Gevokizumab Overview

Introduction of Gevokizumab

Gevokizumab (XOMA 052) (Box 1) is a potent monoclonal antibody (mAb), developed by XOMA Corporation, with unique allosteric modulating properties and the potential to treat patients with a wide variety of diseases. Gevokizumab binds strongly to interleukin-1 beta (IL-1β), a pro-inflammatory cytokine, which has been implicated in cardiovascular conditions, lung cancer, and auto-inflammatory diseases. Gevokizumab has been used in trials studying the treatment of acne vulgaris, osteoarthritis, Bechet’s uveitis, pyoderma gangrenosum, and Bechet’s disease uveitis, among others. On August 25, 2017, XOMA Corporation licensed the global commercial rights to gevokizumab to Novartis. Under the license agreement, Novartis will have worldwide rights to gevokizumab, and will be solely responsible for the development and commercialization of antibodies and products containing antibodies arising from gevokizumab. XOMA received an approximately $16 million upfront payment, and Novartis repaid in its entirety the approximately €12 million of debt owed by XOMA to Les Laboratoires Servier. XOMA is eligible to receive up to $438 million in development, regulatory and commercial milestones plus tiered high-single to mid-double-digit royalties on net sales of gevokizumab. Novartis is exploring options for Gevokizumab development as part of its pharmaceutical portfolio.

Mechanism of Action of Gevokizumab

Gevokizumab can neutralize human IL-1β by binding to it. IL-1 is a proinflammatory cytokine that plays a role in the immune response to microorganisms, trauma and stress, while this cytokine is additionally involved in tissue destruction and fibrosis. There are two distinct IL-1 genes encoding the production of IL-1α and IL-1β, namely gene IL1A and IL1B. IL-1 receptor type 1 (IL-1R1) is a virtually ubiquitous cell-surface receptor. Each IL-1 binds to this receptor. After binding, IL-1 triggers a cascade of inflammatory mediators, chemokines and other cytokines. Gevokizumab competes with IL-1R1 to bind to IL-1β and inhibits the IL-1β/IL-1R1 induced downstream pathways. In terms of novel mechanism, the action of gevokizumab does not involve simple competitive receptor binding but allows a context-dependent attenuation of ligand activity. This is ascribed to the fact that the epitope of gevokizumab is proximal to, but does not overlap with, the receptor interface, without specifically inhibiting the region required for receptor binding. Indeed, two of the residues of IL-1b that are important for XOMA 052 binding (E96 and K97) are located in the G loop of the mature IL-1b protein, which is adjacent to the region that contacts the receptor, and a part of this loop is important for receptor binding. The third residue important for XOMA 052 binding (Q116) is located near this loop, and gevokizumab is the first reported example of a therapeutic antibody binding to this region. Finally, the magnitude of the diminution in signaling as accomplished by gevokizumab is independent of antibody concentration, provided all available IL-1b are bound. Under this condition, signaling output depends on the concentrations of ligand and the other components of the signaling system (e.g., IL-1Rα, IL-1 receptors, etc.). As a result, very low receptor occupancy can achieve efficacious signaling transduction.

Fig.1 Mechanism of action of Gevokizumab

What We Provide

Therapeutic Antibody

Gevokizumab

We provide high-quality Gevokizumab for use in WB, FC, IP, ELISA, Neut, FuncS, IF and most other immunological methods. For lab research use only, not for diagnostic, therapeutic or any in vivo human use.

For research use only. Not intended for any clinical use.