Daxdilimab Improves Disease Activity in Treatment-Refractory Discoid Lupus in Phase 2 Trial

Late-breaking phase 2 data presented at the 2026 European Academy of Dermatology and Venereology (EADV) Congress demonstrated significant improvements in disease activity with daxdilimab in patients with moderate to severe, treatment-refractory discoid lupus erythematosus (DLE).

The randomized, placebo-controlled trial (NCT05591222) evaluated 2 doses of investigational daxdilimab, a human IgG1 monoclonal antibody targeting immunoglobulin-like transcript 7 (ILT7), in patients with chronic DLE. Both doses met the study's primary and secondary efficacy endpoints at week 24.

Targeting pDCs in Discoid Lupus

DLE is the most prevalent form of chronic cutaneous lupus erythematosus and is characterized by erythematous, scaly lesions that commonly occur on the scalp, face, and ears. Disease progression can result in permanent scarring, alopecia, and facial disfigurement, contributing to a substantial impact on patients' quality of life.

Plasmacytoid dendritic cells (pDCs) are increased in lesional skin in patients with cutaneous lupus erythematosus and are implicated in disease pathogenesis through their association with type I interferon biology. Daxdilimab targets ILT7, a cell-surface protein exclusively expressed on pDCs. Binding to ILT7 is designed to reduce pDCs in the tissue and blood.

Phase 2 Trial Evaluates 2 Daxdilimab Doses

The multicenter, randomized, double-blind, placebo-controlled trial enrolled adults aged 18 to 75 years with chronic, moderate-to-severe, treatment-refractory DLE for at least 6 months. Patients were required to have active disease at baseline, defined as a Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity (CLASI-A) score of at least 8, without systemic features.

A total of 72 patients were randomized 1:1:1 to low-dose daxdilimab (n = 24), high-dose daxdilimab (n = 23), or placebo (n = 25). Treatment was administered every 4 weeks from day 1 through week 20, with efficacy and safety assessed through week 24. The primary endpoint was mean change from baseline in CLASI-A at week 24.

Secondary endpoints included the proportion of patients achieving at least a 50% reduction in CLASI-A, or CLASI-50, and the proportion achieving a score of 0 or 1 on the Cutaneous Lupus Activity Investigator's Global Assessment (CLA-IGA).

The mean patient age was 48.8 years, and 69.4% of participants were female. Mean baseline CLASI-A and CLA-IGA scores were 15.2 and 3.1, respectively.

Daxdilimab Meets Primary and Secondary Endpoints

Both daxdilimab doses produced significant reductions in CLASI-A compared with placebo at week 24, with treatment responses observed as early as week 4.

At week 24, the least-squares mean difference in change from baseline in CLASI-A versus placebo was –6.0 with low-dose daxdilimab (90% CI, –8.7 to –3.2; P = .0005) and –5.7 with high-dose daxdilimab (90% CI, –8.5 to –2.9; P = .0012).

Clinically meaningful responses were also observed across the secondary endpoints. CLASI-50 response rates at week 24 were:

• 61.7% with low-dose daxdilimab vs 23.7% with placebo (P = .0037)
• 62.1% with high-dose daxdilimab vs 23.7% with placebo (P = .0044)

CLA-IGA 0/1 responses were achieved by 60.3% of patients receiving low-dose daxdilimab and 51.6% receiving high-dose daxdilimab, compared with 8.9% receiving placebo (P < .0001 and P = .0007, respectively).

The efficacy curves included with the abstract also show separation between both daxdilimab groups and placebo over the 24-week treatment period across CLASI-A, CLASI-50, and CLA-IGA 0/1 outcomes.

Safety Findings

Daxdilimab was generally well tolerated through week 24, with no serious adverse events or deaths reported.

Treatment-related adverse events occurred in 58.3% of patients in the low-dose group, 56.5% in the high-dose group, and 60.0% in the placebo group. One patient receiving high-dose daxdilimab discontinued the study because of arthralgia.

Investigators concluded that the improvements across the primary and secondary endpoints, together with the observed safety profile, support further investigation of pDC targeting in DLE. The findings also provide additional evidence for the role of pDCs in DLE pathogenesis and the potential of targeting this pathway in patients with moderate-to-severe disease.

References

1. Werth V, Merola JF, Chong B, et al. Daxdilimab in moderate-to-severe discoid lupus erythematosus: efficacy and safety results from a phase 2, randomised, placebo-controlled trial. Late-breaking abstract LB-136. Presented at: European Academy of Dermatology and Venereology Congress; 2026.
2. Drenkard C, Parker S, Aspey LD, et al. Racial disparities in the incidence of primary chronic cutaneous lupus erythematosus in the southeastern US: the Georgia Lupus Registry. Arthritis Care Res (Hoboken). 2019;71(1):95-103.
3. Karnell JL, Wu Y, Mittereder N, et al. Depleting plasmacytoid dendritic cells reduces local type I interferon responses and disease activity in patients with cutaneous lupus. Sci Transl Med. 2021;13(595):eabf8442.