Litifilimab Lessens Skin Disease Activity in Lupus, Trial Data Show
Therapy known as BIIB059 led to 'huge improvements,' researchers say
Biogen’s experimental therapy litifilimab, also called BIIB059, significantly reduced skin disease activity in adults with cutaneous lupus erythematosus (CLE), according to data from part B of the Phase 2 LILAC trial.
CLE is a type of lupus that’s also known as skin lupus. As its name suggests, skin lupus is a type of this autoimmune inflammatory disease that affects the skin — but this specific form also can impact internal organs, such as the joints, kidneys, and lungs.
These early findings mean that LILAC (NCT02847598) — one of the first appropriately controlled CLE trials, according to litifilimab developer Biogen — met its main goal of showing that BIIB059 was superior to a placebo at lessening skin disease activity after four months.
“Some patients in our trial saw huge improvements within a month,” Victoria Werth, MD, one of the trial’s investigators and a professor of dermatology at the University of Pennsylvania Perelman School of Medicine, said in a university press release.
New treatments for ‘skin lupus’
These results “underscore our goal of delivering meaningful new therapies to people with cutaneous lupus … who currently have limited treatment options,” Nathalie Franchimont, MD, PhD, head of Biogen’s multiple sclerosis and immunology development unit, said in a separate company press release.
Werth noted that immunosuppressants, often currently administered in cases of severe disease, “have a lot of side effects like higher risk of infection.”
“Not only do the available drugs not always work, but they are also not always well tolerated,” she said.
As such, treatments with different mechanisms of action, such as litifilimab — discovered and developed in-house as BIIB059 by Biogen scientists — “could be pivotal,” added Werth, who also is the chief of dermatology at the Corporal Michael J. Crescenz Veterans Affairs Medical Center, in Philadelphia.
The trial’s results were detailed in a new study, “Trial of Anti-BDCA2 Antibody Litifilimab for Cutaneous Lupus Erythematosus,” published in the New England Journal of Medicine.
Biogen plans to initiate a pivotal trial in CLE later this year — the findings of which, if positive, may support future regulatory submissions seeking the therapy’s approval for this indication.
The company also is testing litifilimab against a placebo in clinical trials for adults with systemic lupus erythematosus (SLE) — the most common lupus form, which typically also affects other organs and systems.
The Phase 3 TOPAZ-1 trial (NCT04895241), expected to enroll 540 participants, is recruiting patients at 71 sites worldwide.
Meanwhile, TOPAZ-2 (NCT04961567), another Phase 3 trial testing BIIB059, is also enrolling an estimated 540 patients, also at study centers across the globe.
The primary objective of both studies “is to demonstrate efficacy of BIIB059 compared with placebo in participants with active systemic lupus erythematosus (SLE), who are receiving background lupus standard of care (SOC) therapy in reducing disease activity.”
Like other autoimmune diseases, lupus is characterized by the production of antibodies that wrongly recognize certain proteins in the body as foreign, mounting immune attacks against them. CLE is a form of lupus that affects the skin and can occur in the presence or absence of SLE.
“CLE can cause scarring, atrophy in the skin, and skin discoloration, as well as permanent hair loss,” Werth said. “These impacts on physical appearance also affect mental and emotional health and well-being.”
No new CLE-specific therapies have been approved for more than 50 years. Moreover, the few that are available are used off-label — meaning they were designed for a different disease or condition — or were grandfathered into use.
Litifilimab is an antibody designed to reduce the production of pro-inflammatory molecules such as type 1 interferons (IFN-I). These molecules are produced by plasmacytoid dendritic cells, a type of immune cell implicated in lupus.
It works by binding to BDCA2, a receptor protein exclusively found at the surface of these cells, which can travel throughout the body, promoting inflammation and lesion formation.
Litifilimab in clinical trials
Data from a previous Phase 1 trial (NCT02106897) showed the therapy safely and effectively reduced IFN-I levels, inflammation, and skin lesions in people with SLE.
The global, two-part Phase 2 LILAC trial tested litifilimab (at the start still known as BIIB059) against a placebo in 264 adults, ages 18–75. The participants were split into groups of 132 for each of its two parts. Part A included SLE patients with active skin manifestations and joint involvement, while part B included people with moderate-to-severe active CLE, with or without SLE.
The newly published results concern LILAC’s part B. Detailed findings from part A, which also met its main goal of reducing disease activity in the joints, will be published separately.
In part B, participants were randomly assigned to receive under-the-skin (subcutaneous) injections of either one of three doses of litifilimab — 50, 150, or 450 mg — or a placebo, for 12 weeks, or about three months. A total of five doses were given at weeks 0, 2, 4, 8, and 12.
“Participants’ demographic characteristics were broadly representative of the wider population with cutaneous lupus erythematosus,” the researchers wrote, adding that about 10% of those who reported race/ethnicity identified as Black or African American.
About 42–48% of patients in the litifilimab groups, as well as 42% of those on the placebo, also had SLE, and about 90% were receiving background therapy. Most patients in each group completed the placebo-controlled treatment period.
Results at week 16 showed the therapy led to a significant dose-dependent reduction in skin disease activity relative to a placebo, as measured by the Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) score.
This measure involves the analysis and scoring of 13 skin regions based on signs of disease activity, with higher scores indicating more widespread or severe disease.
Specifically, the CLASI-A score dropped by 24.3% in the 50 mg litifilimab group, and by 28% among those receiving the 450 mg dose, when compared with the placebo group. The largest reduction was seen in the 150 mg group, for whom the CLASI-A score dropped by 33.4% relative to those on the placebo.
Most secondary goals, mainly consisting of changes in other CLASI-A-based measures, were not met. Exceptions included a reduction of at least 50% in CLASI-A scores at 12 and 16 weeks for the 450 mg litifilimab dose only, and four-point or greater drops at weeks 12 and 16 for the 150 mg litifilimab dose only.
The therapy was generally safe and well-tolerated, with most adverse events being mild to moderate in severity. The most common adverse events included common cold, headache, injection-site redness, SLE, joint pain, upper respiratory tract infection, influenza, itchy skin, and cough.
The rates of adverse events and serious adverse events were slightly higher with litifilimab. Three cases of abnormal immune reactions, including one serious event, were reported in the litifilimab groups, resulting in treatment withdrawal.
Overall, these findings support litifilimab as a potential therapy for CLE.
“Larger and longer trials are needed to determine the effect and safety of litifilimab for the treatment of cutaneous lupus erythematosus,” the researchers wrote.
Biogen, in collaboration with UCB, is also testing another SLE candidate, dapirolizumab pegol, in a Phase 3 clinical trial (NCT04294667). Enrollment is ongoing, with patients being recruited at 230 sites worldwide.
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