ICOTYDE - Treatment of Genital Psoriasis

SUMMARY

• The company cannot recommend any practices, procedures, or usage of ICOTYDE that deviate from the approved labeling.
• The safety and efficacy of ICOTYDE 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 across these studies.^1-4
  • In ICONIC-TOTAL, at week 16, 77% vs 21% of patients in the ICOTYDE vs placebo (PBO) groups 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).^1,2 At week 52, 85% of patients in the ICOTYDE group achieved an sPGA-G 0/1 response.⁵ 
    • At week 16, 62% vs 10% of patients in the ICOTYDE vs PBO groups achieved an sPGA-G 0 response.^1,2 At week 52, 73% vs 86% of patients in the ICOTYDE vs PBO→ICO groups achieved an sPGA-G 0 response.⁵
  • In a pooled analysis of 4 phase 3 trials, sPGA-G 0/1 response rates were 76% with ICOTYDE and 29% with PBO at week 16, and 84% with ICOTYDE and 79% with PBO→ICOTYDE at week 24.³

CLINICAL DATA

ICONIC-TOTAL

Warren et al (2026)⁵, Gooderham et al (2025),¹ and Lain et al (2025)² evaluated the efficacy and safety of oral ICOTYDE 200 mg once daily in patients ≥12 years of age with plaque PsO and at least moderate high-impact site involvement (scalp, genitals, and/or hands/feet) in an ongoing phase 3, multicenter, randomized, double-blind, PBO-controlled study.

Study Design/Methods

• Key inclusion criteria^1,5
  • Adults (≥18 years) and adolescents (≥12 to <18) with plaque PsO diagnosed for
    ≥26 weeks at screening; candidate for phototherapy or systemic therapy with an inadequate response to ≥1 topical therapy
  • Total body surface area (BSA) involvement ≥1% and an Investigator’s Global Assessment (IGA) score ≥2
  • Involvement of ≥1 high-impact site with at least moderate severity (scalp-specific Investigator’s Global Assessment [ss-IGA] score ≥3, sPGA-G score ≥3, Physician’s Global Assessment of hands and feet [hf-PGA] score ≥3)
• Patients were randomized (2:1) to receive oral ICOTYDE 200 mg or PBO once daily, with PBO crossover to ICOTYDE at week 16 and active treatment through week 156.^1,5 
• Primary and select key secondary outcome measures are described in Table: Select ICONIC-TOTAL Outcome Measures at Week 16.

Results

Patient Characteristics

• A total of 311 patients (ICOTYDE, n=208; PBO, n=103) were included in the study.⁵ 
• A total of 275 patients (88%) completed the 52-week treatment period, 184 (88%) of whom were randomized to ICOTYDE. Of the 92 patients randomized to PBO who transitioned to ICOTYDE at week 16, 91 (99%) completed the 52-week treatment period.⁵ 
• A total of 200 patients (64%) were male and 243 (78%) were White. The mean (standard deviation) age was 44.7 (14.3) years (6 patients [2%] were adolescents).^1,5
• In the ICOTYDE 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% (ICOTYDE, 75/98) vs 69% (PBO, 29/42)
  • Severe genital PsO: 22.4% (ICOTYDE, 22/98) vs 28.6% (PBO, 12/42)
  • Very severe genital PsO: 1.0% (ICOTYDE, 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 ICOTYDE vs PBO, respectively, achieved an IGA 0/1 response (adjusted treatment difference, 51.1%; 95% CI, 42.1-58.8; P<0.001).¹  
• The percentage of patients with genital PsO who achieved sPGA-G 0/1 response through week 52 is presented in Figure: sPGA-G 0/1Response Rates through Week 52.
• Among 75 patients who achieved sPGA-G 0/1 at week 16 with ICOTYDE, 89% sustained the response at week 52.⁵ 
• Other select endpoints are described in Table: Other Select ICONIC-TOTAL Endpoints through Week 52.

Overall Safety

• Through week 16, the most common adverse events (AEs; ≥5% of patients in any group) were nasopharyngitis (ICOTYDE, 12%; PBO, 11%), upper respiratory tract infection (ICOTYDE, 4%; PBO, 5%), and headache (ICOTYDE, 3%; PBO, 6%.⁵ 
• Through week 52, the ICOTYDE safety profile was comparable with that observed through week 16.
• No new safety signals were identified through week 52. For more details, see Table: AEs in ICONIC-TOTAL through Week 52.^2,5 

Pooled Analyses of Phase 3 Studies

Soung et al (2026)³ evaluated the effects of ICOTYDE in a pooled cohort of patients with PsO involving high-impact sites, including the scalp, genitals, hands/feet, and/or nails, across 4 phase 3 studies (ICONIC-LEAD, ICONIC-TOTAL, ICONIC-ADVANCE 1, and ICONIC- ADVANCE 2; N=1866).

Study Design/Methods 

• For the study design of ICONICTOTAL (N=311), please refer to the relevant section above.
• ICONIC-LEAD (N=684) enrolled patients aged ≥12 years with moderate to severe plaque PsO, defined as BSA ≥10%, Psoriasis Area and Severity Index (PASI) ≥12, and IGA ≥3. Patients were randomized 2:1 to oral ICOTYDE 200 mg once daily or PBO, with PBO crossover at week 16.
• ICONIC-ADVANCE 1 (N=467) and ICONIC-ADVANCE 2 (N=404) had the same inclusion criteria as ICONIC-LEAD but enrolled only adult patients. The pooled analysis included patients randomized to ICOTYDE or PBO (ADVANCE 1, 2:1; ADVANCE 2, 4:1), with PBO crossover at week 16.
• Select outcome: sPGA-G 0/1 and sPGA-G 0 response rates through week 24.

Results 

Patient Characteristics

• At baseline, an sPGA-G score ≥3 was observed in 26% of patients receiving ICOTYDE (n=334/1297) and in 24% of those receiving PBO (n=139/569).
• Moderate genital PsO (sPGA-G score 3): ICOTYDE, 75%; PBO, 68%
• Severe genital PsO (sPGA-G score 4): ICOTYDE, 23%; PBO, 29%
• Very severe genital PsO (sPGA-G score 5): ICOTYDE, 2%; PBO, 3%
• For baseline characteristics, see Table: Baseline Characteristics of Patients with sPGA-G score ≥3.

Efficacy

• Proportion of patients demonstrating rates of clearance through week 16:
  • sPGA-G 0/1: ICOTYDE, 76% and PBO, 29%
  • sPGA-G 0: ICOTYDE, 62% and PBO, 19%
• Proportion of patients demonstrating rates of clearance through week 24:
  • sPGA-G 0/1: ICOTYDE, 84% and PBO→ICOTYDE, 79%
  • sPGA-G 0: ICOTYDE, 73% and PBO→ICOTYDE, 58%

Safety

• Through week 16, the AE profile of ICOTYDE was similar to that of PBO in patients with at least moderate high-impact site PsO. See Table: Pooled Safety in Patients with at Least Moderate High-Impact Site PsO through Week 16.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 08 June 2026.