bmod molecule_300x500Blisibimod is a selective peptibody antagonist of the B-cell activating factor (BAFF) cytokine, also known as B lymphocyte stimulator (BLyS), which is initially being developed as a treatment for lupus. BAFF is a member of the tumor necrosis factor family and is critical to the development, maintenance and survival of B-cells and plasma cells. It is primarily expressed by macrophages, monocytes and dendritic cells and interacts with three different receptor subtypes expressed predominantly on B-cells and plasma cells including BAFF receptor (BAFF-R), B-cell maturation antigen (BCMA), and transmembrane activator and cyclophilin ligand interactor (TACI).

Blisibimod was developed as an alternative to antibodies and is produced in Escherichia coli. Blisibimod may offer a number of potential advantages over other BAFF antagonists such as:

  • Tetravalent BAFF binding domains which give rise to 120-350-fold higher avidity for blisibimod than reported for monoclonal antibodies
  • The ability to bind to both membrane-bound and soluble BAFF
  • Dosing flexibility with both subcutaneous and intravenous routes of delivery
  • Lower molecular weight providing more drug per 200mg weekly dose
  • Distinct intellectual property as a peptibody (relative to antibody and antibody-fragments)

BAFF Involvement in Survival and Maturation of B-cells and plasma cells

Blisibimod Action


IgA nephropathy (also known as Berger’s disease) is the most common cause of primary glomerulonephritis worldwide, occurring more frequently in Asia than in Europe or North America. IgAN is characterized by IgA deposition in the kidney causing blood and protein to leak into the urine. The disease typically progresses slowly but as many as 40-50% of adults will eventually develop end-stage-renal disease and require dialysis or kidney transplant. The current management of IgAN is non-specific treatment aimed at blood pressure control and reduction of proteinuria with angiotensin converting enzyme inhibitors (ACEI) and/or angiotensin II receptor blockers (ARBs). Corticosteroids and immunosuppressive therapy are used in some patients. However, recent data from the STOP-IgAN study showed the addition of immunosuppressives to standard-of-care did not significantly improve outcomes.

Evidence for a role of BAFF in IgAN disease pathology is observed in patients and animal models. Elevated serum concentrations of BAFF are reported in patients with IgAN, and these correlate with histological disease severity.  In addition, BAFF is known to stimulate the production of immunoglobulins, and mice that over express BAFF have elevated levels of circulating IgA along with IgA deposits in the kidney. Collectively, these data provide the basis for the use of blisibimod as the first potential targeted therapy to reduce production of IgA-containing immune complexes and thereby prevent kidney damage and disease progression.


Anthera is currently conducting one study with Blisibimod.

Bright•SC: The primary objective of this study is to evaluate the clinical efficacy of blisibimod as a treatment for IgA Nephropathy. Learn more.

Print Friendly