Litifilimab reduced the symptoms of lupus in a phase 2 study | AAD 2026

A first-in-class monoclonal antibody has shown significant reductions in skin disease in patients with cutaneous lupus erythematosus (CLE). Litifilimab met the primary endpoint of reduction of disease activity in people living with CLE at week 24, with more litifilimab patients achieving clear or almost clear skin, according to results from the AMETHYST trial presented today at the American Academy of Dermatology (AAD) Annual Meeting in Denver. This is the first time these data are being reported.

“In the last 80 years, there’s been no new approved treatment for cutaneous lupus,” lead investigator Victoria P. Werth, M.D., professor of Dermatology at the Hospital of the University of Pennsylvania, said in an interview. “We might have a treatment that works much more rapidly than any of the currently available therapies and hopefully mitigate the amount of [skin] damage.”

Cutaneous lupus erythematosus is an autoimmune skin disease that affects more women than men. It often appears between the ages of 20 and 50 years of age. Patients with the condition experience rash, pain, itch and photosensitivity as well as skin damage that worsens over time. The disease can lead to permanent scarring. The overall incidence rate of cutaneous lupus erythematosus was 3.9 per 100,000 people, according to a retrospective population-based cohort study that assessed medical records of people in one county in Minnesota between 1976 and 2018.

Topical steroids and antimalarials are the initial therapies to treat cutaneous lupus, and there is a need for effective targeted treatments.

Developed by Biogen, litifilimab is a monoclonal antibody that targets BDCA2, a receptor that is expressed on a subset of human immune cells called plasmacytoid dendritic cells. These immune cells produce type-I interferons. Binding to BDCA2 reduces production of pDCs, including type-I interferon, as well as other cytokines and chemokines, which are thought to play a major role in both systemic and cutaneous lupus.

AMETHYST is an ongoing, two-part phase 2/3 study to evaluate the efficacy and safety of litifilimab compared to placebo. The study will enroll a total of 450 patients across both parts. Of the 93 patients enrolled in part A, 59 received litifilimab along with standard of care and 34 patients received placebo plus standard of care every four weeks for 24 weeks. There was an extended treatment period where everyone received litifilimab for 28 weeks. The current standard of care for CLE includes topical steroids, antimalarials and immunosuppressants.

In part A, 74% of patients were women and 33% were non-white. This demographic is consistent with the epidemiology of cutaneous lupus erythematosus, which disproportionately affects women and diverse ethno-racial groups. Patients had moderate-to-severe disease.

Part A met its primary endpoint, demonstrating a statistically significant 11.8% higher reduction in disease activity in people living with cutaneous lupus erythematosus as measured by the Cutaneous Lupus Activity Investigators’ Global Assessment Revised (CLA-IGA-R) erythema score of 0-1 (clear/almost clear) at week 16 compared with placebo (14.7% vs. 2.9%). CLA-IGA-R is a clinician assessment of erythema (skin redness), hair follicle involvement, and other characteristics.

“There was a large difference between the placebo arm and the treatment arm, with the placebo arm actually being quite low in terms of not showing any improvement relative to the treatment arm,” Werth said.

Litifilimab also was associated with rapid and continued improvement in skin disease activity as early as week 4, as measured by the Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity 50 (CLASI-50), a secondary endpoint. Patients receiving litifilimab achieved a response compared with placebo as measured by CLASI-70 at week 24. CLASI is a tool used to measure improvements in disease severity and response to therapy for patients with lupus, with CLASI-50 assessing a reduction of disease activity of at least 50% and CLASI-70 assessing a reduction of at least 70%.

Litifilimab was generally well tolerated in the study. In the 24-week period, adverse events were reported in 74.6% of patients who received litifilimab and 64.7% of patients in the placebo arm. Most adverse events were mild to moderate in severity. Serious adverse events occurred in 6.8% in the litifilimab arm and 2.9% in the placebo arm.

In the ongoing phase 3 part of the study, patients will be assessed for 52 weeks. Patients will be randomized to receive litifilimab or placebo every four weeks for 20 weeks with an additional dose at week 2. All patients will then receive litifilimab during the 28-week extension. The Phase 3 data from the AMETHYST study of litifilimab in patients with lupus is expected to read out in 2027. A spokesperson for Biogen said the timing of the FDA submission is not yet available.

The FDA granted litifilimab breakthrough therapy designation in January 2026 based on the results of the phase 2 LILAC study, which was published in The New England Journal of Medicine in July 2022. This study enrolled 132 patients and assessed three different doses of litifilimab. Of those who received litifilimab, 26 received the 50-mg dose; 25 received the 150-mg dose and 48 received the 450-mg dose. The trial demonstrated that litifilimab reduced skin disease activity in people with CLE compared with placebo.