FDA Grants Breakthrough Therapy Designation to Litifilimab for Cutaneous Lupus Erythematosus

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to litifilimab (BIIB059), an investigational monoclonal antibody targeting blood dendritic cell antigen 2 (BDCA2), for the treatment of cutaneous lupus erythematosus (CLE).¹ The designation is based on phase 2 clinical data demonstrating improvement in skin disease activity and reflects regulatory recognition of CLE as a serious condition with limited therapeutic options.

Trial and Regulatory Overview

The breakthrough therapy designation for litifilimab was supported primarily by results from the phase 2 LILAC trial (NCT02847598), a randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of subcutaneous litifilimab in patients with CLE. The CLE cohort (LILAC Part B) enrolled adults with histologically confirmed CLE, with or without systemic lupus erythematosus, and assessed changes in skin disease activity over 16 weeks.

The primary endpoint was percent change from baseline in the Cutaneous Lupus Erythematosus Disease Area and Severity Index–Activity (CLASI-A) score. Across multiple dose groups, litifilimab treatment resulted in greater reductions in CLASI-A scores compared with placebo, with a dose-response relationship observed. Higher proportions of treated patients achieved clinically meaningful response thresholds (including CLASI-50 and CLASI-70), and investigator global assessments favored active treatment over placebo.² 

Safety findings in the phase 2 program were generally consistent with expectations for an immunomodulatory biologic. Most adverse events were mild to moderate in severity and included upper respiratory tract infections, headache, and injection-site reactions. Herpes infections were reported in some patients receiving higher doses, highlighting the importance of continued safety monitoring in larger and longer studies.² 

Litifilimab is currently being evaluated in the ongoing phase 3 AMETHYST program (NCT05531565), which is designed to further assess efficacy, safety, and durability of response in a broader CLE population. A data readout is anticipated in 2027.

Clinical Context and Unmet Need

CLE represents a spectrum of autoimmune skin diseases associated with chronic inflammation, photosensitivity, and the potential for irreversible scarring and dyspigmentation. Despite the significant impact on quality of life, no therapies are currently approved specifically for CLE, and management relies on off-label use of topical and systemic immunomodulatory agents. The FDA’s decision underscores both the unmet clinical need and the potential of targeted therapies aimed at pathogenic immune pathways.¹

CLE includes acute, subacute, and chronic subtypes that may occur independently or in association with systemic lupus erythematosus. Patients frequently experience relapsing disease marked by pain, pruritus, photosensitivity, and progressive skin damage that can result in scarring alopecia and permanent dyspigmentation.^3,4 These manifestations contribute to substantial psychosocial burden and reduced health-related quality of life.

Current management strategies emphasize photoprotection, topical corticosteroids, topical calcineurin inhibitors, and systemic antimalarial agents such as hydroxychloroquine. In refractory cases, systemic immunosuppressants or short courses of oral corticosteroids may be used, although supporting evidence is limited and long-term toxicity remains a concern.^5,6 The absence of approved, disease-specific therapies has been a longstanding challenge in dermatologic care of patients with CLE.

Drug and Mechanistic Background

Litifilimab is a humanized IgG1 monoclonal antibody that binds BDCA2, a receptor expressed selectively on plasmacytoid dendritic cells. Engagement of BDCA2 inhibits downstream signaling pathways involved in the production of type I interferons and other proinflammatory cytokines, which play a central role in lupus pathogenesis. By targeting this pathway, litifilimab represents a mechanistically novel approach for CLE.¹

Interpretation and Next Steps

The news is being met with enthusiasm from the field. "The breakthrough therapy designation for litifilimab illustrates the FDA’s recognition of cutaneous lupus as a serious disease that urgently requires new therapies," Victoria Werth, MD, MS, a professor of dermatology at the Perelman School of Medicine at the University of Pennsylvania, and a researcher on the phase 3 trial, said in a press statement. "With topical steroids and antimalarials as the initial therapies for managing CLE and no alternatives specifically approved for CLE, there is a need for effective, targeted treatments, and that could be a drug like litifilimab.”¹

“The FDA's designation reinforces Biogen’s belief that litifilimab could be a first-in-class therapy targeting BDCA2 for cutaneous lupus erythematosus,” added Priya Singhal, MD, MPH, executive vice president and head of development at Biogen. “This designation is a significant milestone for litifilimab as we advance the ongoing AMETHYST Phase 3 study, with the goal of bringing a new potential therapeutic option to the millions of people living with CLE.”¹

References

1. Biogen’s Litifilimab Receives FDA Breakthrough Therapy Designation for Cutaneous Lupus Erythematosus, a Disease With No Targeted Treatment Options. Press statement. Biogen. January 28, 2026. Accessed January 28, 2026. https://investors.biogen.com/news-releases/news-release-details/biogens-litifilimab-receives-fda-breakthrough-therapy

2. Werth VP, Furie R, Wallace DJ, et al. Trial of anti-BDCA2 antibody litifilimab for cutaneous lupus erythematosus. N Engl J Med. 2022;387(16):1528-1539.

3. Durosaro O, Davis MD, Reed KB, Rohlinger AL. Incidence of cutaneous lupus erythematosus, 1965-2005: a population-based study. Arch Dermatol. 2009;145(3):249-253.

4. Ogunsanya ME, Brown CM, Lin D, Imarhia F, Maxey C. Understanding the disease burden and unmet needs among patients with cutaneous lupus erythematosus. Int J Womens Dermatol. 2018;4(3):152-158.

5. Kuhn A, Landmann A, Bonsmann G. Cutaneous lupus erythematosus: update of therapeutic options part I. J Am Acad Dermatol. 2011;65(6):e179-e193.

6. Wallace DJ, Hahn BH, eds. Dubois’ Lupus Erythematosus and Related Syndromes. 9th ed. Elsevier; 2019.