Briakinumab

Abstract

Although limited by small sample sizes, length of follow-up, and a lack of direct comparisons with other psoriasis treatments, initial data regarding the safety and efficacy of briakinumab for the treatment of psoriasis is promising. Ongoing Phase III trials may provide additional information regarding the relative efficacy and safety of briakinumab.

Development in the cynomolgus macaque following administration of ustekinumab, a human anti‐il‐12/23p40 monoclonal antibody, during pregnancy and lactation

“…Abnormal regulation of IL-12 and IL-23 is associated with a variety of immune-mediated human diseases, including psoriasis, Crohn's disease, rheumatoid arthritis, ulcerative colitis, and others (Barrie and Plevy, 2005;Elliott et al, 2009;Veldman, 2006). Monoclonal antibodies in development that antagonize the actions of both IL-12 and 23 through p40 inhibition include ustekinumab (CNTO 1275, Centocor Research and Development, Inc.) (Gottlieb et al, 2009;Scanlon, 2009;Weber and Keam, 2009) and briakinumab (ABT 874, Abbott Laboratories) (Ding et al, 2008;Lima et al, 2009). A small molecule intracellular inhibitor of IL-12 and IL-23 production, apilimod (STA-5326, Synta Pharmaceuticals) (Burakoff et al, 2006), is also in development.…”

Pharmacokinetic de-risking tools for selection of monoclonal antibody lead candidates

“…30 The solution dynamics of the antibody are critical for its function (e.g., antigen binding, complement activation) and may also influence pharmacokinetic properties, e.g., due to intraand inter-domain interactions as observed by Schoch et al 31 They used molecular dynamic (MD) simulations over a period of 100 ns to study the effect of net charge on IgG-FcRn interaction. They analyzed 2 IgG1 monoclonal antibodies, ustekinumab (Stelara Ò ) with elimination half-life of 22 days 32 and briakinumab (ABT874) with elimination half-life of 8-9 days, [33][34][35] and observed that during the course of the MD simulation one of the 2 antigen-binding fragments (Fabs) of briakinumab approached FcRn and persisted in that confirmation for the rest of the simulation. In contrast, the Fabs of ustekinumab did not approach FcRn over the course of the simulation.…”

Insights into IL-23 biology: From structure to function

“…Briakunumab is another antibody targeting the p40 subunit, which is currently in clinical phase III [128]. Both monoclonal p40 antibodies have been extensively investigated in pre-clinical and clinical studies for the treatment of several autoimmune diseases [9].…”