April W. Armstrong, MD, MPH

Panelists discuss how the head-to-head ICONIC-ADVANCE studies demonstrated icotrokinra’s superior efficacy vs deucravacitinib, with approximately double the complete clearance rates and a safety profile similar to placebo.

Expert Perspectives on Key Results From ICONIC-ADVANCE 1 and 2 Trials

Patients participating in head-to-head clinical trials between icotrokinra and deucravacitinib experienced superior outcomes with the oral IL-23 receptor blocker across multiple efficacy measures. The ICONIC-ADVANCE studies enrolled adults with moderate to severe plaque psoriasis, comparing the new oral peptide against both placebo and the established TYK2 inhibitor. Patients showed consistent, reproducible responses favoring icotrokinra, with separation evident early in treatment and maintained throughout the 24-week study period.

Clinical trial participants achieved remarkable response rates with icotrokinra, including double the complete skin clearance rates compared with deucravacitinib when measuring the highest treatment bar of PASI 100 or IGA 0. Patients receiving icotrokinra demonstrated superior depth of response, with the greatest separation between treatments observed at the most stringent efficacy end points. These results represent unprecedented achievement for patients receiving oral psoriasis treatment, approaching efficacy levels typically associated with the most effective biologic therapies.

Patient safety data revealed reassuring profiles for icotrokinra, with side effects similar to placebo and lower adverse event rates compared with deucravacitinib. Infection rates were actually lower in patients receiving icotrokinra, whereas expected adverse events associated with deucravacitinib (including acne and herpes) occurred as anticipated. Patients experienced well-tolerated treatment with the oral IL-23 receptor blocker, providing confidence for individuals with moderate to severe psoriasis requiring effective oral therapy options with favorable safety characteristics.

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Panelists discuss how icotrokinra represents a novel oral peptide that selectively blocks the IL-23 receptor, offering the trusted safety profile of IL-23 inhibition in an oral formulation with high selectivity and no off-target effects.

Discussing New Data on Novel Oral Peptide for Psoriasis

Patients may soon have access to icotrokinra, an innovative oral IL-23 receptor blocker that represents a novel approach to psoriasis treatment through oral peptide delivery. This medication differs from previous IL-23-targeting biologics by specifically blocking the IL-23 receptor rather than the cytokine itself, offering patients a new mechanism of action with proven pathway targeting. The cyclic peptide form enables oral administration with improved absorption compared with traditional peptides, providing patients with convenient oral access to IL-23 pathway inhibition.

The oral peptide demonstrates high selectivity for IL-23 receptor blocking without off-target effects, giving patients precise therapeutic intervention in the key inflammatory pathway driving their psoriasis symptoms. Patients benefit from targeting the same trusted IL-23 pathway that has proven highly effective and safe in biologic treatments, now delivered through convenient oral administration. This approach combines the established safety profile of IL-23 inhibition with the patient-preferred oral delivery method.

Clinical studies reveal that patients receiving icotrokinra experience well-tolerated treatment with safety profiles similar to placebo groups. The medication targets the IL-23 inflammatory axis that patients and providers understand well from extensive biologic experience, providing confidence in the therapeutic approach. Patients appreciate accessing this proven mechanism of action through oral administration, eliminating injection-related concerns while maintaining the efficacy and safety expectations associated with IL-23 pathway targeting for psoriasis management.

Panelists discuss how second-generation PDE4 inhibitors, such as orismilast, aim to improve upon apremilast’s efficacy while maintaining safety, with phase 2 data showing PASI 75 rates up to 50%.

Expert Perspectives on Investigational PDE4 Inhibitors in Psoriasis

Patients currently benefit from apremilast as an established PDE4 inhibitor for psoriasis treatment across all severity levels, but newer agents aim to enhance efficacy while maintaining favorable safety profiles. Second-generation PDE4 inhibitors, such as orismilast, represent an advancement in oral treatment options for patients seeking improved therapeutic outcomes. These newer agents target the same trusted mechanism while striving to deliver enhanced clinical benefits for patients with moderate to severe disease.

Health care providers report comfort with the PDE4 inhibitor pathway based on extensive clinical experience and established safety data that patients can trust. The dermatology community recognizes PDE4 inhibition as a reliable therapeutic approach with well-characterized safety profiles that patients have used successfully for years. This familiarity provides confidence for both patients and providers when considering newer PDE4 inhibitor options as they become available.

Clinical trial data for orismilast demonstrate PASI 75 response rates reaching approximately 50% in phase 2 studies, representing meaningful improvement for patients compared with earlier PDE4 inhibitors. These enhanced efficacy rates suggest patients may achieve superior outcomes with next-generation PDE4 inhibitors while maintaining the safety and tolerability profiles they expect from this medication class. Patients seeking oral treatment options may benefit from these advances in PDE4 inhibitor development as new agents progress through clinical development.

Panelists discuss how emerging TYK2 inhibitors such as brepocitinib and ESK001 target the JAK/STAT pathway to block IL-23 and IL-17 signaling, showing promising phase 2 results with PASI 100 rates around 33% and PASI 75 rates of 64%.

Expert Perspectives on Investigational TYK2 Inhibitors in Psoriasis

Patients may soon benefit from next-generation TYK2 inhibitors that offer enhanced efficacy compared with current oral treatment options. Two promising molecules in late-phase development, deucravacitinib and ESK001, represent advances in targeting the JAK/STAT pathway’s inflammatory cascade central to psoriasis pathophysiology. These treatments work by blocking TYK2 through allosteric inhibition, providing high selectivity and specificity for patients seeking targeted oral therapy.

TYK2 inhibitors offer patients oral treatment that targets key inflammatory cytokines IL-23 and IL-17 through downstream signaling disruption. This mechanism allows patients to benefit from reduced signs and symptoms of psoriasis through highly selective pathway targeting. The allosteric inhibition approach provides patients with precise therapeutic intervention that minimizes off-target effects while maximizing treatment efficacy for psoriatic inflammation.

Clinical trial data demonstrate impressive efficacy rates for patients receiving investigational TYK2 inhibitors, with approximately one-third achieving complete skin clearance (PASI 100) at 12 weeks with deucravacitinib. ESK001 shows PASI 75 response rates of 64% vs 0% with placebo at week 12, representing significant advancement for patients seeking oral treatment options. These results suggest that patients may soon have access to oral medications delivering efficacy levels previously associated primarily with biologic treatments, thereby expanding convenient treatment options for moderate to severe psoriasis.

April W. Armstrong, MD, MPH

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