Despite advancements over the years, cutaneous lupus erythematosus (CLE) continues to represent a high unmet medical need with no cure.
Patients with cutaneous lupus erythematosus (CLE) treated with litifilimab (BIIB059) had significantly superior reductions in skin disease over a 16-week period when compared with placebo, according to results published in The New England Journal of Medicine (NEJM).
“CLE can have a lasting negative impact on skin symptoms and emotional aspects of people’s lives, leading to a debilitating impact on quality of life and irreversible skin damage,” Victoria Werth, MS, MD, Professor of Dermatology at the University of Pennsylvania’s Perelman School of Medicine, stated. “Despite advancements over the past 2 decades, CLE represents a high unmet medical need with no cure. The LILAC study is among the first randomized controlled trials in CLE and I am encouraged by the publication of these positive results in NEJM.”
The randomized, double-blind, placebo-controlled phase 2 LILAC trail (NCT02847598) evaluated litifilimab, a humanized IgG1 monoclonal antibody (mAb) that targets blood dendritic cell antigen 2 (BDCA2) in patients with systemic lupus erythematosus (SLE; Part A) and CLE (Part B). BDCA2 has been reported to reduce inflammation from a subset of human immune cells known as plasmacytoid dendritic cells (pDCs), which are a major source of Type-I Interferon (IFN-I) and play an important role in the pathogenesis of lupus. Common symptoms of CLE include rash, itch, pain, and skin damage, such as dyspigmentation and irreversible scarring alopecia.
In Part B of the trial, patients with clinically confirmed CLE were randomly assigned to receive subcutaneous litifilimab (50, 150, or 450 mg) or placebo at weeks 0, 2, 4, 8, and 12. A dose-response model determine treatment response based on changes in the Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity score (CLASI-A) as well as safety. Eligible patients had active CLE, which was defined as a CLASI-A score of 8 or more, and either subacute CLE or chronic CLE.
Of the 132 patients enrolled in the study (litifilimab 50 mg: n = 26; litifilimab 150 mg: n = 25; litifilimab 450 mg: n = 48; placebo: n = 33), CLASI-A scores at baseline were 15.2, 18.4, 16.5, and 16.5, respectively. Baseline characteristics were similar among all participants. At week 16, scores decreased 24.3% in the 50 mg litifilimab group, 33.4% in the 150 mg group, and 28% in the 450 mg group. The drug was well tolerated by patients with CLE and most adverse events (AEs) were mild or moderate. The most frequent AEs, (reported in ≥5% patients receiving litifilimab) were upper respiratory tract infection, influenza, pruritus, cough, nasopharyngitis, headache, SLE, arthralgia, and injection-site erythema. Larger and longer studies are needed to determine the efficacy and safety of litifilimab in this patient population.
“Litifilimab was developed by Biogen scientists as a potential first-in-class therapy for lupus,” Nathalie Franchimont, MD, PhD, Head of the Multiple Sclerosis and Immunology Development Unit at Biogen, concluded. “These Phase 2 data underscore our goal of delivering meaningful new therapies to people with cutaneous lupus, an autoimmune disease affecting the skin that can occur with or without impacting other organs, who currently have limited treatment options. We are excited to progress this promising candidate into late-stage development to further evaluate its potential, particularly in those who historically have been underserved.”