Icotrokinra Shows Promising Results in Treating Scalp and Genital Psoriasis in Phase 3 trial

Phase 3 trial results released by Protagonist Therapeutics has revealed that icotrokinra, an oral IL-23 receptor inhibitor, achieved clear or nearly clear skin in 66% of patients with scalp psoriasis and 77% with genital psoriasis after 16 weeks of treatment.The study data was presented separately at the 2025 Society for Investigative Dermatology (SID) Annual Meeting in San Diego, CA.

The ICONIC-TOTAL study, conducted by Protagonist's collaboration partner, Johnson & Johnson, evaluated adults and adolescents 12 years of age and older with body surface area as low as 1% and at least moderate plaque psoriasis (PsO) affecting high-impact skin sites.

Key findings from the high-impact skin sites cohort of the icotrokinra ICONIC-TOTAL study [1] :

At week 16, 57% of patients treated with once daily icotrokinra achieved the study's primary endpoint with an Investigator's Global Assessment (IGA) b score of 0/1 (clear or almost clear skin) and a ≥2-grade improvement from baseline at Week 16 compared to 6% of patients receiving placebo (P<0.001).

66% of patients with scalp psoriasis achieved a scalp-specific Investigator's Global Assessment (ss-IGA) c score of 0/1 compared to 11% receiving placebo (P<0.001) at 16 weeks.

77% of patients with genital psoriasis achieved a static Physician's Global Assessment of Genitalia (sPGA-G) d score of 0/1 compared to 21% receiving placebo (P<0.001) at 16 weeks.

In the smaller subset of patients with hand/foot psoriasis, patients showed a numerically higher rate of skin clearance at Week 16 with 42% achieving a hand and/or foot Physician's Global Assessment (hf-PGA) e score of 0/1 compared to 26% receiving placebo.

Icotrokinra demonstrated a favorable safety profile. A similar proportion of patients experienced adverse events (50% and 42%) and serious adverse events (0.5% and 1.9%) in icotrokinra and placebo respectively through Week 16, with no new safety signals identified.

PN-881 represents Protagonist's next generation of oral peptides for psoriasis. Key takeaways from the pre-clinical characterization of the IL-17 oral peptide antagonist PN-881 [2] :

Exhibited nanomolar to picomolar in vitro potency comparable to bimekizumab and superior (70-fold) to secukinumab.

Showed metabolic stability in several matrices across several species, making it a suitable candidate for oral delivery.

Demonstrated PD-based target engagement in a mouse IL-17 challenge model after oral dosing

Demonstrated dose-dependent efficacy with significant reduction in skin thickness in a 5-day rat IL-23 induced skin inflammation model after oral dosing.

"High-impact skin sites affected by psoriasis can be very challenging to treat effectively and patients often experience unique challenges profoundly impacting their daily lives," said Dinesh V. Patel, Ph.D., President and Chief Executive Officer at Protagonist. "The data presented by our partner today demonstrate that icotrokinra continues to have the potential to transform the current treatment paradigm based on the impressive results achieved with a convenient targeted therapy in the form of a once-daily pill. Additionally, we are thrilled to share the first detailed characterization of our next drug candidate in the I&I space, PN-881, the first-in-class oral peptide antagonist targeting the three dimeric forms of IL-17, including AA, AF, and FF. We look forward to progressing our fully owned asset PN-881 in human clinical studies in Q4 2025."