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Rilonacept—CAPS and Beyond

A Scientific Journey


Address for correspondence: Neil Stahl, Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591. Voice: 914 345 7400; fax: 914 345 7650.


Rilonacept is a dimeric fusion protein consisting of the extracellular domains of interleukin (IL)-1 type 1 receptor and IL-1 receptor accessory protein joined to the constant region (Fc) of human immunoglobulin G1. By incorporating both components of the IL-1 binding complex, rilonacept is able to tightly bind IL-1 with picomolar affinity. Although early clinical results in rheumatoid arthritis (RA) suggested that RA is not primarily an IL-1-driven disease, the discovery that the rare genetic conditions called cryopyrin-associated periodic syndromes (CAPS) were caused by overproduction of IL-1 led to clinical development and approval for these conditions. An assay that detects rilonacept:IL-1 complexes in plasma is helping to identify new indications, such as gout, in which IL-1 overproduction plays a key pathogenic role. The development of rilonacept for CAPS was achieved through collaboration between the pharmaceutical industry, academia, and government agencies, and demonstrates that knowledge gleaned in orphan indications can inform drug development for more common and heterogeneous diseases.