Chemistry:Dazukibart
Dazukibart (previously known as PF-06823859) is a humanized monoclonal antibody developed by Pfizer for the treatment of autoimmune diseases, particularly dermatomyositis and systemic lupus erythematosus.[1] It is classified as a potent, selective, humanized IgG1 neutralizing monoclonal antibody that specifically targets interferon beta (IFN-β).[2]
Mechanism of action
Dazukibart functions by neutralizing interferon beta-1 (IFNB1), a type I interferon that plays a critical role in autoimmune inflammation.[3] The drug targets the dysregulated type I interferon pathway that is characteristic of several autoimmune conditions, particularly dermatomyositis, where IFN-β rather than IFN-α has been identified as the predominant elevated interferon.[4]
Administration and dosing
Dazukibart is administered through intravenous infusion, though subcutaneous formulations are also being investigated.[3] The drug is currently being evaluated in ongoing clinical trials to determine optimal dosing regimens for different indications.
Clinical development
Phase I studies
Initial safety and pharmacokinetic studies of dazukibart (then known as PF-06823859) were published in 2020, demonstrating an acceptable safety and tolerability profile in healthy volunteers. These studies supported its continued development for disorders associated with increased interferon β levels.[5]
Phase II studies
A landmark phase 2 clinical trial published in The Lancet in January 2025 demonstrated significant efficacy of dazukibart in treating adults with moderate-to-severe dermatomyositis. The multicentre, double-blind, randomized, placebo-controlled study was conducted across 25 sites in Europe and the USA.[1][4] The study showed that both 150 mg and 600 mg IV doses every 4 weeks met the primary endpoint of significantly decreasing CDASI-A scores at 12 weeks compared with placebo, with dazukibart resulting in a pronounced reduction in disease activity and being generally well tolerated.[1][6]
Phase III studies
As of 2025, dazukibart has entered Phase 3 clinical trials for the treatment of myositis, indicating advancement toward potential regulatory approval.[7][8]
Therapeutic indications
Dermatomyositis
The primary indication for dazukibart is dermatomyositis, a chronic autoimmune disease characterized by distinctive cutaneous eruptions, muscle weakness, and systemic manifestations including interstitial lung disease. Clinical studies have shown rapid onset of response in adult patients with moderate-to-severe refractory dermatomyositis.[9]
Other indications
Dazukibart is also being investigated for the treatment of systemic lupus erythematosus and polymyositis, conditions that also involve dysregulated type I interferon signaling.[10]
Regulatory status
Dazukibart has received orphan drug designation from the European Medicines Agency (EMA) for the treatment of dermatomyositis (designation EU/3/20/2392), recognizing the significant medical need for effective treatments for this rare autoimmune condition.[11]
References
- ↑ 1.0 1.1 1.2 "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" (in English). Lancet 405 (10473): 137–146. January 2025. doi:10.1016/S0140-6736(24)02071-3. PMID 39798982.
- ↑ "Dazukibart (PF-06823859)". MedChemExpress. https://www.medchemexpress.com/dazukibart.html.
- ↑ 3.0 3.1 "Dazukibart by Pfizer for Systemic Lupus Erythematosus: Likelihood of Approval". Pharmaceutical Technology. January 19, 2025. Retrieved September 4, 2025.
- ↑ 4.0 4.1 "Dazukibart for dermatomyositis: expanding the therapeutic arsenal". Annals of Translational Medicine. June 24, 2025.
- ↑ "Safety, Tolerability, and Pharmacokinetics of PF-06823859, an Anti-Interferon β Monoclonal Antibody: A Randomized, Phase I, Single- and Multiple-Ascending-Dose Study". Clinical Pharmacology in Drug Development 10 (3): 307–316. March 2021. doi:10.1002/cpdd.887. PMID 33352008.
- ↑ "Dazukibart shows promise as treatment for dermatomyositis". Healio. January 27, 2025. Retrieved September 4, 2025.
- ↑ "Dazukibart Recruiting Phase 3 Trials for Myositis Treatment". DrugBank. Retrieved September 4, 2025.
- ↑ Pfizer (2025-08-12). A Phase 3, Multi-Center, Open-Label Extension Study to Investigate the Long-Term Safety, Tolerability, and Efficacy of Dazukibart in Participants With Idiopathic Inflammatory Myopathies (Including Participants With Dermatomyositis or Polymyositis) (Report). clinicaltrials.gov. https://clinicaltrials.gov/study/NCT06698796.
- ↑ "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". ACR Meeting Abstracts. September 1, 2023.
- ↑ "Clinical Trial for Dermatomyositis and Polymyositis". Pfizer Clinical Trials. Retrieved September 4, 2025.
- ↑ "EU/3/20/2392 - orphan designation for treatment of dermatomyositis". European Medicines Agency. May 18, 2021. Retrieved September 4, 2025.
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