A Comprehensive Monograph on Rilonacept (Arcalyst®)

Executive Summary

Rilonacept, marketed under the brand name Arcalyst®, is a sophisticated biotech therapeutic classified as a dimeric fusion protein and a potent inhibitor of interleukin-1 (IL-1). Engineered as an "IL-1 trap," it functions as a soluble decoy receptor that binds and neutralizes both interleukin-1 alpha (IL−1α) and interleukin-1 beta (IL−1β), key cytokines that drive the pathophysiology of several autoinflammatory diseases. This mechanism directly addresses the underlying inflammatory cascade in its approved indications.

The U.S. Food and Drug Administration (FDA) has approved Rilonacept for three distinct rare diseases. Its initial approval was for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), including Familial Cold Autoinflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS), in patients aged 12 and older. Subsequently, its label was expanded to include the maintenance of remission of Deficiency of Interleukin-1 Receptor Antagonist (DIRA) in patients weighing 10 kg or more. Most recently, it became the first and only FDA-approved therapy for the treatment of Recurrent Pericarditis (RP) and the reduction of recurrence risk in patients aged 12 and older.

Clinical evidence supporting these indications is robust. In pivotal trials for CAPS, Rilonacept demonstrated rapid and near-complete resolution of systemic inflammatory symptoms. The landmark Phase III RHAPSODY trial for Recurrent Pericarditis showed that Rilonacept reduced the risk of disease recurrence by a remarkable 96% and enabled the complete discontinuation of corticosteroids in all patients who were previously dependent on them. For DIRA, an open-label study in a small pediatric cohort showed that Rilonacept effectively maintained inflammatory remission.