Litifilimab Shown to Reduce Number of Swollen Joints in Phase 2 Trial
Lupus treatment candidate meets main goal in LILAC
Litifilimab (BIIB059), Biogen’s investigational antibody-based treatment for systemic lupus erythematosus (SLE), significantly reduced the number of swollen and tender joints in people with the autoimmune inflammatory disease over six months, new trial data show.
With these positive results, the treatment candidate met the main goal of part A of the Phase 2 LILAC trial.
“At Biogen, our goal is to discover and develop new treatment options that not only reduce lupus disease activity but also decrease clinical manifestations that impact patients the most,” Nathalie Franchimont, MD, PhD, head of Biogen’s multiple sclerosis and immunology development unit, said in a press release.
LILAC (NCT02847598), enrolling 264 participants overall, was comprised of two parts. Part A evaluated the treatment in SLE patients, while part B investigated it in people with cutaneous lupus erythematosus (CLE), a type of lupus that affects the skin.
Totality of data
Data from part B, published earlier this summer, showed the treatment also reduced skin disease activity in CLE patients, meeting the main goal for that portion of the trial.
Results from part A of LILAC have now been published in the New England Journal of Medicine (NEJM), in a study titled “Trial of Anti-BDCA2 Antibody Litifilimab for Systemic Lupus Erythematosus.”
“This second NEJM manuscript shows the totality of data from the Phase 2 LILAC program, reinforcing our belief in the potential of litifilimab as a first-in-class therapy for both systemic and cutaneous lupus,” Franchimont said.
Two concurrent Phase 3 clinical trials — TOPAZ-1 (NCT04895241) and TOPAZ-2 (NCT04961567) — are evaluating the efficacy and safety of about a year of treatment with litifilimab against a placebo in SLE patients with active disease. The participants also are receiving background lupus standard of care therapy. TOPAZ-1 and TOPAZ-2 are each enrolling up to 540 participants at multiple sites worldwide.
As part of Biogen’s commitment to diversity in clinical trials, the TOPAZ studies will have enrollment targets to achieve adequate representation of African American and Hispanic/Latino communities. The company also plans to launch a pivotal study of the experimental treatment in CLE patients this year.
“We look forward to continuing our evaluation of litifilimab in Phase 3 studies and sharing additional data when available,” Franchimont said.
Litifilimab is an antibody designed to bind to BDCA2, a protein found on the surface of plasmacytoid dendritic cells — a type of immune cell implicated in lupus. In doing so, litifilimab is expected to lower the cells’ production of inflammatory molecules, like type one interferons (IFN-1), that drive inflammation in lupus.
A previous Phase 1 trial (NCT02106897) demonstrated that the treatment safely and effectively lowered IFN-1 levels, inflammation, and skin lesions in SLE patients.
“Litifilimab has been shown to inhibit the production of type I interferons as well as other inflammatory mediators produced by plasmacytoid dendritic cells. Strong evidence has accumulated that these mediators contribute to disease activity in lupus,” said Richard Furie, MD. Furie is the Marilyn and Barry Rubenstein Chair in rheumatology, chief of the division of rheumatology at Northwell Health, and professor at the Feinstein Institutes for Medical Research.
Part A of LILAC involved 132 SLE patients with active skin manifestations and joint involvement, while part B included 132 people with moderate to severe active CLE, either with or without SLE.
The new publication concerned part A, in which participants were randomly assigned to receive subcutaneous (under-the-skin) litifilimab — at a dose of 50, 150, or 450 mg — or a placebo. The therapy was administered over the course of about five months, at weeks 0 (the study’s start), 2, 4, 8, 12, 16, and 20.
Most participants were female, making up 98% of patients in the litifilimab group and 88% of those in the placebo group. About 10% of participants were Black or African American, although race and ethnicity were not reported for 35 participants enrolled at sites in Europe.
Assessing litifilimab for swollen joints
Due to protocol changes during the trial, only those receiving the 450 dose or a placebo who had at least four swollen joints and four tender joints at the study’s start were included in the trial’s primary efficacy analysis. This included 56 litifilimab-treated patients and 46 participants who were given a placebo.
The main goal was to evaluate the change from the study’s start in the total number of active joints — defined as the sum of swollen joints and tender joints — after 24 weeks, or about six months.
The mean number of active joints at the study’s start was 19 in the litifilimab group and 21.6 in the placebo group. Those in the litifilimab group experienced a significantly greater reduction in the number of active joints after six months compared with the placebo group. Specifically, treated patients experienced a mean reduction of 15 active joints compared with 11.6 in the placebo group.
Most secondary endpoints were not met, but evidence that litifilimab could reduce cutaneous (skin) manifestations and global disease activity were observed. However, “as a phase 2 trial, it was not powered to assess the secondary end points, and no conclusions can be drawn from these results,” the researchers wrote.
Safety was evaluated in all 132 enrolled participants. Litifilimab was generally well-tolerated, with adverse events reported in 59% of litifilimab-treated patients compared with 68% of those given a placebo.
Most reported side effects were mild to moderate in severity. The most commonly reported adverse events in the litifilimab group were diarrhea, cold-like symptoms, urinary tract infection, falls, and headache.
Serious adverse events were reported in four participants who received the investigational treatment and six who received a placebo. No significant abnormal lab or heart tests were reported with litifilimab’s use.
The findings overall support the use of litifilimab as an SLE therapy, but “larger and longer trials are necessary to determine the effect and safety of litifilimab in patients with SLE,” the team concluded.