Regeneron Pharmaceuticals, Inc (TARRYTOWN, New York), a fully integrated biopharmaceutical company, announced that treatment with Arcalyst^® (rilonacept), also known as IL-1 Trap, in a phase II study of gout patients initiating therapy with allopurinol to lower their uric acid levels, produced a statistically significant reduction versus placebo in the incidence of gout flares. In the 83-patient, double-blind, placebo-controlled study, the mean number of flares per patient over the first 12 weeks of urate-lowering therapy was 0.79 with placebo and 0.15 with the drug (P = .0011), an 81% reduction, and the primary endpoint of the study. All secondary endpoints were met with statistical significance. Based upon these results, a phase III clinical development program will be initiated early in 2009 with Arcalyst in the prevention of gout flares in patients initiating urate-lowering drug therapy.

Study patients received an initial 320 mg dose, followed by weekly doses of 160 mg. In the first 12 weeks of treatment, 45.2% of patients treated with placebo experienced a gout flare, of whom 47.4% had more than one flare. Among patients treated with the drug, 14.6% experienced a gout flare (P = .0037 vs placebo) and none had more than one flare. No serious drug-related adverse events were reported in patients receiving the study drug; injection-site reaction was the most commonly reported adverse event.

Chronic treatment with uric acid-lowering medicines, such as allopurinol, is prescribed to eliminate and prevent the formation of uric acid crystals. During the first months of allopurinol therapy while uric acid blood levels are being reduced, the break up of the uric acid crystals can result in stimulation of inflammatory mediators, including interleukin-1 (IL-1), resulting in acute flares of joint pain and inflammation. These painful flares make it difficult for patients to stick with treatment. Currently, colchicine or anti-inflammatory drugs are recommended for use to reduce the risk of gout flares in patients taking allopurinol. However, the side effects associated with prophylactic dosing with colchicine, which include diarrhea, abdominal cramps, nausea, and vomiting, can limit patients' adherence to both colchicine and allopurinol treatment. Study results suggest that concomitant use of Arcalyst by subcutaneous injection during the first several months of allopurinol therapy may help avoid gout flares.

Arcalyst is designed to attach to and neutralize IL-1 in the blood stream before the IL-1 can attach to cell-surface receptors and generate signals that can trigger inflammation in a variety of diseases. It is approved for the treatment of cryopyrin-associated periodic syndromes (CAPS), including familial cold auto-inflammatory syndrome, and Muckle-Wells syndrome in adults and children ≥12. CAPS are generally caused by autosomal-dominant mutations in the NLRP-3 (previously known as CIAS1) gene and resultant alterations in the protein cryopyrin, which it encodes. These alterations in cryopyrin lead to over-production of IL-1, resulting in an inflammatory response and the symptoms of CAPS.