.8)
142 (56.1)
Mild (2)
7 (16.3)
6 (15.0)
9 (20.9)
9 (20.9)
6 (14.6)
6 (14.0)
43 (17.0)
Very mild (1)
1 (2.3)
0
1 (2.3)
0
2 (4.9)
2 (4.7)
6 (2.4)
Absence (0)
5 (11.6)
8 (20.0)
2 (4.7)
3 (7.0)
3 (7.3)
6 (14.0)
27 (10.7)
Abbreviations: BID, twice daily; BSA, body surface area; IGA, Investigator’s Global Assessment; PASI, Psoriasis Area and Severity Index; PsO, psoriasis; PUVA, Psoralen plus ultraviolet A; QD, daily; SD, standard deviation; ss-IGA, scalp-specific Investigator’s Global Assessment; UVB, ultraviolet B.
aIncludes PUVA or UVB.
bIncludes PUVA, methotrexate, cyclosporine, acitretin, azathioprine.cIncludes apremilast, deucravacitinib, and tofacitinib.dIncludes etanercept, infliximab, adalimumab, ustekinumab, briakinumab, secukinumab, ixekizumab, brodalumab, guselkumab, risankizumab, tildrakizumab, alefacept, efalizumab, natalizumab, certolizumab pegol.
eIncludes conventional nonbiologic systemics, novel nonbiologic systemics, 1,25-vitamin D3 and analogues, phototherapy, biologics.
Efficacy

Efficacy Endpoints at Week 16 (Full Analysis Set, NRI)2
Icotrokinra
Placebo
25 mg QD
25 mg BID
50 mg QD
100 mg QD
100 mg BID
n=43
n=41
n=43
n=43
n=42
n=43
Proportion of patients achieving:
PASI 75a,b,n (%)
16 (37)
21 (51)
25 (58)
28 (65)
33 (79)
4 (9)
   Treatment
   differencec,
   % (95% CI)
28
(11, 45)
42
(24, 59)
49
(32, 66)
56
(39, 72)
69
(55, 84)
-
P-valued
<0.001
PASI 90,n (%)
11 (26)
11 (27)
22 (51)
20 (47)
25 (60)
1 (2)
PASI 100,n (%)
5 (12)
4 (10)
11 (26)
10 (23)
17 (40)
0
IGA 0/1,n (%)
17 (40)
21 (51)
25 (58)
27 (63)
27 (64)
5 (12)
IGA 0,n (%)
7 (16)
6 (15)
15 (35)
12 (28)
19 (45)
0
DLQI 0/1e,n (%)
12 (28)
12 (30)
16 (37)
24 (56)
18 (44)
1 (2)
PSSD symptoms score 0f,n (%)
7 (16)
7 (17)
10 (24)
12 (28)
11 (26)
0
PSSD signs score 0f,n (%)
1 (2)
4 (10)
6 (14)
7 (16)
6 (14)
0
Change from baseline to week 16 in:
PASI total score, LSM (95% CI)
-11.9
(-14.0, -9.8)
-12.9
(-15.0, -10.8)
-14.3
(-16.4, -12.2)
-14.3
(-16.4, -12.2)
-16.5
(-18.6, -14.4)
-3.7
(-5.7, -1.6)
   LSM differencec
   (95% CI)
-8.3
(-11.2, -5.3)
-9.2
(-12.2, -6.3)
-10.6
(-13.6, -7.7)
-10.7
(-13.6, -7.7)
-12.8
(-15.8, -9.9)
-
BSA, LSM (95% CI)
-12.0
(-15.2, -8.7)
-14.2
(-17.4, -11.0)
-14.6
(-17.8, -11.4)
-16.1
(-19.3, -13.0)
-20.1
(-23.3, -16.8)
-0.8
(-4.0, 2.4)
   LSM differencec
   (95% CI)
-11.2
(-15.7, -6.6)
-13.4
(-18.0, -8.8)
-13.8
(-18.3, -9.3)
-15.3
(-19.9, -10.8)
-19.2
(-23.8, -14.7)
-
PSSD signs score, LSM (95% CI)
-31.7
(-38.7, -24.8)
-40.9
(-47.8, -34.0)
-42.9
(-49.7, -36.1)
-45.3
(-52.1, -38.5)
-50.6
(-57.5, -43.7)
-7.8
(-14.6, -0.9)
   LSM differencec
   (95% CI)
-24.0
(-33.7, -14.2)
-33.1
(-42.8, -23.4)
-35.1
(-44.8, -25.5)
-37.5
(-47.2, -27.9)
-42.8
(-52.6, -33.1)
-
PSSD symptoms score, LSM (95% CI)
-27.9
(-34.6, -21.2)
-32.6
(-39.3, -25.9)
-35.3
(-41.8, -28.7)
-36.7
(-43.3, -30.0)
-40.1
(-46.8, -33.4)
-4.2
(-10.8, 2.4)
   LSM differencec
   (95% CI)
-23.7
(-33.2, -14.2)
-28.4
(-37.8, -19.0)
-31.1
(-40.4, -21.7)
-32.5
(-41.8, -23.1)
-35.9
(-45.4, -26.5)
-
Abbreviations: BID, twice daily; BSA, body surface area; CI, confidence interval; DLQI, Dermatology Life Quality Index; IGA, Investigator’s Global Assessment; LSM, least squares mean; MCP-Mod, multiple comparison procedures with modeling techniques; MMRM, mixed model for repeated measures; NRI, nonresponder imputation; PASI, Psoriasis Area and Severity Index; PASI 75/90/100, ≥75/90/100% improvement in Psoriasis Area and Severity Index response; PsO, psoriasis; PSSD, Psoriasis Symptoms and Signs Diary; QD, daily.
aPatients who discontinued treatment due to lack of efficacy/worsening of PsO or who initiated a prohibited PsO treatment were considered nonresponders after the occurrence. Patients with missing data were considered nonresponders.
bPrimary endpoint.
cCompared with placebo; LSM and LSM differences were based on the MMRM model with treatment group, visit, treatment group by visit interaction, baseline weight category (≤90 kg vs >90 kg), baseline weight category by visit interaction, baseline PASI total score, and baseline PASI total score by visit interaction as covariates.
dMCP-Mod was used to determine if a dose-response relationship was observed with icotrokinra.
eAmong patients with DLQI score ≥1 at baseline.
fAmong patients with PSSD score ≥1 at baseline.

