Tilrekimig Meets EASI-75 Goal in Atopic Dermatitis, With Eric Simpson, MD

Tilrekimig (PF-07275315), an investigational trispecific antibody against interleukin (IL)-4, IL-13, and thymic stromal lymphopoietin (TSLP), achieved EASI-75 in up to 63% of biologic-naive adults with moderate to severe atopic dermatitis at week 16 in phase 2 data presented at the European Academy of Dermatology and Venereology (EADV) Congress 2026 in Vienna.¹^,2

The molecule pairs the IL-4/IL-13 pathway blockade of dupilumab (Dupixent) with inhibition of TSLP, an upstream target already validated in asthma.¹ Pfizer has since moved tilrekimig into phase 3 development in atopic dermatitis, including a trial with dupilumab as an active comparator.³

“It's a trispecific molecule, so it binds 3 different cytokines at the same time," said Eric Simpson, MD, MCR, of the department of dermatology at Oregon Health & Science University, in Portland. "I think this is the first time we've seen public data of a bispecific or trispecific in atopic dermatitis."

Simpson, the study's lead author, spoke with HCPLive at the congress about the interim findings, the gap between skin-clearance endpoints, and what remains unknown ahead of larger trials.

Tilrekimig EASI-75 Response and Dose Findings at Week 16

The ongoing randomized, double-blind, placebo-controlled phase 2 trial enrolled biologic-naive adults with moderate to severe atopic dermatitis and a baseline EASI score of ≥ 16.¹ In stage 1, patients received subcutaneous tilrekimig 450 mg (n = 41) or placebo (n = 20) every 2 weeks. In stage 2, patients received tilrekimig 400 mg (n = 41), 200 mg (n = 41), 50 mg (n = 23), or placebo (n = 22) every 4 weeks through week 16.¹

The primary endpoint was the proportion of patients achieving EASI-75 at week 16. In stage 1, 63% of patients receiving tilrekimig 450 mg achieved EASI-75 compared with 20% receiving placebo (treatment difference, 43%; P =.0008).¹ In stage 2, EASI-75 rates reached 59%, 61%, and 48% with the 400 mg, 200 mg, and 50 mg doses, respectively, versus 9% with placebo (treatment differences, 50%, 52%, and 39%; all P <.003).¹

Simpson described a partial dose response across the monthly regimens. The 2 top doses produced the strongest and most similar efficacy, and the 50 mg dose trailed both, he said.

Placebo-Adjusted vIGA and Tilrekimig Safety Profile

For the key secondary endpoint of a validated Investigator's Global Assessment (vIGA) score of 0/1 with ≥ a 2-point improvement, 30% of stage 1 patients receiving tilrekimig responded versus 12% with placebo (P =.0251).¹ Across stage 2 dose groups, 26% to 27% of patients achieved vIGA 0/1 versus 0% with placebo (all P <.006).¹

Simpson acknowledged the vIGA response rates fell well below the EASI-75 results at every dose. He encouraged clinicians to focus on the placebo-adjusted effect size, noting the placebo-adjusted vIGA delta did not necessarily exceed those of currently available biologics, though trial populations differ. Whether additional dosing could widen the delta remains an open question, he said.

In an exploratory analysis, 43% and 51% of patients receiving the 400 mg and 200 mg monthly doses achieved ≥ a 4-point reduction in the weekly average Peak Pruritus Numerical Rating Scale (PP-NRS) score, compared with 7% with placebo.¹ Tilrekimig was well tolerated, with no dose-dependent safety signals and an adverse event frequency comparable to placebo.¹

No conjunctivitis signal emerged in the study, a departure from the dupilumab experience, according to Simpson. If larger trials confirm the finding, it could suggest TSLP blockade offers some protective effect, he said.

"It's always important to look at safety with a new mechanism of action," said Simpson. "Those targets are validated in atopic dermatitis and seem safe."

Editor’s note: Reported disclosures for Simpson include GENZYME CORPORATION, PFIZER INC., Roche Products Limited, Regeneron Pharmaceuticals, Inc., Galderma Laboratories, L.P., Amgen Inc., LEO Pharma Inc., Janssen Biotech, Inc., Incyte Corporation, Hoffmann-La Roche Limited, Organon LLC, and Janssen Biotech, Inc.

References

1. Simpson E, Tan J, Paller A, et al. Phase 2 study of novel trispecific tilrekimig (PF-07275315) in patients with moderate-severe atopic dermatitis: interim efficacy and safety results at 16 weeks. Abstract 1730. Presented at: EADV Congress 2026; September 30–October 3, 2026; Vienna, Austria.

2. Campbell P. EADV 2026: tilrekimig achieves EASI-75 across all doses in atopic dermatitis. HCPLive. Published October 1, 2026. Accessed October 8, 2026. https://www.hcplive.com/view/eadv-2026-tilrekimig-achieves-easi-75-across-all-doses-in-atopic-dermatitis

3. Pfizer. Pfizer's tilrekimig shows significant skin clearance in phase 2 atopic dermatitis study. Published October 1, 2026. Accessed October 8, 2026. https://www.businesswire.com/news/home/20260930032966/en/