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83 Biib059, a monoclonal antibody targeting bdca2, demonstrates evidence of proof of biological activity in subjects with cutaneous lupus
  1. R Furie1,
  2. VP Werth2,
  3. JF Merola3,
  4. W Wang4,
  5. D Rabah5,
  6. C Barbey6,
  7. K Smirnakis7,
  8. B Werneburg8,
  9. J Bornstein9,
  10. TL Reynolds11,
  11. L Stevenson10 and
  12. N Franchimont12
  1. 1Northwell Health, Division of Rheumatology, Great Neck NewYork, USA
  2. 2University of Pennsylvania School of Medicine, Department of Dermatology, Philadelphia, Pennsylvania, USA
  3. 3Harvard Medical School, Centre for Skin and Related Musculoskeletal Diseases, Boston, Massachusetts, USA
  4. 4Biogen, Biostatistics, Cambridge, Massachusetts, USA
  5. 5Biogen, Research/Immuno Discovery Biology, Cambridge, Massachusetts, USA
  6. 6Biogen, Biosimilars Medical/Affiliate Medical Affairs/Neurology, Cambridge, Massachusetts, USA
  7. 7Biogen, Drug Safety and Benefit Risk Management, Cambridge, Massachusetts, USA
  8. 8Biogen, US Medical/Global Medical Affairs Neurology, Cambridge, Massachusetts, USA
  9. 9Biogen, Clinical Development/Immunology Drug Innovation Unit, Cambridge, Massachusetts, USA
  10. 10Biogen, Research/In-Vitro Sciences, Cambridge, Massachusetts, USA
  11. 11Biogen, Translational Sciences/Biomolecular and Small Molecule Science, Cambridge, Massachusetts, USA
  12. 12Biogen, Immunology Drug Innovation Unit, Cambridge, Massachusetts, USA

Abstract

Background and aims Type I interferons (IFN-I) are central to the pathogenesis of systemic lupus erythematosus (SLE). BDCA2 is a plasmacytoid dendritic cell (pDC)-specific receptor that, upon engagement, inhibits the production of IFN-I and other inflammatory mediators. In this first-in-patient phase 1b study, biological activity of BIIB059, a humanised anti-BDCA2 monoclonal antibody, was evaluated in SLE subjects with active cutaneous lupus (CLE).

Methods 12 adult SLE subjects with active CLE received a single IV administration of either BIIB059 20 mg/kg (n=8) or placebo (n=4). A panel of IFN-responsive genes (IRG) was assessed from whole blood. Cellular infiltration and expression of MxA and IFITM3 were evaluated in skin biopsies from active lesions at baseline and week 4. CLE disease activity was determined using the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). Safety data were also collected.

Results BIIB059 decreased the expression of IRG in blood and MxA and IFITM3 proteins in skin. CD45+ cells were reduced in skin biopsies of BIIB059-treated subjects. The reduction in inflammatory cells as well as MxA and IFITM3 expression at week 4 correlated with improvement in CLASI activity score at week 12. BIIB059 was well tolerated with no withdrawals due to AEs.

Conclusions The study, confirming the major role played by pDCs in the production of IFN-I in the blood and skin in CLE, supports further development of BIIB059.

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