Rilonacept

Description

The symptoms of inherited autoinflammatory syndromes, which include recurrent fever, joint pain, and rash, are a result of the aberrant signaling of the proinflammatory cytokine IL-1β. As the central component of the cryopyrin inflammasome, excess cryopyrin leads to stimulation of the inflammasome resulting in the activation of the other major component of the inflammasone, caspase 1, which is responsible for the processing of proIL-1β to its functional form. Rilonacept’s mechanism of intervention in the pathogenesis of CAPS is the blockade of the excessive IL-1β signaling. As an engineered fusion protein, rilonacept combines the extracellular binding domains of the human IL-1 receptor component (IL-1R1) and IL-1 receptor accessory protein (IL-1RAcP) in a single chain, with two of these chains joined to the Fc portion of human immunoglobulin G (IgG) creating a dimeric molecule. Rilonacept serves as an effective soluble IL-1β sink or trap since the coupled receptor components bind IL-1βwith higher affinity than either individual receptor. The equilibrium dissociation constants for IL-1b and IL-1a are 0.5 and 1.4 pM, respectively. Compared to other IL-1 antagonists, rilonacept may provide improved efficacy with its offering of dual receptor occupancy; agents containing a single soluble receptor have been hypothesized to potentially induce immune responses since IL-1 exerts its signaling through a multi-component receptor system. Likewise, drugs that target only one of the components, such as the IL-1R1 antagonist anakinra, have been less effective in treating CAPS, possibly due to receptor occupancy issues.

Originator

Regeneron (United States)

Uses

Treatment of rheumatoid arthritis, autoinflammatory diseases, and osteoarthritis.

brand name

Arcalyst

IC 50

IL-1

Raw materials

Preparation Products