Dazukibart shows promise as treatment for dermatomyositis

Key takeaways:

• The study included patients with cutaneous dermatomyositis and those with muscle involvement.
• Treatment-emergent adverse events occurred in 80% and 81% of dazukibart 150 mg and 160 mg groups.

Dazukibart, a type I interferon inhibitor, reduced dermatomyositis disease severity while maintaining a well-tolerated safety profile among patients, according to a study.

“Dermatomyositis is a chronic systemic autoimmune disease characterized by distinctive cutaneous eruptions, muscle weakness and other systemic manifestations including interstitial lung disease,” David Fiorentino, MD, PhD, professor of dermatology at Stanford University School of Medicine, and colleagues wrote. “Studies have shown that type I interferon (IFN) inducible genes are overexpressed in blood, skin and muscle tissue of patients with dermatomyositis compared with healthy people and those with other inflammatory skin and muscle diseases. In dermatomyositis skin, IFN-beta and IFN-gamma transcript levels are correlated with the IFN transcriptional response.”

A potent, selective, monoclonal antibody called dazukibart (Pfizer) has the ability to bind to IFN-beta and prevent signaling of the IFN-alpha/beta receptor, positioning it as a potentially effective treatment for dermatomyositis.

Study design

To evaluate the efficacy and safety of this treatment option, the researchers conducted a double-blind, placebo-controlled, phase 2 trial composed of 75 adults with dermatomyositis from 25 sites in Germany, Hungary, Poland Spain and the U.S.

Each participant was randomly assigned intravenous treatment of dazukibart 150 mg (n = 15), 600 mg (n = 37) or placebo (n = 23) in various stages of the study.

In stage 1, patients with cutaneous involvement only were treated with dazukibart 600 mg or placebo, followed by the addition of dazukibart 150 mg in stage 2. In stage 2a the same group received dazukibart 600 mg then placebo, dazukibart 150 mg then placebo, placebo then dazukibart 600 mg, or placebo then dazukibart 150 mg.

Stage 3 subjects, comprised of those with muscle involvement (n = 18), were treated with dazukibart 600 mg then placebo or placebo then dazukibart 600 mg. The switching of dosages in the stage 2a and 3 groups occurred at week 12.

Study results

According to Cutaneous Dermatomyositis Disease Area and Severity Index-Activity (CDASI-A) scores, patients with cutaneous involvement only that were treated with dazukibart 600 mg saw an –18.8 (90% CI, –21.8 to –15.8) change from baseline in disease severity by week 12, whereas the placebo group saw a –3.9 (90% CI, –8.5 to –0.6) change.

Pooled results showed a –19.2 (90% CI, –21.5 to –16.8) and –16.6 (90% CI, –19.8 to –13.4) change in CDASI-A scores from baseline among those treated with dazukibart 600 mg and 150 mg, respectively, by week 12 vs. a –2.9 (90% CI, –6.3 to 0.5) change among placebo-treated patients. According to the study, these improvements persisted through 24 weeks, 16 weeks after the last dose.

Subjects of the muscle-involvement group that were treated with dazukibart 600 mg saw higher total improvement scores vs. those treated with placebo at week 12 (56.4; 90% CI, 41.4 to 71.4 vs. 36.9; 90% CI, 21.9 to 52).

Safety findings

Treatment-emergent adverse events occurred in 80%, 81% and 78% of dazukibart 150 mg, dazukibart 160 mg and placebo groups, respectively. The most common treatment-emergent adverse events were infections and infestations which occurred in 13%, 32% and 30% of the respective groups.

Serious adverse events occurred in four of the dazukibart 150 mg-treated patients and one in the placebo group. A stage 3 patient receiving dazukibart 600 mg followed by placebo died of hemophagocytic lymphohistiocytosis and macrophage activation syndrome during follow-up, deemed unlikely related to the study medication.

“The results showed that dazukibart had a rapid and pronounced reduction in disease activity in patients with dermatomyositis,” the authors concluded. “These findings support inhibition of IFN-beta as a novel and highly promising therapeutic strategy in patients with dermatomyositis.”