Biogen reported that litifilimab met the primary endpoint in the Phase II portion of the AMETHYST Phase II/III trial in cutaneous lupus erythematosus, a setting with no approved targeted therapies, as per the firm's press release. Litifilimab met the primary endpoint in the Phase II portion of the AMETHYST Phase II/III trial in cutaneous lupus erythematosus, with the results presented at the 2026 American Academy of Dermatology Annual Meeting. The company said litifilimab, a monoclonal antibody targeting BDCA2, demonstrated a statistically higher rate of clear or almost clear skin compared to placebo at week 16 in patients with active CLE who were refractory or intolerant to antimalarial therapy.
In Part A of AMETHYST, 14.7% of litifilimab-treated participants achieved a CLA-IGA-R erythema score of 0–1 at week 16 versus 2.9% on placebo, an 11.8 percentage point difference (95% CI: 1.39, 22.27; p < 0.05). On the CLASI-50 measure, 40.8% of litifilimab participants achieved a 50% reduction in disease activity at week 24 compared to 21% on placebo (Δ = 19.8; CI: 1.46, 38.15), with separation from placebo observed as early as week 4. A CLASI-70 response was reported in 21.7% versus 5.8%, and 16.3% of litifilimab participants reached a CLASI score of 0–3 at week 24 compared to 0% on placebo. The company noted that secondary endpoints were not adjusted for multiplicity and therefore statistical significance cannot be demonstrated for those measures. Adverse events occurred in 74.6% (44/59) of litifilimab participants and 64.7% (22/34) of placebo participants over 24 weeks; serious adverse events were reported in 6.8% and 2.9%, respectively. Most adverse events were mild to moderate.
The AMETHYST trial is a two-part, multicenter, double-blind, placebo-controlled, randomized study enrolling participants with active subacute or chronic CLE. Part A enrolled 93 participants (59 litifilimab, 34 placebo); 74% were women and 33% were non-white. Participants received subcutaneous litifilimab or placebo every four weeks for 20 weeks, with an additional dose at Week 2, on top of standard of care. The Phase III portion remains ongoing and blinded. The absolute response rates on the primary endpoint were low in both arms, and the confidence intervals on secondary endpoints were wide, consistent with a small sample size. The data are from the Phase II portion and are based on the enrolled Part A population only.
Litifilimab is a humanized IgG1 monoclonal antibody that binds BDCA2 on plasmacytoid dendritic cells, reducing production of type I interferon and other pro-inflammatory mediators. Hydroxychloroquine, the current first-line therapy for CLE, achieves clinical response in up to 75% of patients in observational data, though no large randomized CLE-specific trials exist. Cross-trial comparisons are limited by differences in study design, duration, and patient populations.
Spot something wrong? Report an issue with this article