Biologic Differences Between Various Inhibitors of the BLyS/BAFF Pathway: Should We Expect Differences Between Belimumab and Other Inhibitors in Development?

For the first time in more than 50 years, the US Food and Drug Administration has approved a drug specifically for the treatment of systemic lupus erythematosus (SLE). This drug, belimumab, is a monoclonal antibody that neutralizes the B-cell survival factor, B-lymphocyte stimulator (BLyS). Although belimumab has demonstrated a very favorable safety profile, many SLE patients have failed to clinically improve from belimumab therapy. Three additional BLyS antagonists (atacicept, blisibimod, tabalumab) are currently undergoing clinical testing. These antagonists subtly differ from belimumab in their biologic targets, and each is administered through a route (subcutaneous) that differs from the route through which belimumab is currently delivered (intravenous). Whether these differences will have meaningful consequences for efficacy and safety remains to be determined.