Dazukibart effectively reduces disease activity in patients with dermatomyositis: Study

A new study published in The Lancet journal showed that dermatomyositis disease activity is reduced by Dazukibart which addresses certain chronic systemic autoimmune disease molecular pathologies.

Type I interferon (IFN) dysregulation is a hallmark of the pathogenesis of dermatomyositis, a chronic autoimmune disease that causes characteristic cutaneous eruptions and muscular weakening. To evaluate the effectiveness, safety, and target engagement of dazukibart (humanized, selective IgG1 neutralizing monoclonal antibody that targets IFNβ) in people with moderate-to-severe dermatomyositis, David Fiorentino and team undertook this study.

This multicenter phase 2 trial, conducted across 25 sites in 5 countries, enrolled patients with dermatomyositis. Stage 3 included those with muscle-predominant disease and moderate muscular involvement, while stages 1, 2, and 2a included adults (18–80) with skin-predominant disease, requiring prior therapy failure and a CDASI-A score ≥14.

The patients were randomly assigned to dazukibart or placebo with varying doses and sequences. In stage 1, they received dazukibart 600 mg or placebo; in stage 2, dazukibart 600 mg, 150 mg, or placebo. In stages 2a and 3, treatments alternated and were swapped at week 12. Treatment was blinded and delivered via IV every 4 weeks. 

The change from baseline in CDASI-A score at week 12 as evaluated in the complete analysis set and the pooled skin FAS was the main outcome for the skin-predominant cohorts, whereas safety was the main endpoint for the muscle-predominant cohort.

Nearly 50 persons were eliminated from the 125 adults who were evaluated between January 23, 2018, and February 23, 2022. 75 individuals received treatment after being allocated at random. The majority of patients were women.

The mean change from baseline in CDASI-A for dazukibart 600 mg in the FAS in stage 1 at week 12 was -18·8. The dazukibart 600 mg group's mean decrease from baseline in CDASI-A in the pooled skin FAS at week 12 was -19·2, whereas the dazukibart 150 mg group's was -16·6.

Infections and infestations were the most frequent treatment-emergent adverse events which occurred in 12 (80%) of 15 patients in the dazukibart 150 mg group, 30 (81%) of 37 in the dazukibart 600 mg group, and 18 (78%) of 23 in the placebo group. Significant side effects occurred in 4 individuals (11%) in the dazukibart 150 mg group and 1 (4%) in the placebo group.

One stage 3 patient who received dazukibart 600 mg followed by placebo died during follow-up due to hemophagocytic lymphohistiocytosis and macrophage activation syndrome. Overall, Dazukibart was well tolerated and significantly reduced disease activity by highlighting IFNβ inhibition as a promising treatment for dermatomyositis.

Source:

Fiorentino, D., Mangold, A. R., Werth, V. P., Christopher-Stine, L., Femia, A., Chu, M., Musiek, A. C. M., Sluzevich, J. C., Graham, L. V., Fernandez, A. P., Aggarwal, R., Rieger, K., Page, K. M., Li, X., Hyde, C., Rath, N., Sloan, A., Oemar, B., Banerjee, A., . . . Vleugels, R. A. (2025). Efficacy, safety, and target engagement of dazukibart, an IFNβ specific monoclonal antibody, in adults with dermatomyositis: a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial. The Lancet, 405(10473), 137–146. https://doi.org/10.1016/s0140-6736(24)02071-3