Treatment with daxdilimab resulted in a significant drop in disease activity and had a favorable safety profile in patients with moderate-to-severe discoid lupus erythematosus (DLE) over 24 weeks, according to new findings from a phase 2 trial.

The data were presented September 30 in a late breaker session at the European Academy of Dermatology and Venereology (EADV) 2026 Congress in Vienna. 

Daxdilimab is an investigational human immunoglobulin G subclass 1 (IgG1) monoclonal antibody that targets and binds to immunoglobulin-like transcript 7 (ILT7). ILT7 is a cell surface molecule specific to plasmacytoid dendritic cells (pDCs), which are associated with inflammation and skin lesions in DLE and other forms of cutaneous lupus erythematosus (CLE), according to investigators. The binding of daxdilimab to ILT7 results in a targeted depletion of pDCs.

"Approaches that target plasmacytoid dendritic cells seem to work in cutaneous lupus erythematosus, and the safety outcomes have been excellent," study first author Victoria Werth, MD, professor of dermatology and rheumatology at the University of Pennsylvania, Philadelphia, told Medscape Medical News.

Werth presented the study results at the meeting. 

The multicenter, randomized, double-blind, placebo-controlled, parallel-group study enrolled 72 patients aged 18-75 years with moderate-to-severe, treatment-refractory DLE for ≥ 6 months with active disease — defined as a Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity (CLASI-A) score of ≥ 8, without systemic features at baseline.

Patients were randomized to receive low-dose daxdilimab (n= 24), high-dose daxdilimab (n = 23), or placebo (n = 25) for 24 weeks, administered every 4 weeks from day 1 through week 20. Treatment response was evident after 4 weeks, Werth reported. At week 24, the mean change from baseline in CLASI-A (the primary endpoint) vs placebo was -6.0 (90% CI, -8.7 to -3.2; P = .0005) for low-dose daxdilimab and -5.7 (90% C,: -8.5 to -2.9; P = .0012) for high-dose daxdilimab. 

At 24 weeks, compared to 23.7% of those in the placebo group, 61.7% in the low dose group (P = .0037) and 62.1% in the high dose group (P = .0044) achieved at least a 50% reduction in the CLASI-A score, a secondary endpoint.

Another secondary endpoint was the proportion of patients who achieved a score of 0 or 1 on the Cutaneous Lupus Activity Investigator's Global Assessment at week 24: 60.3% of those on the low dose (P < .0001) and 51.6% of those on the high dose (P = .0007) met this endpoint, vs 8.9% of those on placebo.

No serious adverse events or deaths were reported. Treatment-related adverse events occurred in 58.3%, 56.5%, and 60% of patients in the low-dose, high-dose, and placebo cohorts, respectively. One participant in the high-dose group discontinued as a result of arthralgia.

Daxdilimab, Werth told Medscape, works differently than other treatments that target pDCs. In particular, she compared the drug to litifilimab, another investigational humanized IgG1 monoclonal antibody that is being studied for CLE, which received a breakthrough therapy designation earlier this year from the FDA. 

"Daxdilimab is targeted to plasmacytoid dendritic cells and depletes them," she explained. "Litifilimab targets dendritic cells and downregulates them without depleting them. Some other approaches block all the type I interferons by blocking the receptor, which is a different mechanism. Other approaches have direct blocking effects on toll receptors that generate type I [interferons] by blocking several relevant cell types."

In August, Amgen announced it was "taking steps to advance daxdilimab to a registrational phase of development" but has offered no additional details. 

Werth disclosed financial relationships with multiple companies, including Amgen, the manufacturer of daxdilimab. 

Scott Harris has been covering dermatology for more than a decade. He lives near Washington, DC.