Positive phase II data on litifilimab (BIIB059) in cutaneous lupus erythematosus published in 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,” said Victoria Werth, M.S., M.D., Professor of Dermatology at the University of Pennsylvania’s Perelman School of Medicine. “Despite advancements over the past two 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.”

Biogen has progressed litifilimab to late-stage development and is actively enrolling participants with systemic lupus erythematosus into the Phase III TOPAZ-1 and TOPAZ-2 studies, with plans to initiate a pivotal study in CLE this year. Litifilimab has a novel mechanism of action that engages blood dendritic cell antigen 2 (BDCA2), a receptor solely expressed on the surface of plasmacytoid dendritic cells, resulting in decreased production of type 1 interferons, cytokines and chemokines at the site of inflammation such as the skin.

The Phase II LILAC Part B Results :LILAC was a randomized, double-blind, placebo-controlled study that evaluated the efficacy and safety of litifilimab versus placebo in two parts: Part A in participants who had systemic lupus erythematosus (SLE) with active joint and skin manifestations; and Part B in participants with moderate-to-severe active CLE, including active subacute and chronic subtypes, with or without systemic manifestations.

As previously reported, both Part A and Part B of the study met their respective primary endpoints, with litifilimab demonstrating superior efficacy to placebo in reducing total active joint count and improving skin disease activity in participants with SLE and CLE, respectively. Part B of the LILAC study assessed multiple doses of litifilimab or placebo in participants with active, histologically confirmed CLE. The primary analysis included a test of dose-response to assess whether there was a response across the four dose groups (placebo, 50, 150, or 450 mg litifilimab, administered subcutaneously at weeks 0, 2, 4, 8, and 12) on the basis of the primary endpoint of skin disease activity. This Phase II trial was not powered to assess secondary endpoints.

The LILAC study population in Part B was representative of the broader CLE patient population, with approximately 10 percent of participants who reported race and ethnicity identifying as Black or African American. In Part B, litifilimab demonstrated a significant dose-response relationship based on the percent change from baseline in the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI-A) score (primary endpoint), a measure of skin disease activity, at Week 16. In Part B, litifilimab was generally well tolerated, with most reported adverse events (AEs) rated as mild or moderate. The most common AEs reported in greater than 5% of participants in the pooled litifilimab groups were nasopharyngitis, headache, injection-site erythema, SLE, arthralgia, upper respiratory tract infection, influenza, pruritus, and cough.

Detailed findings for Part A of LILAC, which enrolled participants with SLE with active joint and skin manifestations, will be published separately in a peer-reviewed journal.

See-ORIGINAL ARTICLE.VOL. 387 NO. 4, JUL 28, 2022 "Trial of Anti-BDCA2 Antibody Litifilimab for Cutaneous Lupus Erythematosus"-V.P. Werth and Others.N Engl J Med 2022; 387:321-331.