This approval was based on two Phase III trials in SJIA patients, aged 2-19, showing significant improvement in the majority of Ilaris-treated patients. Study 1 showed that 84% of patients treated with one subcutaneous dose of Ilaris achieved the primary endpoint of the adapted pediatric American College of Rheumatology 30 (ACR30), compared to 10% achievement of ACR30 for placebo at Day 15. In the open-label part of Study 2, 92 of 128 patients attempted "corticosteroid tapering". Of those 92 patients, 62% were able to substantially reduce their use of corticosteroids, and 46% completely discontinued corticosteroids. In the controlled portion of Study 2, there was a 64% relative reduction in the risk of flare for patients in the Ilaris group as compared to those in the placebo group (hazard ratio of 0.36; 95% CI: 0.17 to 0.75).
"In the US, this approval marks the second Ilaris indication for patients living with rare, autoinflammatory conditions," said Timothy Wright, MD, Global Head of Development, Novartis Pharmaceuticals. "We are committed to studying Ilaris in other IL-1 beta mediated inflammatory diseases, including several rare diseases for which treatment options do not currently exist."
SJIA affects 5-15 children per 100,000 in the United States,and is the most severe subtype of juvenile idiopathic arthritis-. Although the disease can be life-threatening, treatment options are limited. Corticosteroids are often used to treat symptoms and pain despite their long term use being associated with potentially serious adverse effects, including Cushing syndrome, growth suppression and osteoporosis,,.
Ilaris is being investigated in a number of rare autoinflammatory conditions, including Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS), colchicine-resistant Familial Mediterranean Fever (FMF) and Hyper IgD Syndrome (HIDS). Ilaris is considered an investigational agent for these conditions at this point in time. As such, the role that Ilaris could play in treating these conditions and potential benefit to patients is still being determined.
About the Pivotal Phase III Studies
Study 1, a 4-week, randomized, double-blind, placebo-controlled study, involved 84 patients between the ages of 2 and 19 years with active SJIA,. Patients were treated with either a single subcutaneous dose of Ilaris (4 mg/kg, up to 300 mg) (n=43) or placebo (n=41). The primary endpoint was the proportion of patients achieving the adapted pediatric American College of Rheumatology (ACR) 30 response criteria and resolution of fever from baseline at Day 15. This means that patients had at least a 30% improvement in systemic and arthritic symptoms versus baseline. The study met its primary endpoint.
Study 2, a two-part study, had an open-label, single-arm active treatment in Part I followed by a randomized, double-blind, placebo-controlled, event-driven withdrawal design in Part II. A total of 177 patients between the ages of 2 and 19 years with active SJIA were enrolled in the study. Some of these patients had previously participated in the Study 1. In Part I, patients received a subcutaneous dose of Ilaris (4 mg/kg, up to 300 mg) every 4 weeks. The primary endpoint of Part I was to assess whether treatment with Ilaris allowed successful tapering of corticosteroids in at least 25% of SJIA patients who entered the study using a corticosteroid.
In Part II of the study, patients were randomized to either continue receiving Ilaris, or to receive placebo every 4 weeks ("placebo-after-Ilaris group"), until a pre-specified number (37) of flare-events ("flares") had occurred. The primary endpoint of Part II was to demonstrate that the time to flare was longer with Ilaris than with placebo.
The primary endpoints for Study 1 and Study 2 were all met.
Ilaris is a selective, fully human, monoclonal antibody that inhibits IL-1 beta, which is an important part of the body's immune system defenses. Excessive production of IL-1 beta plays a prominent role in certain inflammatory diseases. Ilaris works by neutralizing IL-1 beta for a sustained period of time, therefore inhibiting inflammation.
In addition to its approval for SJIA in the US, Ilaris is approved in the EU for the treatment of refractory gouty arthritis, and in more than 60 countries, including in the EU, US, Switzerland and Japan for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), a rare, lifelong, genetic disorder with debilitating symptoms. The approved indication may vary depending upon the individual country.
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1. Ilaris [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2013.
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