Scalp PsO Results Among Patients with Baseline ss-IGA≥2 at Week 166
Icotrokinra
Placebo
25 mg
QD
25 mg
BID
50 mg
QD
100 mg
QD
100 mg BID
n=37
n=32
n=40
n=40
n=36
n=35
Proportions of patients, %
ss-IGA 0/1 and ≥2-grade improvement from baseline
32.4
65.6
70.0
67.5
75.0
11.4
ss-IGA 0 and ≥2-grade improvement from baseline
32.4
43.8
57.5
50.0
69.4
2.9
Abbreviations: BID, twice daily; PsO, psoriasis; QD, daily; ss-IGA, scalp-specific Investigator’s Global Assessment.
aPatients who discontinued treatment due to lack of efficacy/worsening of PsO or who initiated a prohibited PsO treatment were considered nonresponders after the occurrence. Patients with missing data were considered nonresponders.
Safety
  • The proportion of patients experiencing 1 or more AEs was comparable between icotrokinra treatment groups and the placebo group.2
  • Treatment-emergent adverse events (TEAEs) through week 16 are described in Table: Number of Patients with At Least 1 TEAEa with Frequency of ≥5% of Preferred Terms through Week 16.
  • There were 3 serious AEs reported that were unrelated to the trial drug by the principal investigator: coronavirus disease 2019 (COVID-19; n=1, icotrokinra 100 mg QD), infected cyst (n=1, icotrokinra 50 mg QD), and a suicide attempt (n=1, icotrokinra 100 mg QD).2
  • There was no evidence of dose-dependent increase in occurrence of AEs or serious AEs across the icotrokinra treatment groups.2

