touchDERMATOLOGY coverage from EADV 2025:

Icotrokinra is a first-in-class, oral peptide designed to block IL-23 receptors, currently being investigated in the phase III ICONIC clinical trial program for the treatment of plaque psoriasis.

In this interview, Dr Linda Stein Gold (Henry Ford Health, Detroit, MI, USA) talks to touchDERMATOLOGY about the aims, design and findings from the ICONIC-ADVANCE 1 (NCT06143878) and ICONIC-ADVANCE 2 (NCT06220604) studies, and the impact these findings will have on clinical practice.

The abstract “Icotrokinra Demonstrated Superior Responses Compared With Placebo and Deucravacitinib in the Treatment of Moderate-to-Severe Plaque Psoriasis: Results Through Week 24 of the Phase 3 ICONIC-ADVANCE 1&2 Studies” was presented at EADV 2025, 17-20 September, Paris, France.

What is the mechanism of action of icotrokinra, and how will a once daily pill benefit patients?

Icotrokinra is an oral peptide that selectively binds the IL-23 receptor, and inhibits the downstream signalling of the IL-23 molecule. This therapy will help benefit patients as a lot of psoriasis patients actually prefer an oral medication. So if we can give them the possibility of good efficacy, good safety and good tolerability, a significant proportion of our patients would prefer to take a pill.

Could you describe the aims and design of the phase III ICONIC-ADVANCE 1&2 studies?

The ICONIC-ADVANCE 1&2 studies were phase III clinical trials with three arms, all participants were adult patients with moderate-to-severe plaque psoriasis. The first arm was ICO 200 mg once a day, the second arm was placebo, and the third arm was an active control, which was deucravacitinib at 6 mg once daily. Patients were treated for 16 weeks and there were two co-primary endpoints, IGA score of 0/1, and PASI 90 versus placebo, and at that time point the placebo patients were transitioned to ICO 200 mg daily. At week 24, we were looking at some key secondary endpoints, which included comparison of ICO with deucravacitinib.

How well were the primary and secondary endpoints met?

ICO met all of its primary and secondary endpoints when we look at achieving IGA of clear or almost clear, we see up to 70% of patients on ICO achieve that at week 16 and up to 74% at week 24. This was superior to the deucravacitinib, which got to clear or almost clear in up to 54% of patients at week 16 and up to 55% at week 24. Looking at PASI 90, again we found nice separation that occurred as early as week 8, between ICO and deucravacitinib, as well as placebo, and that separation continued over the course of the 24 weeks.

What is the safety profile of icotrokinra?

It’s important whenever we have a new drug to look at the safety. What we found in terms of the safety and the adverse event (AE) profile of ICO is that it was similar to placebo through week 16, and that there was a lower incidence of overall adverse events through week 24 compared to deucravacitinib. When we look at the infection rates, again, ICO was similar to placebo, and ICO was actually lower than deucravacitinib. Looking at the AEs of special interest, we saw a slightly higher incidence of acne and herpes in the deucravacitinib group versus the ICO group.

What are the potential impacts of this study for clinical practice?

The impact of these ICONIC-ADVANCE 1 and 2 trials are that we potentially have another option for oral therapy, and the first time we’re looking at an oral peptide for the treatment of moderate-to-severe plaque psoriasis patients. This drug is potentially fulfilling an unmet need, because we see really good efficacy, we see good tolerability, and we see a safety profile that’s similar to placebo. So I think this will potentially provide another option for our patients who prefer an oral therapy.