Sanofi announced positive results from a Phase 2a study evaluating the safety and efficacy of amlitelimab, a human monoclonal antibody targeting key immune system regulator OX40-Ligand, were presented as a late-breaker on September 30, 2021 at the European Academy of Dermatology and Venerology (EADV) 2021 Virtual Congress. In the study, amlitelimab showed significant improvements in signs and symptoms of moderate-to-severe atopic dermatitis with a well-tolerated safety profile in adults whose disease cannot be adequately controlled with topical medications or for whom topical medications are not a recommended treatment approach. In this Phase 2a double-blind, placebo-controlled study, participants were randomized to either intravenous amlitelimab-low dose (LD) (n=29), intravenous amlitelimab-high dose (HD) (n=30) or placebo (n=29) and were treated every four weeks over a 12-week period. Eligible patients included adults with moderate-to-severe atopic dermatitis whose disease is inadequately controlled with topical therapies such as corticosteroids, or where such therapies were not advisable. Co-primary endpoints included percent change in EASI from baseline, and incidence of treatment-emergent adverse events (TEAEs), at week 16. At week 16, the data demonstrated that when dosed every four weeks: Patients treated with amlitelimab-LD showed 80% improvement in average EASI from baseline, and patients treated with amlitelimab-HD showed 70% improvement in average EASI from baseline, compared to 49% for the placebo group (p=0.009 and p=0.072, respectively). The difference between amlitelimab-LD and placebo was nominally statistically significant. The onset of response versus placebo was seen as early as Week 2 for both amlitelimab groups. No meaningful difference in responses was seen for the amlitelimab-LD and amlitelimab-HD groups. The overall rate of TEAEs was 35% for amlitelimab-LD, 17% for amlitelimab-HD and 31% for placebo. One serious adverse event was reported in the amlitelimab-LD group (infected atheroma) deemed related by the investigator at week 16; the event was resolved, and the patient was able to complete the study. No hypersensitivity reactions were reported. Also, at 16 weeks, key secondary endpoint data included: 44% of patients treated with amlitelimab-LD and 37% of patients treated with amlitelimab-HD achieved a score of 0 (clear) or 1 (almost clear) on the validated Investigator's Global Assessment (vIGA) scale compared with 8% with placebo (p<0.001 both LD and HD). The vIGA is a 5-point scale ranging from 0 (clear) to 4 (severe) that measures the overall severity of skin lesions. 59% of amlitelimab-LD and 52% of amlitelimab-HD patients achieved 75% or greater skin improvement (EASI-75) compared to 25% with placebo. 33% of amlitelimab-LD and 30% of amlitelimab-HD patients achieved 90% or greater skin improvement (EASI-790 compared to 13% with placebo. A 60% improvement in the amlitelimab-LD group and a 59% improvement in the amlitelimab-HD group compared with 37% improvement in the placebo group in mean percent change from baseline in SCORing Atopic Dermatitis (SCORAD), a combined measure of area and severity of atopic dermatitis on the skin as well as patient-reported symptoms of itch and sleeplessness, (p=0.011 and p=0.016, respectively). At Week 36, 68% of patients who achieved a vIGA score of 0 or 1 at Week 16 maintained their response — 24 weeks after their last dose. Amlitelimab is a fully human non-depleting monoclonal antibody that binds to OX40-Ligand, a key immune regulator, and has the potential to be a first-in-class treatment for a range of immune-mediated diseases and inflammatory disorders, including moderate-to-severe atopic dermatitis. By targeting OX40-Ligand, amlitelimab aims to restore immune homeostasis between pro-inflammatory and anti-inflammatory T cells. Amlitelimab is being studied in patients with moderate-to-severe atopic dermatitis with suboptimal response to topical therapies. The potential for long-lasting treatment responses in atopic dermatitis patients may help reduce the burden of frequent dosing, and further investigation will be conducted in a future Phase 2b study. Amlitelimab is currently under clinical investigation, and its safety and efficacy have not been evaluated by any regulatory authority.