Sanofi OX40L Antibody Hits Endpoints in Three Eczema Trials
Amlitelimab, a first-in-class monoclonal antibody that blocks OX40-ligand, met co-primary endpoints across three Phase 3 studies enrolling 1,833 patients with moderate-to-severe atopic dermatitis. The drug works through a mechanism distinct from every approved eczema biologic, and quarterly dosing matched monthly dosing in efficacy.
Key Takeaways
- Amlitelimab met co-primary endpoints in all three Phase 3 trials (COAST 1, COAST 2, SHORE) enrolling 1,833 patients across 14-16 countries
- EASI-75 response rates ranged from 35.9% to 48.1% on amlitelimab versus 19.1% to 32.3% on placebo at week 24
- Quarterly dosing (every 12 weeks) showed comparable efficacy to monthly dosing, a first among eczema biologics
- Amlitelimab is the first OX40L-blocking antibody to complete Phase 3 for atopic dermatitis, targeting T-cell activation upstream of IL-4, IL-13, and IL-31
Sanofi reported positive Phase 3 results for amlitelimab, a first-in-class monoclonal antibody targeting OX40-ligand, at the 2026 American Academy of Dermatology Annual Meeting in Denver on March 28. Three simultaneous trials enrolling 1,833 patients with moderate-to-severe atopic dermatitis all met their co-primary endpoints for skin clearance and itch reduction at 24 weeks.
The drug represents an entirely new approach to treating eczema. Where approved biologics like dupilumab block IL-4 and IL-13 downstream, and nemolizumab targets IL-31, amlitelimab works further upstream by blocking OX40-ligand on the surface of antigen-presenting cells. This prevents the costimulatory signal that activates and sustains pathogenic T cells in the first place.
How OX40L Targeting Differs from Current Eczema Biologics
Every biologic currently approved for moderate-to-severe atopic dermatitis targets a specific cytokine or receptor produced after T cells are already activated. Dupilumab blocks the IL-4 receptor alpha subunit. Tralokinumab neutralizes IL-13. Lebrikizumab also binds IL-13. Nemolizumab inhibits IL-31 receptor signaling. All of these sit at the effector stage of the immune cascade.
Amlitelimab operates one step earlier. OX40-ligand is expressed on antigen-presenting cells and binds to OX40 on activated T cells, delivering a costimulatory signal that promotes T-cell proliferation, survival, and cytokine production. By blocking this interaction, the drug dampens the inflammatory cascade before it generates the downstream cytokines that drive eczema symptoms. According to a 2024 review in the British Journal of Dermatology, OX40L/OX40 signaling contributes to the amplification and chronic persistence of T-cell-mediated inflammation in atopic dermatitis across Th2, Th1, Th17, and Th22 pathways.
The mechanism is also non-depleting. Amlitelimab blocks the OX40L-OX40 interaction without destroying T cells, which may explain the favorable safety profile observed across all three trials.
What Did the Three Phase 3 Trials Show?
The results across COAST 1, COAST 2, and SHORE were consistent. In COAST 1 (601 patients, 15 countries), 35.9% to 39.1% of patients on amlitelimab achieved EASI-75, a 75% or greater improvement in eczema severity, compared to 19.1% on placebo. In COAST 2 (589 patients, 16 countries), the EASI-75 rate was 40.5% to 41.8% versus 24.2%. SHORE (643 patients, 14 countries), which combined amlitelimab with topical corticosteroids, showed the strongest response: 46.8% to 48.1% versus 32.3%.
Skin clearance followed a similar pattern. Across all three studies, patients on amlitelimab were significantly more likely to achieve a validated Investigator Global Assessment score of 0 (clear) or 1 (almost clear) compared to placebo, according to Sanofi's press release on March 28, 2026.
Itch reduction was statistically significant across trials, though the magnitude varied. The percentage of patients achieving a 4-point or greater reduction on the peak pruritus numerical rating scale ranged from 22.5% to 38.2% on amlitelimab versus 12.7% to 21.5% on placebo.
Adverse event rates were comparable between drug and placebo arms. The most common side effects were nasopharyngitis and upper respiratory tract infections, both occurring at similar or lower rates than placebo in most trial arms. Two cases of Kaposi's sarcoma were reported across the entire 3,778-patient amlitelimab exposure pool, both in patients with known risk factors. No severe injection site reactions or gastrointestinal complications were observed.
Could Quarterly Dosing Change How Eczema Patients Manage Treatment?
The most striking finding may be the dosing interval. Amlitelimab dosed every 12 weeks performed comparably to every-4-week dosing across all three trials. In SHORE, the quarterly arm achieved an EASI-75 rate of 46.8%, nearly identical to the 48.1% seen with monthly dosing.
For context, dupilumab requires injection every two weeks. Tralokinumab and lebrikizumab are dosed every two to four weeks. A biologic that works with quarterly injections would represent a substantial reduction in treatment burden for the estimated 31 million Americans living with atopic dermatitis, many of whom also rely on barrier repair routines and protective topical ingredients to manage flares between treatments.
When Could Amlitelimab Reach Patients?
Sanofi has not yet filed for regulatory approval. Results from the ESTUARY Phase 3 extension study, evaluating long-term safety and maintenance dosing with the quarterly regimen, are expected in the second half of 2026. A regulatory submission would likely follow those results, placing a potential FDA decision in 2027 at the earliest.
The three completed studies enrolled patients aged 12 and older across North America, Europe, Asia, South America, and Africa, according to ClinicalTrials.gov registrations for COAST 1 (NCT06130566), COAST 2 (NCT06181435), and SHORE (NCT06224348).