The EU submission was supported by data showing that Ilaris produced rapid and sustained remission of symptoms in up to 97% of cryopyrin-associated periodic syndrome (CAPS) patients, with most responding from the first injection [2]. Cryopyrin-associated periodic syndrome includes three distinct auto-inflammatory disorders. These are familial cold auto-inflammatory syndrome, the mildest form of cryopyrin-associated periodic syndrome; Muckle-Wells syndrome; and neonatal-onset multisystem inflammatory disease (also known as ‘chronic infantile neurological cutaneous articular syndrome’), the most severe form of the disease [2–3].

Cryopyrin-associated periodic syndrome is believed to occur in approximately 6500 patients worldwide and 2500 patients in the EU [3,6]. However, because of lack of diagnosis or misdiagnosis, fewer than 1000 cases have been officially reported worldwide [1,3].

The symptoms of cryopyrin-associated periodic syndrome (such as debilitating fatigue, rash, fever, headaches, joint pain and conjunctivitis) can be present from birth or infancy and can occur daily throughout patients’ lives [2,3]. Serious long-term consequences can include deafness, bone deformities, erosive joint destruction and central nervous system damage leading to loss of vision [1–3]. Approximately 25% of cryopyrin-associated periodic syndrome patients develop amyloidosis, a condition in which the build-up of proteins can cause vital organs to fail, resulting in renal failure and death within five to ten years [1].

When approved, Ilaris – a monoclonal antibody formerly known as ACZ885 – will be the only treatment in the EU indicated for cryopyrin-associated periodic syndrome patients aged four years and older [1]. Ilaris represents an important advance in the development of personalized medicines because it targets a condition that is triggered by a specific genetic mutation. In cryopyrin-associated periodic syndrome patients, this mutation drives the overproduction of interleukin 1-beta (IL-1ß), which causes the widespread sustained inflammation and tissue damage associated with the disease [3–5].

Because Ilaris normalizes the production of IL-1ß [1–3], it is also being studied in other diseases in which IL-1ß plays a pivotal part, such as systemic juvenile idiopathic arthritis, gout, chronic obstructive pulmonary disorder, and type 2 diabetes.

’By concentrating initially on a rare syndrome with a well-defined disease process such as CAPS, we have been able to demonstrate a clear therapeutic advantage with Ilaris,’ said Trevor Mundel, MD, Head of Global Development at Novartis Pharma AG. ’Our focus now is to establish whether this could also provide a new approach to the treatment of other diseases involving a similar underlying process.’

The Ilaris filing was based on a clinical trial program involving more than 100 cryopyrin-associated periodic syndrome patients. The pivotal study is a three-part, one-year Phase III study involving 35 patients aged nine to 74 years old with varying degrees of disease severity [2]. Results for the primary endpoint showed that none of the patients treated with Ilaris (0 out of 15) experienced a disease outbreak or ‘flare’ compared with 13 of the 16 patients who received placebo (0% vs 81%, respectively) [2].

References

1 National Horizon Scanning Centre. Canakinumab for cryopyrin associated periodic syndrome. November 2008. Available at: http://www.pcpoh.bham.ac.uk/publichealth/horizon/outputs/documents/2008/sept-dec/Canakinumab.pdf 2. Last accessed April 21, 2009
2 Lachmann, H.J. et al. (2009) Use of canakinumab in the cryopyrin-associated periodic syndrome. N. Engl. J. Med., 360
3 Durrant, K.L.W. et al. CAPS cryopyrin-associated periodic syndromes 2008. Available at: http://www.nomidalliance.net/Download1.html. Last accessed April 19, 2009
4 Joost, P.H. et al. (2006) The inflammasome – a linebacker of innate defense. N. Engl. J. Med. 355, 730–732
5 Lachmann, H.J. et al. (2009) In vivo regulation of interleukin 1 in patients with cryopyrin-associated periodic syndromes. J. Exp. Med. Published online April 13, 2009. Available at www.jem.org/cgi/doi/10.1084/jem.20082481
6 European Medicines Agency (EMEA). Pre-authorisation evaluation of medicines for human use. Committee for orphan medicinal products. Available at: www.emea.europa.eu/pdfs/human/comp/opnion/17086808en.pdf. Last accessed 14 July 2009