Icotrokinra Demonstrates High Clearance Rates in Plaque Psoriasis | Fall Clinical Derm 2025

New long-term data of the investigational therapy icotrokinra show that it is able to achieve site-specific clear or almost clear skin in patients with plaque psoriasis, according to results of the ICONIC-TOTAL trial presented at the 2025 Fall Clinical Dermatology conference in Las Vegas.

Plaque psoriasis is a chronic autoimmune disease that results in scaly plaques on the skin that can be itchy or painful. It is the most common type of psoriasis.

“Many of the patients in my practice experience significant distress when psoriasis affects sensitive areas such as the scalp, genitals, hands, and feet,” Edward (Ted) Lain, M.D., MBA, executive director of the Austin Institute for Clinical Research in Austin, Texas, and study investigator, said in a news release.

Co-developed by Johnson & Johnson and Protagonist, icotrokinra is a first-in-class targeted oral peptide that selectively blocks interleukin (IL)-23 and its receptor, which plays a key role in the inflammatory response in plaque psoriasis.

Icotronkinra is not like other therapeutics available to treat psoriasis. Currently available therapies for psoriasis include biologics, such as J&J’s Stelara (ustekinumab), which are derived from living cells that are harvested or grown in a lab, and small molecule drugs such as Bristol Myers Squibb’s Sotyktu (deucravacitinib), which are chemically synthesized compounds.

Peptides can specifically target cell receptors with fewer off-target effects than small molecules but can be less stable than biologics. Insulin and hormones are examples of peptides that are used as therapeutics, as are the glucagon-like peptide 1 (GLP-1) therapies used to treat diabetes and obesity.

The ICONIC-TOTAL phase 3 study is evaluating adults and adolescents with at least moderate scalp, genital and/or hand/foot plaque psoriasis with ≥1% body surface area (BSA) affected. This study has enrolled 311 patients and compares once-daily icotrokinra with placebo. The primary endpoint is a 2-grade improvement in overall Investigator Global Assessment (IGA) score, a five-point scale to measure disease severity.

Through week 52, icotrokinra demonstrated high and durable rates of site-specific psoriasis clearance affecting all of these high-impact and difficult-to-treat areas of the body.

Overall response rates among patients treated with once-daily icotrokinra were maintained through week 52, with 67% of patients treated with icotrokinra achieving clear or almost clear skin and 44% achieving completely clear skin. The overall response rates were also comparable among patients who received icotrokinra for all 52 weeks and those who transitioned from placebo to icotrokinra at week 16.

Adverse event and serious adverse event rates were similar through week 52 compared with those through week 16, with no new safety signals identified.

In July 2025, J&J submitted a new drug application to the FDA for icotrokinra to treat adults and adolescents 12 years of age and older with moderate-to-severe plaque psoriasis. The application was based on data from the phase 3 ICONIC-LEAD study. In the trial, patients with plaque psoriasis were randomly assigned to either icotrokinra daily or a placebo pill. The trial enrolled 456 patients into the icotrokinra group and 228 into the placebo group.

At week 16 of the trial, 65% of those assigned to the icotrokinra group had an IGA score of 0 or 1 compared with 8% of those in the placebo group. Additionally, 50% in the icotrokinra group had a Psoriasis Area and Severity Index (PASI) 90 response compared with 4% in the placebo group. PASI 90 is another commonly used measure to assess the response to psoriasis drugs.