Targeting the Root: IFNβ Inhibition Shows Promise in Dermatomyositis
- Zili Zhou
- Jul 22
- 2 min read
Original Article: Efficacy, safety, and target engagement of dazukibart, an IFNβ specific monoclonal antibody, in adults with dermatomyositis: a multicentre, double-blind, randomized, placebo-controlled, phase 2 trial
What are the key takeaways of this article?
This phase 2 multicentre, double-blind, randomized, placebo-controlled trial investigated the efficacy, safety, and target engagement of dazukibart, a novel monoclonal antibody targeting interferon beta (IFNβ), in adults with moderate-to-severe dermatomyositis. Dermatomyositis is a chronic autoimmune disease characterized by muscle weakness and distinctive skin rashes, often driven by dysregulation in the type I interferon (IFN) pathway. Existing treatments rely on broad immunosuppression, which often has moderate efficacy and well-known adverse events. There is a substantial need for targeted therapies in dermatomyositis. Dazukibart is a humanized IgG1 monoclonal antibody that selectively neutralizes IFNβ.
The study enrolled 75 adults, aged 18-80 with confirmed dermatomyositis as determined by the expert investigators, across 25 university-based hospitals and outpatient sites (one site in Germany, one in Hungary, two in Poland, two in Spain, and 19 in the USA). These 75 participants were randomly assigned to receive intravenous dazukibart at either 150 mg or 600 mg, or placebo every four weeks, with some participants undergoing a treatment switch at week 12. There were 57 participants in the skin-predominant cohort and 18 in the muscle-predominant cohort.
Results showed that dazukibart significantly improved dermatomyositis activity. At 12 weeks, patients (pooled skin full analysis set) receiving 600 mg and 150 mg doses of dazukibart showed mean Cutaneous Dermatomyositis Disease Area and Severity Index-Activity (CDASI-A) score reductions of –19.2 and –16.6 respectively, compared to –2.9 in the placebo group (all p < 0.0001). More than 80% of patients receiving active treatment achieved a greater than 40% reduction in CDASI-A score; improvement persisted up to 16 weeks after the final dose. In the muscle-predominant cohort, participants who received some dose of dazukibart showed improvements in total improvement score (TIS) that were not statistically significant, but were of moderate clinical importance. Many other secondary outcomes were not statistically significant, possibly due to the small sample size within the muscle-predominant cohort (n=18). Unlike the observation made within the skin-predominant cohort, the muscle-predominant participants who received the 600 mg dose of dazukibart did not have a greater reduction in CDASI-A score compared to placebo receivers at 12 weeks.
Biomarker analysis was done to evaluate target engagement. The authors showed that dazukibart treatment led to the downregulation of IFN in skin lesions and higher serum IFNβ levels. Skin biopsies showed improvements in hallmark features of dermatomyositis following treatment.
The safety profile of dazukibart was favorable. Treatment-emergent adverse events were mostly mild, with infections being the most common.
Overall, this trial demonstrated that dazukibart effectively reduced disease activity in adults with dermatomyositis and was well tolerated. The findings suggest that IFNβ inhibition is promising as a novel, targeted therapy for dermatomyositis, especially for patients with skin-predominant disease. The study is initiating its phase 3 trial to further evaluate dazukibart as a treatment option for dermatomyositis.
Publication Date: July 22, 2025
Reference: 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. Fiorentino, David et al. The Lancet, Volume 405, Issue 10473, 137 - 146
Summary By: Zili Zhou
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