Medarex, Inc (PRINCETON, New Jersey), announced that Novartis Pharmaceuticals AG has advanced ACZ885, a fully human monoclonal antibody targeting interleukin-1β (IL-1 β), to a phase III clinical trial for Muckle-Wells syndrome (MWS), an inherited systemic autoinflammatory disease. MWS is a member of a spectrum of rare genetic disorders referred to as CAPS (CIAS1-related autoinflammatory periodic syndromes). Patients suffering from CAPS have elevated levels of IL-1 and chronic, spontaneous systemic inflammation. ACZ885 has led to immediate and long lasting clinical remission in MWS patients through potent and selective blockage of IL-1b. Submissions for regulatory approvals in MWS are planned for 2009. ACZ885 has a potentially important role in treating a range of systemic inflammatory diseases, and phase II trials are under way in systemic juvenile arthritis and other conditions.

Owing to this advancement, Medarex expects to receive an undisclosed milestone payment from its licensing partner, Novartis. The antibody was generated using Medarex's UltiMAb® technology as part of the company's collaboration with Novartis. Medarex may receive future milestone payments and royalties should this product candidate progress through clinical development and achieve commercial sales.

MWS affects approximately 10,000 people worldwide, and is characterized by mutations in the CIAS1 (cold-induced autoinflammatory syndrome 1) gene. This gene encodes the protein cryopyrin and is involved in regulation of IL-converting caspase-1. CIAS1 belongs to the CATERPILLER family of genes, of which >20 genes are involved in regulating apoptosis or inflammation. MWS is characterized by a range of symptoms, from fever and chills to swollen, painful joints, hives and itchy skin, and progressive hearing loss. A striking feature of MWS is that cold temperature exposure can provoke a major inflammatory episode occurring within hours. MWS is considered to be one of the more severe examples of autoinflammatory disease, and some patients suffer from kidney failure. One of the disease's severe complications, amyloidosis, is often fatal.

Systemic autoinflammatory diseases are characterized by episodes of seemingly unprovoked inflammation, but without the production of high-titer autoantibodies or antigen-specific T-cells. In addition to MWS, a number of autoinflammatory diseases are inherited as Mendelian traits, including familial Mediterranean fever (FMF), TNF receptor-associated periodic syndrome (TRAPS), hyperimmunoglobulinemia D with periodic fever syndrome (HIDS), neonatal-onset multisystem inflammatory disease (NOMID; also known as chronic infantile neurologic, cutaneous, and articular syndrome [CINCA]), familial cold autoinflammatory syndrome (FCAS), pyogenic arthritis with pyoderma gangrenosum and acne (PAPA) syndrome, and Blau syndrome.

—A Techman