The accelerated EU decision follows approvals in the US and Switzerland, where Ilaris was granted priority review. Ilaris is the only medicine approved in the EU for cryopyrin-associated periodic syndrome (CAPS) patients as young as four years old and for patients with the most debilitating form of CAPS, neonatal-onset multisystem inflammatory disease (NOMID) [1]. Ilaris is a fully human monoclonal antibody given by injection under the skin once every two months – the longest dosing interval of any available treatment [2,3,4].

‘Initially we studied Ilaris in a very rare disease with a well-understood genetic profile, and now that its efficacy has been proven, we are able to move ahead rapidly with development in other diseases characterized by the same inflammatory process,’ said Joe Jimenez, CEO of the Novartis Pharmaceuticals Division.

The regulatory submission was supported by data showing that Ilaris produced rapid and sustained remission of symptoms in up to 97% of CAPS patients, with most of them responding within hours of the first injection [2].

Ilaris, previously known as ACZ885, targets and normalizes the production of a protein within the immune system called interleukin-1 beta (IL-1ß) [5,6,7]. In CAPS patients, IL-1ß is overproduced, causing widespread inflammation and tissue damage [6,8,9]. Symptoms – such as debilitating fatigue, fever, joint pain and conjunctivitis – can be present from infancy and continue throughout the patients’ life [2,6].

If left untreated, CAPS can have serious consequences such as deafness, bone deformities, erosive joint destruction and central nervous system damage leading to loss of vision [2,5,6]. Approximately 25% of patients develop amyloidosis, a condition in which the build-up of proteins can cause vital organs to fail, resulting in renal failure and requiring kidney transplantation. Approximately 20% of patients with NOMID, the most severe form of CAPS, die before reaching adulthood [2,6,10]. CAPS is believed to occur in approximately one in 2500 people in the EU [6,11], but fewer than 1000 cases have been reported worldwide because of poor diagnosis [5,6].

The CAPS filing was based on a clinical trial program involving more than 100 patients. Data from a pivotal study published in The New England Journal of Medicine show that Ilaris produced a rapid, complete and sustained response in most patients [2]. 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, p<0.001) [2]. Ilaris was generally well tolerated and there was no consistent pattern of adverse events apart from a slight increase in infections [2].

‘In CAPS studies, symptoms improved within 24 hours after patients received a single dose of Ilaris. The disease was barely detectable in the blood after two weeks and the remission of symptoms was sustained for six months,’ said Helen J. Lachmann, MD of the UK National Amyloidosis Centre at the Royal Free and University College Medical School in London, UK. ‘By effectively turning off the disease activity, Ilaris has the potential to transform patients’ lives by offering long-term control of their disease.’

Ilaris was approved in Switzerland in July 2009 to treat all three forms of CAPS in adults and children over four years old and in the US in June 2009 to treat two forms of CAPS. Priority reviews are ongoing in other countries, including Australia, Brazil and Canada.

References

1  Ilaris (canakinumab) prescribing information
2  Lachmann, H.J. et al. (2009) Use of canakinumab in the cryopyrin-associated periodic syndrome. N. Engl. J. Med. 360, 2416–2425
3  Arcalyst (rilonacept) prescribing information
4  Kineret (anakinra) prescribing information
5  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. Last accessed September 23, 2009
6  Durrant, K.L.W. et al. CAPS Cryopyrin-Associated Periodic Syndromes 2008. Available at: http://www.nomidalliance.net/Download1.html. Last accessed September 23, 2009
7  Kastner, D.L. (2005) Hereditary Periodic Fever Syndromes. Hematology 2005 – American Society of Hematology Education Program 74–81. Available at http://asheducationbook.hematologylibrary.org/cgi/reprint/2005/1/74
8  Joost, P.H. et al. (2006) The inflammasome – a linebacker of innate defense. N. Engl. J. Med. 355, 730–732
9  Lachmann, H.J. et al. (2009) In vivo regulation of interleukin 1 in patients with cryopyrin-associated periodic syndromes. J. Exp. Med. www.jem.org/cgi/doi/10.1084/jem.20082481
10  Prieur, A-M. (2003) CINCA syndrome. Orphanet. Available at: http://www.orpha.net/data/patho/Pro/en/CINCA-FRenPro3395.pdf. Last accessed September 23, 2009
11  European Medicines Agency (EMEA). Pre-authorisation evaluation of medicines for human use. Committee for orphan medicinal products. Available at http://www.emea.europa.eu/pdfs/human/comp/opnion/17086808en.pdf. Last accessed September 23, 2009