Pfizer's Tilrekimig Shows Skin Clearance in Phase 2 Study

Pfizer Inc. (NYSE: PFE) today presented detailed results from an ongoing Phase 2 study investigating tilrekimig (PF-07275315) in adults with moderate-to-severe atopic dermatitis (AD). The study met its primary endpoint, demonstrating a statistically significant increase in the percentage of participants achieving EASI-75* (≥75% reduction in the Eczema Area and Severity Index) at Week 16 across all evaluated doses compared to placebo. The findings were shared today in an oral presentation at the 35th European Academy of Dermatology and Venereology (EADV) Annual Congress in Vienna, Austria.

Tilrekimig is an investigational, potential first-in-class trispecific antibody that simultaneously inhibits upstream and downstream drivers of type 2 inflammation through concurrent high-affinity binding to interleukin-4 (IL-4), interleukin-13 (IL-13), and thymic stromal lymphopoietin (TSLP). By directly blocking TSLP together with its downstream effectors, tilrekimig is designed to provide broader cytokine pathway coverage and potentially more durable clinical responses. Tilrekimig is also designed to have an extended half-life of about 37 days, which is anticipated to support monthly administration.

"Tilrekimig is a promising investigational medicine in Pfizer's inflammation and immunology pipeline as we seek to pursue next-generation biologics that address persistent unmet medical needs. The compelling efficacy and tolerability demonstrated in this Phase 2 study validate this multi-pathway, trispecific approach and suggest that tilrekimig has the potential to raise the bar beyond current standard-of-care biologics. Building on these promising findings, we have initiated Phase 3 trials of tilrekimig in atopic dermatitis and asthma, and we are advancing a Phase 2b/3 study in COPD."

- Michael Vincent, M.D., Ph.D., Chief Inflammation & Immunology Officer, Pfizer

"Systemic treatment in moderate-to-severe atopic dermatitis has moved from broad immunosuppression to targeted therapy, and that shift has meaningfully changed what we can offer patients. But atopic dermatitis is driven by several inflammatory signals, and a substantial proportion of patients still live with persistent itch and extensive skin involvement. The Week 16 results presented today are meaningful at this stage of development, with tilrekimig's tolerability profile supporting continued study in a larger patient population."

- Eric Simpson, M.D., M.C.R., Department of Dermatology, Oregon Health & Science University

Detailed Phase 2 Study Results at Week 16

• The ongoing Phase 2 trial is evaluating adult patients with moderate-to-severe AD. Data presented at EADV reflect the first two stages of the study, which evaluated biologic-naïve patients:
  • Stage 1 evaluated subcutaneous tilrekimig 450 mg every two weeks (Q2W) versus placebo.
  • Stage 2 was a dose-ranging evaluation of tilrekimig 400 mg, 200 mg, or 50 mg every four weeks (Q4W) versus placebo.
• The results presented at EADV build upon previously announced topline results.
• Primary Endpoint (EASI-75 at Week 16):
  • In Stage 1, 62.5% of patients receiving tilrekimig 450 mg Q2W achieved EASI-75, compared to 19.9% in the placebo group (p=0.0008).
  • In Stage 2, 58.5% (400 mg Q4W), 61.0% (200 mg Q4W), and 47.8% (50 mg Q4W) of patients receiving tilrekimig achieved EASI-75, an absolute improvement of 49.4%, 51.9%, and 38.7%, respectively, compared to 9.1% for placebo (all p<0.003).
• Key Secondary Endpoint:
  • vIGA 0/1 (Clear/Almost Clear skin with ≥2-point improvement):
    • In Stage 1, 30.3% of patients in the 450 mg Q2W group achieved vIGA 0/1 (vs 11.8% for placebo; p=0.0251)
    • In Stage 2, 26%-27% of patients across the Q4W groups achieved vIGA 0/1 (vs 0% for placebo; all p<0.006).
• Exploratory Endpoint:
  • Itch Reduction (PP-NRS4): In an exploratory analysis, greater proportions of patients receiving tilrekimig achieved a ≥4-point reduction in weekly average Peak Pruritus Numerical Rating Scale compared to placebo, with treatment differences of 35.3% (42.5% vs 7.2%) in the 400 mg Q4W group and 43.6% (50.8% vs 7.2%) in the 200 mg Q4W group.
• Safety:
  • Tilrekimig was well-tolerated, with no dose-dependent safety signals, with treatment-emergent adverse event (TEAE) rates comparable between treatment and placebo groups.
    • In Stage 1, TEAEs were reported in 46.7% of patients receiving tilrekimig 450 mg Q2W versus 28.9% of patients receiving placebo. In Stage 2, TEAEs were reported in 42.2%, 47.7%, and 47.8% of patients receiving tilrekimig 400 mg, 200 mg, and 50 mg Q4W, respectively, versus 52.2% of patients receiving placebo.
    • In doses up to 400 mg of tilrekimig Q4W, the observed frequency of conjunctivitis and injection-site reactions in this study was lower than rates reported with IL-4 receptor alpha inhibitors and comparable to placebo.
  • There were no serious adverse events related to tilrekimig in both stages 1 and 2.

About the Tilrekimig Clinical Trial Program

The Phase 2 study is an ongoing randomized, double-blind, placebo-controlled trial in adults with moderate-to-severe atopic dermatitis.

The Phase 3 pivotal program for tilrekimig is underway, with patients dosed in three Phase 3 studies: two in atopic dermatitis - including one with dupilumab as an active comparator - and one in asthma. Pfizer is also studying tilrekimig in an ongoing Phase 2b/3 study in chronic obstructive pulmonary disease (COPD).

Continuing Pfizer's Commitment to Inflammation and Immunology Conditions

These results build on Pfizer's ongoing commitment to advancing care for people living with immune-mediated skin conditions. Pfizer currently offers three approved medicines across atopic dermatitis and alopecia areata and continues to invest in a growing dermatology pipeline focused on addressing unmet needs for patients across these conditions.

Pfizer is presenting more than 30 accepted abstracts across its dermatology portfolio at the 35th EADV Congress, spanning atopic dermatitis, alopecia areata, and nonsegmental vitiligo.

• Also in atopic dermatitis, Pfizer will present a late-breaking exploratory analysis of serum protein biomarkers from the Phase 3 JADE COMPARE study of CIBINQO (abrocitinib), alongside a final integrated safety analysis of 3,850 patients with up to 6.5 years of exposure.
• In nonsegmental vitiligo (NSV), Pfizer will present Phase 3 results from the TRANQUILLO program evaluating LITFULO (ritlecitinib) as an investigational medicine in the largest Phase 3 program to date studying an oral systemic therapy in NSV.
• In alopecia areata, Pfizer plans to share long-term Phase 3 data showing clinically meaningful improvements in scalp hair regrowth with LITFULO through five years, with no new safety signals observed. Pfizer has also initiated a pivotal study evaluating LITFULO for the treatment of moderate alopecia areata.