SUMMARY

• The company cannot recommend any practices, procedures, or usage of ICOTYDE that deviate from the approved labeling.
• Please refer to the local labeling for relevant information regarding the dosage of ICOTYDE.
• FRONTIER-1 was a phase 2b, randomized, placebo (PBO)-controlled, dose-ranging study (NCT05223868) evaluating the dose-response of ICOTYDE at week 16 in adults with moderate to severe plaque psoriasis (PsO).^1,2 FRONTIER-2 (NCT05364554) was the long-term extension of FRONTIER-1.³
• A population pharmacokinetic (PK) and exposure-response (ER) modeling analysis was conducted using integrated data from a phase 1 study (healthy participants) and a phase 2 study (patients with moderate to severe plaque PsO who received ICOTYDE) to characterize the relationship between systemic exposure to ICOTYDE and clinical response.⁴
  • At week 16, ER modeling analysis predicted that ICOTYDE 200 mg once daily (QD) and 100 mg twice daily (BID) would result in similar response rates for Psoriasis Area and Severity Index (PASI) 75, PASI 90, PASI 100, and Investigator’s Global Assessment (IGA) 0/1.

CLINICAL and pharmacokinetic DATA

Phase 2 Study - FRONTIER-1 and FRONTIER-2

FRONTIER-1 was a phase 2b, randomized, PBO-controlled, dose-ranging study designed to evaluate the dose-response of ICOTYDE in adult patients with moderate to severe plaque PsO. FRONTIER-2 was the long-term extension of FRONTIER-1.^1-3

Study Design/Methods

• Adults with a diagnosis of plaque PsO for ≥6 months who were candidates for phototherapy or systemic therapy, had a PASI score ≥12, an IGA score ≥3, and body surface area (BSA) involvement of ≥10% were eligible for enrollment.
• Eligible patients (N=255) were randomized (1:1:1:1:1:1) to 1 of 6 treatment groups including PBO and varying ICOTYDE dosages and dosing frequencies as seen in Figure: FRONTIER-1 and FRONTIER-2 Study Design.

Results

• A total of 255 patients were included in FRONTIER-1, and 89% (N=227) of those patients continued treatment in FRONTIER-2, with 35 patients in the PBO→ICOTYDE 100 mg QD group.³
• At baseline, a majority of the patients were White (75%) and male (69%). The mean duration of PsO was about 18 years and the mean PASI score was about 19. The percentage of patients with severe PsO (IGA score ≥ 4) was higher in the ICOTYDE 25 mg once-daily and 100 mg twice-daily groups vs the other groups.¹

Efficacy

• Efficacy endpoint results at weeks 16 and 52 are summarized in Table: Key Efficacy Endpoint Results at Weeks 16 and 52 (NRI).

Safety

• Through week 16, the proportion of patients experiencing ≥1 adverse events (AEs) was comparable between ICOTYDE treatment groups and the PBO group.¹
  • There were 3 serious AEs reported through week 16 that were determined to be unrelated to the trial drug by the principal investigator: coronavirus disease 2019 (COVID-19; n=1, ICOTYDE 100 mg QD), infected cyst (n=1, ICOTYDE 50 mg QD), and a suicide attempt (n=1, ICOTYDE 100 mg QD).
  • There was no evidence of dose-dependent increase in occurrence of AEs or serious AEs across the ICOTYDE treatment groups.
• From week 16 through week 56, 58.6% (133/227) of patients experienced ≥1 AE.³
  • 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.

Bozenhardt et al (2025)⁴ conducted population PK and ER modeling analyses using data from phase 1 (healthy patients) and phase 2 studies (patients with moderate to severe plaque PsO) to characterize the relationship between systemic exposure to ICOTYDE and clinical response.

Study Design/Analyses

• Data were collected from the phase 2b FRONTIER-1 and FRONTIER-2 studies, which informed dose selection for phase 3 trials.
• Population PK analyses were conducted using integrated data from phase 1 (healthy patients) and phase 2 studies (FRONTIER-1 and FRONTIER-2).
  • PK data were described using a one-compartment model with first-order absorption and linear elimination. The relationship between clinical response and population PK-predicted average concentration (C_avg) was modeled using ordinal logistic regression.
• The ER analyses dataset included individual PK exposure metrics and PASI/IGA data from 231 patients, including those who received PBO.
  • As the PBO group was not maintained after week 16, PBO response rates at week 16 were extrapolated to weeks 24 and 52.
  • Observed and model-predicted, PBO-corrected response rates were plotted against C_avg at steady-state concentration (C_avg,ss).

Results

• Overall exposures between ICOTYDE 200 mg QD and 100 mg BID were reported to be similar at steady state.
• At week 16, ER modeling analysis predicted that ICOTYDE 200 mg QD and 100 mg BID would achieve similar response rates for PASI 75, PASI 90, PASI 100, and IGA 0/1.
• Model-predicted PBO-corrected PASI and IGA maximal response rates were expected to be maintained or increased from week 16 to week 24 and week 52.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 04 February 2026.