Biogen Announces Positive Phase 2 Results for Litifilimab in Cutaneous Lupus Erythematosus at AAD 2026

Today at the American Academy of Dermatology (AAD) Annual Meeting, Biogen Inc. reported positive results from the phase 2 portion of the AMETHYST phase 2/3 trial evaluating litifilimab in patients with cutaneous lupus erythematosus (CLE).¹ This is the second successful phase 2 study of the investigational monoclonal antibody, reinforcing its potential as a first-in-class targeted therapy for a disease with no approved targeted treatments.

“I am encouraged by these results, which support the potential to bring litifilimab to patients with CLE, a condition where no targeted therapies are currently approved and where there are significant unmet needs,” said Joseph F. Merola, MD, Professor and Chair, Department of Dermatology and Professor of Internal Medicine in the Division of Rheumatic Diseases, UT Southwestern Medical Center. “These findings, alongside the FDA Breakthrough Therapy Designation, underscore the potential, if approved, of litifilimab for patients living with this challenging disease.”¹

AMETHYST is an ongoing, global, multicenter, randomized, double-blind, placebo-controlled trial designed to evaluate litifilimab in patients with active CLE across a range of disease severities. The study includes patients with subacute and chronic CLE who are refractory or intolerant to antimalarial therapy. Investigators enrolled a demographically representative population reflective of CLE epidemiology, including 74% women and 33% non-white participants. Participants were randomized to receive subcutaneous litifilimab or placebo every 4 weeks in addition to standard of care. The results reported reflect the 24-week, placebo-controlled phase 2 portion (Part A) of the trial.

Reported Results

The study met its primary endpoint, demonstrating a statistically significant improvement in skin disease activity at week 16. A greater proportion of patients receiving litifilimab achieved clear or almost clear skin, as defined by a Cutaneous Lupus Activity Investigators’ Global Assessment Revised (CLA-IGA-R) erythema score of 0–1, compared with placebo (14.7% vs 2.9%), corresponding to an 11.8% treatment difference (95% CI, 1.39–22.27; p < 0.05).

Secondary endpoints were also reached. Improvements were observed as early as week 4, with higher response rates in the litifilimab group based on CLASI-50 criteria compared with placebo (19.3% vs 5.5%). This separation was maintained through week 24, with 40.8% of treated patients achieving CLASI-50 compared with 21% in the placebo group. More stringent responses were also more frequent with active treatment, including CLASI-70 responses (21.7% vs 5.8%) and achievement of minimal disease activity (CLASI score 0–3) in 16.3% of litifilimab-treated patients versus none in the placebo arm.

Safety findings from AMETHYST were consistent with prior studies of litifilimab. Adverse events were reported in 74.6% of patients receiving the drug and 64.7% of those receiving placebo, with most events classified as mild to moderate. Serious adverse events occurred in 6.8% and 2.9% of patients in the litifilimab and placebo groups, respectively. No new safety signals were identified, supporting the overall tolerability profile observed in earlier research.

Regulatory Steps

Litifilimab is a humanized IgG1 monoclonal antibody directed against blood dendritic cell antigen 2 (BDCA2), a receptor expressed on plasmacytoid dendritic cells. Targeting BDCA2 reduces production of type I interferons and other pro-inflammatory mediators implicated in lupus pathogenesis. The drug has previously demonstrated efficacy in the phase 2 LILAC study, and together with the AMETHYST findings, has supported last month’s granting of Breakthrough Therapy Designation by the US Food and Drug Administration.² If confirmed in Phase 3, litifilimab could become the first targeted therapy approved for CLE in approximately 70 years. The phase 3 portion of AMETHYST is ongoing, with results currently blinded.

“The AMETHYST phase 2 results provide additional evidence of litifilimab’s potential in patients with CLE. It's a meaningful outcome to significantly reduce disease activity, given that ongoing active disease can lead to permanent scarring and disfigurement, and people living with CLE often face challenging physical, emotional, and social impacts on their daily lives. We are proud of the science behind this ‘Biogen developed’ molecule and our work to advance the understanding of this historically challenging and overlooked disease. We look forward to seeing results from the ongoing phase 3 part of the study, which will further evaluate litifilimab in patients with CLE,” Daniel Quirk, MD, Chief Medical Officer at Biogen, told Dermatology Times.

References

1. Biogen Announces Second Positive Phase 2 Litifilimab Trial in Cutaneous Lupus Erythematosus at 2026 American Academy of Dermatology Annual Meeting, Showing a Significant Reduction in Skin Disease Activity. News release. Biogen. Published March 28, 2026. Accessed March 28, 2026.

2. Werth VP, Furie RA, Romero-Diaz J, et al. Trial of anti-BDCA2 antibody litifilimab for cutaneous lupus erythematosus. N Engl J Med. 2022;387(4):321-331. doi:10.1056/NEJMoa2118024