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Dazukibart - IFN beta

Dazukibart (PF-06823859) is a humanized IgG1 monoclonal antibody that selectively neutralizes interferon-β (IFN-β), a key upstream component of the type I interferon axis strongly implicated in dermatomyositis (DM) biology.[1–3] By blocking IFN-β, the strategy aims to reduce interferon-stimulated gene activity and downstream chemokine/cytokine amplification that sustains cutaneous and (in some patients) muscle inflammation, offering a more “pathway-specific” alternative to broad immunosuppression.[1] The clinical development program has been led by Pfizer, with phase 2 efficacy/safety data now published and phase 3 programs registered in idiopathic inflammatory myopathies (including DM/PM).[1,4,5]

The pivotal published efficacy dataset is a multicenter, double-blind, randomized, placebo-controlled phase 2 trial conducted at 25 sites across Germany, Hungary, Poland, Spain, and the USA.[1,4] The trial enrolled skin-predominant DM (CDASI-A ≥14 and ≥1 failed systemic therapy) across several stages and also included a muscle-predominant cohort (stage 3) primarily to evaluate safety while exploring muscle-response signals.[1]

At week 12, the primary endpoint in the skin-predominant cohort—change from baseline in CDASI-A—showed large, statistically robust improvements. In stage 1, mean CDASI-A change for dazukibart 600 mg was −18.8 (90% CI −21.8 to −15.8) with a placebo-adjusted difference of −14.8 (−20.3 to −9.4; p<0.0001).[1] In the pooled skin analysis set (stages 1/2/2a), mean CDASI-A change at week 12 was −19.2 for 600 mg (placebo-adjusted difference −16.3, 90% CI −20.4 to −12.1; p<0.0001) and −16.6 for 150 mg (placebo-adjusted difference −13.7, 90% CI −18.3 to −9.0; p<0.0001).[1] Complementary ACR 2023 data emphasized early separation: CDASI-A differentiation from placebo was already evident at week 4 for both 150 mg and 600 mg (placebo-adjusted CFB −13.19 and −12.35, respectively), and itch (5D-itch) improved as early as week 1 in the 600 mg arm.[6]

Safety signals in phase 2 were broadly comparable in frequency across groups but require nuanced interpretation given small sample sizes and severe disease context.[1] Treatment-emergent adverse events occurred in 80% (150 mg), 81%(600 mg), and 78% (placebo), with infections/infestations the most common category (13% vs 32% vs 30%).[1] Serious adverse events were reported in 11% (150 mg) and 4% (placebo).[1] One death occurred in stage 3 follow-up (dazukibart 600 mg then placebo) due to haemophagocytic lymphohistiocytosis/macrophage activation syndrome, underscoring that interferon-pathway manipulation in systemic autoimmunity demands careful pharmacovigilance and phenotype-aware patient selection.[1] Phase 3 studies in active idiopathic inflammatory myopathies (DM/PM) are registered and ongoing (e.g., NCT05895786), positioning dazukibart as one of the more advanced interferon-targeted candidates in IIM development.[5]

References (AMA)

  1. Fiorentino D, Mangold AR, Werth VP, et al. 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. Lancet. 2025;405(10473):137-146. doi:10.1016/S0140-6736(24)02071-3. Available at: https://pubmed.ncbi.nlm.nih.gov/39798982/
  2. Pfizer. Plain Language Study Results Summary (PLSRS): Study C0251002 (PF-06823859 / dazukibart) in dermatomyositis (Phase 2–4). Published October 30, 2023. Accessed January 31, 2026. https://www.pfizer.com/sites/default/files/plsr-studies/C0251002%20Plain%20Language%20Study%20Results%20Summary%20%28PLSRS%29%20Phase%202-4.pdf
  3. The Antibody Society. Dazukibart (PF-06823859) entry (target IFN-β; development stage; sponsor). Accessed January 31, 2026. https://db.antibodysociety.org/db0/1101/
  4. ClinicalTrials.gov. A Study in Adults With Moderate To Severe Dermatomyositis (NCT03181893). Accessed January 31, 2026. https://clinicaltrials.gov/study/NCT03181893
  5. ClinicalTrials.gov. A Study to Understand How PF-06823859 (dazukibart) Works in People With Idiopathic Inflammatory Myopathies (DM and PM) (NCT05895786). Accessed January 31, 2026. https://clinicaltrials.gov/study/NCT05895786
  6. Aggarwal R, Peeva E, Mangold A, Sloan A, Chu M. Rapid onset of response in adult dermatomyositis patients receiving anti-interferon β (PF-06823859): results of a phase 2, double-blind, randomized, placebo-controlled study [abstract]. Arthritis Rheumatol. 2023;75(suppl 9). Accessed January 31, 2026. https://acrabstracts.org/abstract/rapid-onset-of-response-in-adult-dermatomyositis-patients-receiving-anti-interferon-%CE%B2-pf-06823859-results-of-a-phase-2-double-blind-randomized-placebo-controlled-study/