Number of Patients with At Least 1 TEAEa with Frequency of ≥5% of Preferred Terms through Week 162,a
Icotrokinra
Placebo
25 mg QD
25 mg BID
50 mg QD
100 mg QD
100 mg BID
Safety analysis set, n
43
41
43
43
42
43
Average follow-up duration, weeks
15.7
16.2
15.8
16.1
15.8
15.0
Patients with ≥1 AEb
20 (47)
20 (49)
26 (60)
19 (44)
26 (62)
22 (51)
Infections and infestations
15 (35)
14 (34)
17 (40)
7 (16)
11 (26)
12 (28)
   COVID-19
5 (12)
8 (20)
3 (7)
3 (7)
4 (10)
5 (12)
   Nasopharyngitis
1 (2)
3 (7)
8 (19)
1 (2)
2 (5)
2 (5)
   URTI
3 (7)
0
0
0
2 (5)
1 (2)
GI disorders
3 (7)
4 (10)
6 (14)
4 (9)
7 (17)
5 (12)
   Diarrhea
2 (5)
2 (5)
4 (9)
1 (2)
1 (2)
1 (2)
Nervous system disorders
0
2 (5)
3 (7)
3 (7)
2 (5)
1 (2)
   Headache
0
1 (2)
1 (2)
3 (7)
1 (2)
1 (2)
Respiratory, thoracic and mediastinal disorders
1 (2)
0
1 (2)
3 (7)
2 (5)
1 (2)
   Cough
1 (2)
0
1 (2)
3 (7)
1 (2)
0
Data shown are n (%) unless otherwise noted.
Abbreviations: AE, adverse event; BID, twice daily; COVID-19, coronavirus disease 2019; GI, gastrointestinal; QD, daily; TEAE, treatment-emergent adverse event; URTI, upper respiratory tract infection.
aThe safety analysis set included the same patients as the full analysis set.bAEs with an incidence of at least 5% (on the basis of the preferred term) in any trial group through the end of the trial are shown.

Phase 2 Study – FRONTIER-2

Ferris et al (2025)4 reported the LTE efficacy and safety results of icotrokinra from a phase 2b dose-ranging study (N=227) for the treatment of moderate to severe plaque PsO from week 16 through week 52.

Study Design/Methods

  • Patients randomized to an icotrokinra dosing group in FRONTIER-1 continued treatment with the same dose through week 52.4 
  • Patients randomized to the placebo group in FRONTIER-1 were crossed over to icotrokinra 100 mg QD from week 16 to 52.4 
  • Patients entered a 4-week safety follow-up period after receiving the last study treatment at week 52.4 
  • The primary endpoint was the proportion of patients achieving a PASI 75 response at week 52.4 
  • Secondary endpoints at week 52 included the proportion of patients achieving the following4:
    • ≥90% improvement from baseline PASI (PASI 90)
    • 100% improvement from baseline PASI(PASI 100)
    • IGA 0/1
    • IGA 0
    • Dermatology Life Quality Index (DLQI) score of 0/1
    • Psoriasis Symptoms and Signs Diary (PSSD) sign or symptom score of 0 (among those with a baseline score ≥1) and change from baseline in the PASI, PSSD sign score, or PSSD symptom score
    • ≥4-point reduction in the PSSD itch or pain score
  • The exploratory endpoint included the proportion of patients achieving a scalp-specific (ss)-IGA 0/1 with a ≥2-grade improvement from baseline.4 
  • Safety was evaluated through week 56 in patients who entered the LTE and received ≥1 dose of icotrokinra treatment. The frequency and type of AEs and serious AEs were measured through week 56.4 

Results

  • A total of 255 patients were included in FRONTIER-1 and 89% (227) of those patients continued treatment in FRONTIER-2 with 35 patients in the PBO→icotrokinra 100 mg QD group.6
Efficacy

