52-Week Litifilimab Data in Cutaneous Lupus Erythematosus

Response rates with litifilimab, a monoclonal antibody targeting blood dendritic cell antigen 2 (BDCA2), continued to rise through week 52 in patients with cutaneous lupus erythematosus (CLE) refractory or intolerant to antimalarials, according to Victoria P. Werth, MD, professor of dermatology and medicine at the University of Pennsylvania, and François Chasset, MD, PhD, professor of dermatology at Sorbonne Université and Hôpital Tenon in Paris. The 2 discussed the phase 2 AMETHYST Part A data in an HCPLive special report from the European Academy of Dermatology and Venereology (EADV) Congress 2026 in Vienna, Austria (September 30–October 3). The findings come from a Biogen-sponsored congress abstract that has not been peer-reviewed, and both speakers are authors on it.¹

AMETHYST Part A (NCT05531565) randomized 93 adults to subcutaneous litifilimab (n = 59) or placebo (n = 34) every 4 weeks through week 24, after which all participants received litifilimab through week 52.¹ Chasset noted the cohort was 74% women and 33% non-white. At week 16, 14.7% of litifilimab participants achieved clear or almost clear skin on the Cutaneous Lupus Activity Investigators’ Global Assessment Revised (CLA-IGA-R) erythema score versus 2.9% with placebo (difference, 11.8%; 95% CI, 1.39–22.27).² “There’s been no approved therapies for over 80 years in cutaneous lupus, and we’re really on a cusp of changing the way that we practice,” Werth said.

Among participants who started litifilimab at baseline, response rates rose from week 24 to week 52 for CLA-IGA-R erythema 0–1 (19.0% to 27.2%), Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) 70 (21.7% to 28.8%), and CLASI-50 (40.8% to 46.0%), while CLASI–Activity 0–3 held at 16.3% to 16.7%.¹ Participants who switched from placebo at week 24 began responding within about 4 weeks, reaching week-52 rates of 33.7%, 35.4%, 48.5%, and 22.2%, respectively.¹ Werth cautioned that after week 24 the comparisons are largely within group rather than placebo-controlled, so the extension speaks to durability rather than relative efficacy. Adverse events in the extended period occurred in 76.8% and 78.1% of early and late starters, respectively, nearly all mild or moderate; serious adverse events occurred in 3.6% and 3.1%, and no serious viral infections were observed.¹

Chasset said litifilimab reduces type I interferon and other proinflammatory cytokines by binding BDCA2 on plasmacytoid dendritic cells. He also highlighted a companion analysis from AMETHYST Part A defining meaningful within-patient change in CLASI–Activity as a 7.0- to 8.0-point decrease or a 35% to 50% reduction, with percentage change tracking clinician and patient perceptions more closely and supporting CLASI-50 and CLASI-70 as trial endpoints.³ Chasset added that a separate EADV analysis of RNA sequencing data from the earlier LILAC trial showed interferon-pathway signatures declining over time, which he said could eventually help identify likely responders.

The phase 3 portion of AMETHYST remains blinded and ongoing, and litifilimab received FDA Breakthrough Therapy designation for CLE in January 2026.⁴ Chasset said a phase 3 readout in systemic lupus erythematosus is expected later in 2026.

Relevant disclosures for Chasset include AstraZeneca, Biogen, BMS, GSK, Celgene, Merck, Horizon Therapeutics, Novartis, Kyowa Kirin and Principabio. Relevant disclosures for Werth include Xoma, RPS, Janssen/Centocor, Biogen-Idec, Sanofi-Aventis, UVC, Novartis, Idera, Pfizer, Lupus Foundation of America, Medimmune, Rigel, Merck, Genentech, GSK Stiefel and Celgene.

References

1. Merola JF, Werth V, Chong B, et al. Efficacy and safety of litifilimab in cutaneous lupus erythematosus (CLE): 52-week results of the phase 2 study, AMETHYST Part A. Abstract 1846. Presented at: European Academy of Dermatology and Venereology (EADV) Congress 2026; September 30-October 3, 2026; Vienna, Austria.

2. Biogen. 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. March 28, 2026.

3. Chasset F, Werth V, Fernandez A, et al. Defining clinically meaningful change in Cutaneous Lupus Erythematosus Disease Area and Severity Index–Activity (CLASI-A) scores: data from AMETHYST Part A, a phase 2 study of litifilimab in cutaneous lupus erythematosus. Abstract 2364. Presented at: EADV Congress 2026; September 30-October 3, 2026; Vienna, Austria.

4. Biogen Inc. Quarterly report (Form 10-Q) for the period ended June 30, 2026. US Securities and Exchange Commission.