Rilonacept (IL-1 Trap/Arcalyst) is a long-acting
interleukin-1 (IL-1) blocker developed by Regeneron
Pharmaceuticals. Initially, Regeneron entered into a joint development effort with Novartis to develop
rilonacept for the treatment of
rheumatoid arthritis (RA) but this was discontinued following the review of phase II clinical data showing that
IL-1 blockade appeared to have limited benefit in RA. In February 2008, Regeneron received Orphan Drug approval from the Food and Drug Administration for
rilonacept in the treatment of two
cryopyrin-associated periodic syndromes (CAPS) disorders, namely,
familial cold-induced autoinflammatory syndrome (FCAS) and
Muckle-Wells syndrome (MWS), for children and adults 12 years and older. CAPS is a group of inherited inflammatory disorders consisting of FCAS, MWS,
neonatal-onset multisystem inflammatory disease (
NOMID), also known as chronic infantile neurologic, cutaneous and articular (
CINCA) syndrome, all associated with heterozygous mutations in the NLRP3 (CIAS1) gene, which encodes the
protein NLRP3 or cryopyrin. Prior to the discovery of the NLRP3 (CIAS1) mutations and the advent of IL-1-targeted
therapy, treatment was aimed at suppressing
inflammation but with limited success. The dramatic success of selective blockade of IL-1beta, initially with the
IL-1 receptor antagonist (IL-1Ra;
Kineret(R) or
anakinra/ Amgen, Inc.), not only provided supportive evidence for the role of IL-1beta in CAPS but also demonstrated the efficacy of targeting IL-1beta for treatment of these conditions. A high-affinity
protein called
rilonacept has been produced by
cytokine Trap technology and was developed by Regeneron. The desirable longer half-life of
rilonacept offers potential alternatives to patients who do not tolerate daily
injections very well or have difficulty with drug compliance. The initial evidence for the beneficial effects of
rilonacept for MWS and FCAS suggests that it would also be a suitable treatment for CNICA/
NOMID. It is yet to be determined whether
rilonacept would be an effective treatment for other chronic inflammatory conditions such as
gout,
familial Mediterranean fever and systemic
juvenile idiopathic arthritis.