Key Efficacy Endpoint Results at Week 165 
Icotrokinra
PBO
25 mg
QD
25 mg
BID
50 mg
QD
100 mg
QD
100 mg
BID
PASI, N
43
41
43
43
42
43
   PASI 75, n (%)a
16 (37)
21 (51)
25 (58)
28 (65)
33 (79)
4 (9)
   PASI 90, n (%)a
11 (26)
11 (27)
22 (51)
20 (47)
25 (60)
1 (2)
   PASI 100, n (%)a
5 (12)
4 (10)
11 (26)
10 (23)
17 (40)
0
Change in PASI from BL, N
43
41
43
43
42
43
   LSM change (95% CI)b
-11.9
(-14.0 to
-9.8)
-12.9
(-15.0 to
-10.8)
-14.3
(-16.4 to
-12.2)
-14.3
(-16.4 to
-12.2)
-16.5
(-18.6 to
-14.4)
-3.7
(-5.7 to
-1.6)
Percent change in PASI from BL, N
37
40
41
42
39
40
   LSM change (95% CI)
-59.9
(-70.2 to
-49.7)
-66.4
(-76.6 to
-56.2)
-75.8
(-85.9 to
-65.7)
-74.2
(-84.3 to
-64.2)
-84.3
(-94.6 to
-74.0)
-19.6
(-29.8 to
-9.4)
IGA, N
43
41
43
43
42
43
   IGA 0/1, n (%)a
17 (40)
21 (51)
25 (58)
27 (63)
27 (64)
5 (12)
   IGA 0, n (%)a
7 (16)
6 (15)
15 (35)
12 (28)
19 (45)
0
ss-IGA, Nc
37
32
40
40
36
35
   ss-IGA 0/1, n (%)a
12 (32)
21 (66)
28 (70)
27 (68)
27 (75)
4 (11)
   ss-IGA 0, n (%)a
12 (32)
14 (44)
23 (58)
20 (50)
25 (69)
1 (3)
DLQI, Nd
43
40
43
43
41
41
   DLQI 0/1, n (%)
12 (28)
12 (30)
16 (37)
24 (56)
18 (44)
1 (2)
PSSD symptom score, Ne
43
41
42
43
42
43
   Score 0, n (%)a
7 (16)
7 (17)
10 (24)
12 (28)
11 (26)
0
PSSD sign score, Ne
43
41
43
43
42
43
   Score 0, n (%)a
1 (2)
4 (10)
6 (14)
7 (16)
6 (14)
0
PSSD itch score, Ne
39
39
41
38
36
38
   Patients with CMI,
   n (%)a,f
20 (51)
20 (51)
27 (66)
24 (63)
30 (83)
8 (21)
PSSD pain score, Ne
34
23
27
20
33
26
   Patients with CMI,
   n (%)a,f
19 (56)
16 (70)
19 (70)
16 (80)
26 (79)
7 (27)
Abbreviations: BID, twice daily; BL, baseline; CI, confidence interval; CMI, clinically meaningful improvement; DLQI, Dermatology Life Quality Index; IGA, Investigator’s Global Assessment; LSM, least squares mean; MMRM, mixed model for repeated measures; PASI, Psoriasis Area and Severity Index; PASI 75/90/100, ≥75/90/100% improvement in Psoriasis Area and Severity Index response; PBO, placebo; PsO, psoriasis; PSSD, Psoriasis Symptoms and Signs Diary; QD, daily; ss-IGA, scalp-specific IGA.
aPatients who discontinued the study agent due to lack of efficacy/worsening of PsO or who initiated a prohibited PsO treatment were considered to be nonresponders after the event. Observed data were used for patients who discontinued study treatment. Patients with missing data were considered nonresponders.
bLSMs are based on an MMRM model with treatment group, visit, treatment group-by-visit interaction, BL weight category (≤90 kg, >90 kg), BL weight category-by-visit interaction, BL PASI total score, and BL PASI total score-by-visit interaction as covariates. Zero change was assigned after patients discontinued the study agent due to lack of efficacy/worsening of PsO or if they initiated a prohibited PsO treatment. Last observed data were used for patients who discontinued the study intervention prior to week 36 for reasons other than lack of efficacy/worsening of PsO.
cAmong patients with ss-IGA score of ≥2 at BL.
dAmong patients with a BL DLQI score of >1 at BL.
eAmong patients with a BL PSSD sign/symptoms score of ≥1.
fCMI in itch and pain scores required a ≥4-point improvement from BL among patients with BL scores of ≥4.

