Novartis Pharma AG (BASEL, Switzerland) announced that phase III data demonstrate that ACZ885 (canakinumab), a fully-human monoclonal antibody blocking interleukin-1ß (IL-1ß), achieved rapid and long-lasting clinical remission after just one dose in patients with a group of rare but potentially life-threatening autoinflammatory diseases called cryopyrin-associated periodic syndromes (CAPS). Due to the long duration of response, patients only needed further treatment every 2 months. CAPS, including Muckle-Wells syndrome, are characterized by a single gene mutation that activates excessive production of IL-1ß, leading to symptoms such as fever, fatigue, skin rash, painful joints and muscles, and severe headache. In addition, patients can suffer from more debilitating complications like hearing loss and amyloidosis, which may lead to amyloid deposits in the kidneys, necessitating dialysis or transplantation.

Novartis also announced that preliminary results of a phase I/II study in systemic juvenile idiopathic arthritis (SJIA), the most severe form of arthritis in children, showed that most patients (aged 4 to 19 years) treated with ACZ885 achieved substantial clinical improvement (measured by the pediatric ACR50 scale) within 15 days. Importantly, four patients achieved complete remission of the disease. IL-1ß is also thought to play a pivotal role in SJIA, causing symptoms such as destructive arthritis, fever, and rash. Suboptimal treatment can lead to growth retardation and joint and bone disability, as well as developmental and social consequences and life-threatening complications such as macrophage activated syndrome, mostly caused by infections and requiring immediate intensive care.

The 6-month CAPS clinical trial involved patients aged 9 to 74 years old and was divided into three parts. In the first part lasting 2 months, 35 patients received a single dose of ACZ885 by subcutaneous injection. All but one patient (97.1%) showed a rapid and long-lasting clinical and biochemical response. After this, 31 patients who maintained their response proceeded to part two, a randomized 6-month, double-blind, placebo-controlled withdrawal design study. Patients were treated every 2 months, and if a relapse occurred, they discontinued and entered part three.

Part two of the study included the primary endpoint, a comparison between the number of patients treated every 2 months with ACZ885 who experienced flares versus those on placebo. Results showed that no patients in the ACZ885 group experienced a disease flare compared to 81% (13 out 15 patients) in the placebo group (P <.001). Markers of inflammation (C-reactive protein and serum amyloid A) were normalized in patients treated with ACZ885, but increased significantly for those on placebo.

The study is being concluded with a 4-month open-label, active-treatment period to provide further efficacy and safety data. All patients are subsequently being offered the chance to take part in an additional phase III study to provide long-term information about the efficacy and safety of ACZ885.

The most common adverse event reported was upper respiratory tract infection. No deaths or serious adverse events were reported, and there were no discontinuations due to adverse events in the overall study.

In addition to the studies in CAPS and SJIA, studies are currently under way in rheumatoid arthritis and gout using a tailored approach with biomarkers to predict response to treatment with ACZ885.