ACZ885 Phase III Data Show Rapid, Sustained Clinical Remission In Children And Adults Suffering From A Group Of Rare Autoinflammatory Diseases

New Phase III data demonstrate that ACZ885 (canakinumab), a biological drug in development, achieved rapid and long-lasting clinical remission after just one dose in children and adults with a group of rare but potentially life-threatening autoinflammatory diseases called Cryopyrin-Associated Periodic Syndromes (CAPS)1. Due to the long duration of response, patients only needed further treatment every two months1.


In addition, 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 treated with ACZ885 achieved substantial clinical improvement within 15 days2.


The data, presented at the American College of Rheumatology (ACR) meeting in San Francisco, confirm the potential of ACZ885 to fulfill an unmet medical need in the treatment of autoinflammatory diseases, which can cause life-long debilitating symptoms and potentially fatal complications3.


"The results for ACZ885 are exciting for patients and for the medical community," said Professor Philip Hawkins of the National Amyloidosis Centre at the Royal Free and University College Medical School, London. "Current treatments are not always effective, and are also short-acting and often poorly tolerated by patients. The rapid and long-lasting remission induced by ACZ885 is an important and much-needed development for both children and adults with CAPS."


The significant findings are based on the selective mechanism of action of ACZ885, a fully human monoclonal antibody. Unlike other agents, ACZ885 solely blocks interleukin-1?? (IL-1??), the form of the interleukin-1 protein that sustains autoinflammatory diseases such as CAPS.


CAPS, including Muckle-Wells Syndrome, are characterized by a single gene mutation that activates excessive production of IL-1??. This leads 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 accumulations of amyloidosis (a protein) in kidneys causing dialysis or transplantation3.


IL-1?? is also thought to play a pivotal role in Systemic Juvenile Idiopathic Arthritis (SJIA)4, 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 care4.















"Children and adults affected by these inflammatory diseases have to cope daily with very distressing and debilitating symptoms," said Trevor Mundel, MD, Head of Global Development Functions at Novartis Pharma AG. "We are extremely encouraged by these results that highlight the potential of ACZ885 to address the enormous unmet need in patients with these conditions."


The potential of ACZ885 is reflected in its broad development program. In addition to the studies in CAPS and SJIA, it is also being investigated in more common inflammatory diseases such as rheumatoid arthritis (RA), which affects up to 1% of the world's population5. Studies are currently under way in RA using an innovative tailored approach with biomarkers to predict response to treatment. If successful, these will give suitable patients a personalized approach to the treatment of their disease.


The six-month CAPS clinical trial presented at ACR involved patients aged nine to 74 years old and was divided into three parts. In the first part lasting two 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 response1.


After this, 31 patients who maintained their response proceeded to part two, a randomized six-month, double-blind, placebo-controlled withdrawal design study. Patients were treated every two months and if a relapse occurred, they discontinued and entered part three1.


Part two of the study included the primary endpoint, a comparison between the number of patients treated every two months with ACZ885 who experienced disease outbreaks or 'flares' vs. 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