TOPLINE

Once-monthly treatment with the investigational trispecific antibody tilrekimig was associated with high clinical response rates in people with eczema, including itch improvement.

METHODOLOGY

• Tilrekimig simultaneously targets three cytokines that are important for type 2 inflammatory pathways: interleukin (IL)-4, IL-13, and thymic stromal lymphopoietin. This broad approach could be better than disease control using single cytokine-targeting therapies, such as dupilumab.
• This was a two-stage, phase 2, dose-ranging trial conducted in adults with moderate-to-severe atopic dermatitis that had not previously been treated with a biologic.
• Stage 1 compared tilrekimig given every 2 weeks (1200 mg loading dose, followed by 450 mg; n = 41) with placebo (n = 20). Stage 2 evaluated three regimens given every 4 weeks (loading/maintenance doses: 800/400 mg, n = 41; 400/200 mg, n = 41; or 100/50 mg, n = 23) vs placebo (n = 22). Treatment lasted 16 weeks, with a 20-week follow-up. Patient numbers reflect the efficacy-analysis populations.
• The primary endpoint was the proportion of patients achieving at least a 75% improvement from baseline in 75% improvement in Eczema Area and Severity Index (EASI-75) scores at week 16. Secondary endpoints included the proportion of patients achieving clear or almost clear skin with at least a 2-point improvement in the Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score (vIGA-AD score of 0/1) at week 16; the proportion achieving at least an EASI-75 score over time; and safety outcomes.

TAKEAWAYS

• EASI-75 at week 16 was achieved by significantly more tilrekimig- treated patients than placebo-treated patients in both stages of the trial, at a respective 62.5% vs 19.9% in stage 1 and 47.8%-61.0% vs 9.1% in stage 2.
• A vIGA-AD score of 0/1 was achieved by 30.3% of tilrekimig-treated patients and 11.8% of placebo-treated patients in stage 1; compared with none of the patients in the placebo arm, just over one quarter of tilrekimig-treated patients achieved this endpoint regardless of the dose.
• EASI-75 response rates were higher at week 16 than at week 8 across all tilrekimig doses.
• Achievement of at least a 4-point reduction in the Peak Pruritus Numerical Rating Scale (PP-NRS) was seen in 42.5% and 50.8% of patients who received the tilrekimig 200 mg and 400 mg maintenance doses. Significant improvement was not seen for the 50 mg maintenance dose or for placebo (8.2% and 7.2%, respectively).
• Treatment-emergent adverse events occurred in 35 of 75 tilrekimig-treated patients (46.7%) compared with 11 of 38 placebo-treated patients (28.9%) in stage 1. In stage 2, they occurred in 19/45 patients (42.2%) receiving 400 mg and 21/44 (47.8%) receiving 50 mg compared with 12/23 (52.2%) receiving placebo.
• Two patients experienced serious adverse events: angina and vomiting in one, and spontaneous abortion in the other. None of the events were considered treatment-related.
• Eye disorders were reported in three (4.0%) tilrekimig-treated patients in stage 1 vs none receiving placebo and in 4.3%-4.5% of tilrekimig-treated patients in stage 2 vs 4.3% receiving placebo. Conjunctivitis rates were numerically similar between treatment groups, while injection-site reactions were numerically less frequent with tilrekimig 400 mg every 4 weeks than with placebo.

IN PRACTICE

“We still have patients who have inadequate responses and potential adverse events to the current biologics. So there’s still a lot of development going on in atopic dermatitis, which I think rightly so,” said study investigator Eric Simpson, MD, MCR, of Oregon Health & Science University in Portland, Oregon. He told Medscape News Europe that these were the first published positive data for a dual- or triple-targeting agent in atopic dermatitis. “The fact that there was no conjunctivitis at Q4 [quarter 4] week dosing, that’s a positive thing; that’s new for the class. Whether the efficacy can be pushed higher with longer dosing might be the biggest question for phase 3.”

SOURCE

Oral presentation given during a late-breaking news session on October 1 here at the European Academy of Dermatology and Venerology (EADV) 2026 Congress in Vienna, Austria.

LIMITATIONS

This was an early-phase clinical study and as such included a small number of participants. PP-NRS was an exploratory tertiary endpoint.

DISCLOSURES

The study was funded by Pfizer. Simpson reported receiving grant and research support and personal fees from Pfizer among many other pharmaceutical companies.