Biogen's daxdilimab reduces disease activity in moderate-to-severe discoid lupus trial

In a phase 2 trial of 72 adults, the investigational antibody daxdilimab significantly reduced disease activity and skin symptoms in patients with moderate-to-severe discoid lupus erythematosus over 24 weeks. The drug, which targets and depletes plasmacytoid dendritic cells via ILT7 binding, demonstrated a favorable safety profile with no serious adverse events. This progress comes alongside clinical developments for Biogen's litifilimab, which downregulates rather than depletes these cells, highlighting new therapeutic pathways for a condition that currently lacks approved targeted treatments.

Efficacy of daxdilimab in phase 2 trial

• ▪At week 24 of the phase 2 daxdilimab trial, 60.3% of patients receiving low-dose daxdilimab and 51.6% receiving high-dose daxdilimab achieved a score of 0 or 1 on the Cutaneous Lupus Activity Investigator's Global Assessment, compared to 8.9% on placebo
• ▪In a phase 2 trial of 72 adults with moderate-to-severe discoid lupus erythematosus, treatment with daxdilimab resulted in a significant reduction in disease activity over 24 weeks

Safety of daxdilimab in phase 2 trial

• ▪One participant in the high-dose daxdilimab treatment group discontinued participation in a phase 2 trial for moderate-to-severe discoid lupus erythematosus as a result of arthralgia
• ▪No serious adverse events or deaths were reported in the phase 2 trial of daxdilimab for moderate-to-severe discoid lupus erythematosus, and treatment-related adverse events occurred in 58.3% of the low-dose, 56.5% of the high-dose, and 60% of the placebo cohorts

Mechanism of action of daxdilimab

• ▪Daxdilimab targets and depletes plasmacytoid dendritic cells, whereas litifilimab targets BDCA2 receptors on plasmacytoid dendritic cells to downregulate them without causing depletion
• ▪Daxdilimab is an investigational human immunoglobulin G subclass 1 monoclonal antibody that binds to immunoglobulin-like transcript 7, resulting in a targeted depletion of plasmacytoid dendritic cells associated with inflammation and skin lesions in cutaneous lupus erythematosus

Litifilimab mid-stage trial

• ▪In a mid-stage study of litifilimab, 27.2% of participants who received the drug from the beginning had clear or almost clear skin after one year, compared with 19% after 24 weeks
• ▪The mid-stage trial of litifilimab enrolled 93 adults whose skin symptoms had not responded to standard antimalarial medicines

Debatable claims

• ▪A 24-week trial is sufficient to establish the safety of cell-depleting therapies
• ▪Using placebo controls in trials for treatment-refractory discoid lupus is ethically acceptable