Key Efficacy Endpoint Results at Week 525 
Icotrokinra
PBO→
100 mg QDa
25 mg
QD
25 mg
BID
50 mg
QD
100 mg
QD
100 mg
BID
PASI, N
43
41
43
43
42
35
   PASI 75, n (%)b
21 (49)
24 (58)
30 (70)
28 (65)
32 (76)
23 (66)
   PASI 90, n (%)b
12 (28)
15 (37)
18 (42)
22 (51)
27 (64)
20 (57)
   PASI 100, n (%)b
6 (14)
7 (17)
9 (21)
11 (26)
17 (40)
12 (34)
Change in PASI from BL, N
34
36
40
35
35
34
   LSM change (95% CI)c
-12.9
(-15.0 to
-10.8)
-13.6
(-15.6 to
-11.5)
-14.3
(-16.3 to
-12.3)
-15.5
(-17.6 to
-13.5)
-17.4
(-19.5 to
-15.3)
-14.0
(-16.1 to
-11.9)
Percent change in PASI from BL, N
34
36
40
35
35
34
   LSM change (95% CI)
-65.9
(-76.6 to
-55.2)
-69.3
(-79.8 to
-58.9)
-76.8
(-86.9 to
-66.6)
-80.4
(-90.9 to
-69.8)
-90.2
(-100.8 to
-79.6)
-72.9
(-83.7 to
-62.2)
IGA, N
43
41
43
43
42
35
   IGA 0/1, n (%)b
16 (37)
19 (46)
26 (60)
26 (60)
31 (74)
23 (66)
   IGA 0, n (%)b
6 (14)
8 (20)
10 (23)
13 (30)
18 (43)
11 (31)
ss-IGA, Nd
37
32
40
40
36
28
   ss-IGA 0/1, n (%)b
18 (49)
21 (66)
27 (68)
24 (60)
27 (75)
18 (64)
   ss-IGA 0, n (%)b
15 (40)
16 (50)
23 (58)
20 (50)
24 (67)
11 (39)
DLQI, Ne
43
40
43
43
41
34
   DLQI 0/1, n (%)
11 (26)
12 (30)
18 (42)
23 (54)
23 (56)
16 (47)
PSSD symptom score, Nf
43
41
42
43
42
43
   Score 0, n (%)b
8 (19)
7 (17)
9 (21)
13 (30)
11 (26)
12 (34)
PSSD sign score, Nf
43
41
43
43
42
43
   Score 0, n (%)b
7 (16)
5 (12)
5 (12)
6 (14)
7 (17)
8 (23)
PSSD itch score, Nf
39
39
41
38
36
31
   Patients with CMI, n (%)b,g
18 (46)
18 (46)
27 (66)
23 (60)
27 (75)
17 (55)
PSSD pain score, Nf
34
23
27
20
33
22
   Patients with CMI, n (%)b,g
16 (47)
14 (61)
17 (63)
12 (60)
25 (76)
12 (54)
Abbreviations: BID, twice daily; BL, baseline; CI, confidence interval; CMI, clinically meaningful improvement; DLQI, Dermatology Life Quality Index; IGA, Investigator’s Global Assessment; LSM, least squares mean; MMRM, mixed model for repeated measures; PASI, Psoriasis Area and Severity Index; PBO, placebo; PsO, psoriasis; PSSD, Psoriasis Symptoms and Signs Diary; QD, daily; ss-IGA, scalp-specific IGA.
aOnly PBO crossover patients were included in the PBO→100 mg QD column after crossover to icotrokinra treatment.
bPatients who discontinued the study agent due to lack of efficacy/worsening of PsO or who initiated a prohibited PsO treatment were considered to be nonresponders after the event. Observed data were used for patients who discontinued study treatment. Patients with missing data were considered nonresponders.
cLSMs are based on an MMRM model with treatment group, visit, treatment group-by-visit interaction, BL weight category (≤90 kg, >90 kg), BL weight category-by-visit interaction, BL PASI total score, and BL PASI total score-by-visit interaction as covariates. Zero change was assigned after patients discontinued the study agent due to lack of efficacy/worsening of PsO or if they initiated a prohibited PsO treatment. Last observed data were used for patients who discontinued the study intervention prior to week 36 for reasons other than lack of efficacy/worsening of PsO.
dAmong patients with ss-IGA score of ≥2 at BL.
eAmong patients with a BL DLQI score of >1 at BL.
fAmong patients with a BL PSSD sign/symptoms score of ≥1.
gCMI in itch and pain scores required a ≥4-point improvement from BL among patients with BL scores of ≥4.
Safety
  • TEAEs from week 16 through week 56 are reported in Table: Patients with ≥1 TEAE with Frequency of ≥5% of Preferred Terms from Week 16 through Week 56.4 
  • From week 16 through week 56, 58.6% (133/227) of patients experienced ≥1 AE.4 
    • The most common AEs were nasopharyngitis (18.1%; 41/227), upper respiratory tract infection (9.7%; 22/227), and COVID-19 (5.3%; 12/227).
    • A dose-dependent increase was not observed in the occurrence of AEs.
  • Serious AEs were reported in 4% of patients.4 
  • No deaths were reported during LTE.4 

