Pfizer Phase II Data Supports Once-Monthly Trispecific Antibody Development

Pfizer has reported that a Phase II study of tilrekimig (PF-07275315), a trispecific antibody for moderate to severe atopic dermatitis, met its primary efficacy endpoint. The trial demonstrated a statistically significant increase in the proportion of participants achieving EASI-75—a measure of at least 75% improvement in the Eczema Area and Severity Index—at Week 16 compared with placebo, marking a key milestone in the clinical evaluation of this multi-target therapy, the company announced on March 9, 2026.¹

Tilrekimig simultaneously targets interleukin-4 (IL-4), interleukin-13 (IL-13), and thymic stromal lymphopoietin (TSLP), which are cytokines central to Type 2 (Th2) inflammatory responses. By modulating multiple immune pathways without engaging receptors on healthy cells, the antibody is designed as a once-monthly treatment candidate for chronic inflammatory conditions, including atopic dermatitis, asthma, and chronic obstructive pulmonary disease.²

“We are encouraged by the topline Phase [II] results for tilrekimig, which show that combining the potent inhibition of IL-4/13 and TSLP pathways has the potential to deliver improved efficacy over the standard of care for atopic dermatitis,” said Mike Vincent, chief Inflammation & Immunology officer, Pfizer, in a company press release.¹ “We plan to advance a broad clinical development program for tilrekimig, a potential first-in-class trispecific antibody discovered at Pfizer, in atopic dermatitis and other Th2-mediated inflammatory diseases including asthma and COPD [chronic obstructive pulmonary disease].”

What are the clinical implications of trispecific antibody therapy in atopic dermatitis?

According to the company, the Phase II study included multiple dosing levels, showing a dose-dependent response. Placebo-adjusted proportions of participants achieving EASI-75 at Week 16 were 38.7% for the lowest dose, 51.9% for the middle dose, and 49.4% for the highest dose.¹ The two higher dose levels suggest efficacy that could be competitive with currently approved biologics, offering a potential advancement in treatment options for patients who respond inadequately to existing therapies.

The company reported that tilrekimig was well-tolerated across all doses, with adverse events comparable to placebo. Common adverse events included infections, skin and subcutaneous tissue disorders, and administration site reactions. Three serious adverse events occurred but were deemed unrelated to treatment. Notably, the frequency of conjunctivitis in this study was lower than that reported for existing IL-4 receptor alpha inhibitors, indicating a potentially favorable safety profile for patients at risk of ocular side effects.¹

How is tilrekimig being evaluated across inflammatory disease indications?

The Phase II trial is a randomized, double-blind, placebo-controlled study conducted in four overlapping stages. Stage 1 assessed high-dose tilrekimig versus placebo and included an arm evaluating ompekimig, a trispecific antibody targeting IL-4, IL-13, and interleukin-33. Both antibodies met the primary efficacy endpoint in this stage. Stage 2 focused on dose-ranging for tilrekimig, while Stage 3 is examining patients with prior biologic exposure. Stage 4 continues dose-ranging evaluation for ompekimig.

In parallel, ongoing Phase II studies are investigating tilrekimig in asthma, and a Phase IIb/III study has been initiated in chronic obstructive pulmonary disease. Planning for a pivotal Phase II atopic dermatitis study is underway, with initiation expected later this year. Detailed results from the Phase II study will be submitted to a peer-reviewed journal and presented at a future scientific meeting, Pfizer stated.¹

Why is this development significant for the biopharmaceutical industry?

Atopic dermatitis affects patients globally with chronic itch, rashes, and disrupted sleep. Current treatments do not always achieve clinically meaningful responses, highlighting an unmet need for therapies capable of modulating multiple Th2 pathways. The clinical performance of tilrekimig may inform future design of multispecific biologics and represents a potential step forward in integrating multi-target immune modulation in chronic inflammatory disease management.³

References

1. Pfizer. Pfizer’s Phase 2 Study of Trispecific Antibody Positive in Moderate to Severe Atopic Dermatitis. Press Release. March 9, 2026.
2. Guttman-Yassky E, Kabashima K, Staumont-Salle D, et al. Targeting IL-13 with tralokinumab normalizes type 2 inflammation in atopic dermatitis both early and at 2 years. Allergy. 2024;79(6):1560-1572. doi: 10.1111/all.16108 
3. Faye O, Flohr C, Kabashima K, et al. Atopic dermatitis: A global health perspective. J. Eur. Acad. Dermatol. Venereol. 2023;38(5):801-811. doi: 10.1111/jdv.19723