People with moderate-to-severe plaque psoriasis in Europe could soon gain access to the first oral medicine targeting the interleukin (IL)-23 pathway, after the European Medicines Agency’s (EMA's) Committee for Medicinal Products for Human Use backed Icotyde (icotrokinra; Janssen-Cilag International).

The recommendation covers adults and adolescents aged 12 years or older who weigh at least 40 kg and are candidates for systemic therapy. If approved by the European Commission, Icotyde would offer an oral alternative to injectable IL-23-targeting therapies for a disease in which many patients still do not experience adequate or durable control.

Mechanism and Clinical Evidence 

Icotyde is a synthetic peptide that binds selectively to the IL-23 receptor with high affinity and competitively blocks IL-23 binding. This mechanism prevents the IL-23/IL-23 receptor-dependent release of inflammatory cytokines, resulting in reduced disease severity and skin involvement.

The recommendation was based on evidence from four phase 3 studies involving nearly 2500 adults and adolescents. 

In the phase 3 ICONIC-LEAD trial, 65% of participants receiving icotrokinra achieved clear or almost clear skin compared with 8% receiving placebo at week 16. Additionally, 50% of icotrokinra-treated participants achieved at least a 90% improvement in the Psoriasis Area and Severity Index score, vs 4% with placebo.

Two other phase 3 studies, ICONIC-ADVANCE 1 and ICONIC-ADVANCE 2, showed superior clinical response rates vs both placebo and deucravacitinib. In ICONIC-ADVANCE 1, 68% of icotrokinra-treated participants achieved clear or almost clear skin compared with 11% receiving placebo and 50% receiving deucravacitinib. Similar results were observed in ICONIC-ADVANCE 2, in which 70% vs 9% and 55%, respectively, achieved this endpoint.

A fourth trial, ICONIC-TOTAL, evaluated icotrokinra in patients with psoriasis affecting high-impact sites such as the scalp, genital area, and hands and feet. A significantly greater proportion of icotrokinra-treated participants achieved clear or almost clear skin overall compared with placebo recipients. Significant improvement was seen at the scalp and genital sites specifically.

The most common side effects observed with icotrokinra were fungal infections, which occurred in 1.1% of patients. Adverse event rates were generally similar between the icotrokinra and placebo groups; nasopharyngitis and upper respiratory tract infections were the most frequently reported events.

Next Steps 

Icotyde will be available as 200-mg film-coated tablets. The medication should be initiated under the guidance and supervision of a physician experienced in diagnosing and treating plaque psoriasis.

Detailed recommendations for product use will be described in the Summary of Product Characteristics, which will be published on the EMA website in all official EU languages after the European Commission grants marketing authorization.