Patients with ≥1 TEAE with Frequency of ≥5% of Preferred Terms from Week 16 through Week 564 
Icotrokinra
PBO→
100 mg
QDb (N=35)
25 mg
QD (n=35)
25 mg
BID (n=40)
50 mg
QD (n=39)
100 mg
QD (n=40)
100 mg
BID (n=38)
Combineda
(N=227)
Mean weeks of follow-up
36.6
35.0
38.4
35.9
38.6
37.0
37.8
AEs, n (%)
18 (51.4)
27 (67.5)
19 (48.7)
27 (67.5)
19 (50.0)
133 (58.6)
23 (65.7)
Infections and
   infestations
12 (34.3)
17 (42.5)
16 (41.0)
20 (50.0)
14 (36.8)
95 (41.9)
16 (45.7)
      Nasopharyngitis
3 (8.6)
6 (15.0)
7 (17.9)
11 (27.5)
5 (13.2)
41 (18.1)
9 (25.7)
      Upper
      respiratory
      tract infection
6 (17.1)
3 (7.5)
3 (7.7)
2 (5.0)
4 (10.5)
22 (9.7)
4 (11.4)
      COVID-19
1 (2.9)
1 (2.5)
3 (7.7)
2 (5.0)
3 (7.9)
12 (5.3)
2 (5.7)
      Influenza
0
3 (7.5)
1 (2.6)
1 (2.5)
1 (2.6)
7 (3.1)
1 (2.9)
      UTI
1 (2.9)
1 (2.5)
1 (2.6)
0
2 (5.3)
7 (3.1)
2 (5.7)
      Bronchitis
1 (2.9)
1 (2.5)
3 (7.7)
0
0
6 (2.6)
1 (2.9)
      Sinusitis
0
2 (5.0)
1 (2.6)
0
0
3 (1.3)
0
Investigations
1 (2.9)
3 (7.5)
3 (7.7)
2 (5.0)
4 (10.5)
17 (7.5)
4 (11.4)
      ALT increase
1 (2.9)
0
1 (2.6)
0
2 (5.3)
6 (2.6)
2 (5.7)
      AST increase
1 (2.9)
0
1 (2.6)
0
2 (5.3)
5 (2.2)
1 (2.9)
Musculoskeletal
   and connective
   tissue disorders
0
1 (2.5)
4 (10.3)
8 (20.0)
1 (2.6)
16 (7.0)
2 (5.7)
      Arthralgia
0
0
1 (2.6)
2 (5.0)
0
4 (1.8)
1 (2.9)
GI disorders
1 (2.9)
3 (7.5)
3 (7.7)
5 (12.5)
0
13 (5.7)
1 (2.9)
      Vomiting
0
0
0
2 (5.0)
0
2 (0.9)
0
Nervous system
   disorders
3 (8.6)
4 (10.0)
0
4 (10.0)
1 (2.6)
13 (5.7)
1 (2.9)
      Headache
2 (5.7)
3 (7.5)
0
3 (7.5)
0
8 (3.5)
0
Injury, poisoning,
   and procedural
   complications
2 (5.7)
3 (7.5)
1 (2.6)
2 (5.0)
1 (2.6)
12 (5.3)
3 (8.6)
      Meniscus injury
1 (2.9)
2 (5.0)
0
0
0
3 (1.3)
0
Vascular
   disorders
0
2 (5.0)
1 (2.6)
1 (2.5)
1 (2.6)
6 (2.6)
1 (2.9)
      Hypertension
0
2 (5.0)
1 (2.6)
1 (2.5)
1 (2.6)
6 (2.6)
1 (2.9)
   Serious AEsc,
   n (%)
0
3 (7.5)
2 (5.1)
2 (5.0)
1 (2.6)
9 (4.0)
1 (2.9)
Note: Patients were counted only once for any given event, regardless of the number of times they actually experienced the event. AEs were coded using MedDRA, version 25.1.
Abbreviations: AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BID, twice daily; COVID-19, coronavirus disease 2019; GI, gastrointestinal; MedDRA, Medical Dictionary for Regulatory Activities; PBO, placebo; QD, daily; TEAE, treatment-emergent adverse event; UTI, urinary tract infection.
aPBO crossover patients were included in the PBO→100 mg QD column only after crossover to icotrokinra treatment.
bIncludes all icotrokinra treatment columns.
cSerious AEs were defined as AEs that required hospitalization, resulted in significant disability, or were life-threatening. Serious AEs included 1 occurrence each of coronary artery disease and noncardiac chest pain (same patient in the 50 mg QD group), ventricular dysfunction (25 mg BID daily), foot deformity (50 mg QD), intervertebral disc protrusion (100 mg QD), diverticulitis (100 mg QD), ligament injury (25 mg BID), uterine leiomyoma (100 mg BID), cerebrovascular accident (PBO→100 mg QD), and tonsillar hypertrophy (25 mg BID daily)

