New Phase 3 Data on Icotrokinra Suggest Efficacy for Genital, Scalp Psoriasis

New phase 3 findings have been released by Protagonist Therapeutics, Inc., demonstrating that treatment of psoriasis with icotrokinra—an oral peptide designed to selectively inhibit the interleukin (IL)-23 receptor—led to 66% of patients with scalp psoriasis and 77% of those with genital psoriasis attaining site-specific clear or almost clear skin at the 16-week mark.1

The ICONIC program is being conducted by Johnson & Johnson and its new findings were announced on May 9, 2025.2 They were revealed at the 2025 Society for Investigative Dermatology (SID) Annual Meeting in San Diego, California.3 It is estimated that 8 million Americans and over 125 million people worldwide live with psoriasis.

“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," Dinesh V. Patel, PhD, President and Chief Executive Officer at Protagonist, said in a statement.1

Highly visible regions of the human body or sensitive skin, such as the hands, scalp, feet, and genitals, can be impacted by psoriasis and, consequently, have an amplified effect on patients’ quality of life. Investigational icotrokinra is described as the first targeted oral peptide created to selectively block the IL-23 receptor, which underpins the moderate-to-severe plaque psoriasis inflammatory response.

The drug’s potential is also noted for other IL-23-mediated conditions. In the ICONIC-TOTAL trial, investigators enrolled both adult and adolescent subjects in the age range of 12 years and older with moderate plaque psoriasis. The disease would impact at least 1% of their body surface area, and the study specifically targeted those with disease in high-impact anatomical regions.

The pivotal phase 3 ICONIC clinical program of icotrokinra had been initiated with 2 studies in 2023: ICONIC-LEAD and ICONIC-TOTAL. Key results from the high-impact site subgroup of the ICONIC-TOTAL analysis include the following:

• At the 16-week mark, 57% of those involved given the once-daily icotrokinra regimen met the study's primary endpoint, with an Investigator’s Global Assessment (IGA) score of 0 or 1 being attained along with a minimum 2-grade improvement from the point of baseline. This was compared to just 6% in the placebo arm of the trial (P < .001).
• Among individuals known to have scalp involvement, 66% attained a scalp-specific IGA (ss-IGA) score of 0 or 1 compared to only 11% in the placebo arm (P < .001).
• Among subjects with genital psoriasis, it was found that 77% attained a static Physician’s Global Assessment of Genitalia (sPGA-G) score of 0 or 1 compared to 21% with placebo (P < .001).
• Among those in a smaller cohort reporting hand and/or foot psoriasis, 42% attained a hand/foot-specific PGA (hf-PGA) score of 0 or 1, as opposed to only 26% of those on placebo.

"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,” Patel said in his statement.1

Icotrokinra was shown by the investigative team to be generally well-tolerated among those included in the analysis. Adverse events were observed by investigators in 50% of subjects in the icotrokinra cohort and 42% of subjects in the placebo cohort. Additionally, serious adverse events were seen among 0.5% of the icotrokinra arm versus 1.9% in the placebo arm through the 16-week mark, with a lack of new safety concerns.

The announcement of these findings by the company also included mention of recent preclinical data on PN-881, an oral peptide antagonist designed to block all 3 dimeric forms of IL-17. They highlight their anticipation of progression to evaluating PN-881 in human clinical studies in the fourth quarter of 2025.1

References

1. Protagonist Announces Icotrokinra Phase 3 Data on Difficult-to-Treat Scalp and Genital Psoriasis and Preclinical Data on PN-881 Presented at the Society for Investigative Dermatology Annual Meeting. Protagonist Therapeutics, Inc. May 9, 2025. https://feeds.issuerdirect.com/news-release.html?newsid=5045372166011869&symbol=PTGX.

2. Icotrokinra results show significant skin clearance in patients with difficult-to-treat scalp and genital psoriasis. Johnson & Johnson. May 9, 2025. https://www.jnj.com/media-center/press-releases/icotrokinra-results-show-significant-skin-clearance-in-patients-with-difficult-to-treat-scalp-and-genital-psoriasis.

3. Gooderham MJ, et al. Phase 3 results from an innovative trial design of treating plaque psoriasis involving difficult-to-treat, high-impact sites with icotrokinra, a targeted oral peptide that selectively inhibits the IL-23-receptor. Presented at the 2025 Society for Investigative Dermatology (Abstract #LB1142). May 2025.