Literature Search

A literature search of MEDLINE®, EMBASE®, BIOSIS Previews®, and DERWENT® (and/or other resources, including internal/external databases) was conducted on 19 September 2025.

References

Show
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2 Bissonnette R, Pinter A, Ferris LK, et al. An oral interleukin-23 receptor antagonist peptide for plaque psoriasis. N Engl J Med. 2024;390(6):510-521.  
3 Janssen Research & Development, LLC. A study of JNJ-77242113 in participants with moderate-to-severe plaque psoriasis (FRONTIER 1). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2025 May 25]. Available from: https://www.clinicaltrials.gov/study/NCT05223868 NLM Identifier: NCT05223868.  
4 Ferris LK, Bagel J, Huang YH, et al. FRONTIER-2: a phase 2b, long-term extension, dose-ranging study of oral JNJ-77242113 for the treatment of moderate-to-severe plaque psoriasis. J Am Acad Dermatol. 2025;92(3):495-502.  
5 Ferris LK, Bagel J, Huang YH, et al. Supplement to: FRONTIER-2: a phase 2b, long-term extension, dose-ranging study of oral JNJ-77242113 for the treatment of moderate-to-severe plaque psoriasis. J Am Acad Dermatol. 2025;92(3):495-502.  
6 Bissonnette R, Pinter A, Ferris L, et al. A phase 2, randomized, placebo-controlled, dose-ranging study of oral JNJ-77242113 for the treatment of moderate-to-severe plaque psoriasis: efficacy of overall and scalp psoriasis responses from FRONTIER 1. Oral Presentation presented at: European Academy of Dermatology and Venereology; October 11-14, 2023; Berlin, Germany.