BASEL, Switzerland October 28, 2009 -- The new biological medicine canakinumab (Ilaris) has been approved in the European Union to treat adults and children as young as 4 years old with cryopyrin-associated periodic syndrome (CAPS), a rare life-long auto-inflammatory disease with debilitating symptoms and few treatment options[1],[2],[3].
The accelerated EU decision follows approvals in the United States and Switzerland, where canakinumab was granted priority review in view of the significant unmet medical need. Canakinumab is the only medicine approved in the European Union for CAPS patients as young as 4 years old, and for patients with the most debilitating form of CAPS, neonatal-onset multisystem inflammatory disease (NOMID). It is a fully human monoclonal antibody given by injection under the skin once every 2 months, which is the longest dosing interval of any available treatment.
The approval of canakinumab is based on a clinical trial programme involving more than 100 patients. According to data published earlier this year in The New England Journal of Medicine, canakinumab 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. None of the patients treated with canakinumab (0 out of 15) experienced a disease flare compared to 13 of the 16 patients who received placebo (0% vs. 81% respectively, P < .001) (N Engl J Med. 2009;360:2416-2425).
"In CAPS studies, symptoms improved within 24 hours after patients received a single dose of [canakinumab]. The disease was barely detectable in the blood after 2 weeks, and the remission of symptoms was sustained for 6 months," said Helen J. Lachmann, MD, UK National Amyloidosis Centre, Royal Free and University College Medical School, London, United Kingdom. "By effectively turning off the disease activity, [canakinumab] has the potential to transform patients' lives by offering long-term control of their disease."
Canakinumab was generally well tolerated and there was no consistent pattern of adverse events apart from a slight increase in infections. Two patients experienced serious adverse events, namely a lower urinary tract infection and vertigo. The most common adverse events were nasopharyngitis, diarrhoea, influenza, headache, and nausea. Canakinumab was not associated with any severe injection-site reactions and those that did occur were classified as mild-to-moderate.
Canakinumab, previously known as ACZ885, targets and normalises the production of a protein within the immune system called interleukin-1 (IL-1) beta. In CAPS patients, IL-1 beta is overproduced causing widespread inflammation and tissue damage. Symptoms, such as debilitating fatigue, fever, joint pain and conjunctivitis, can be present from infancy and continue throughout the patient's life.
If left untreated, CAPS may have serious consequences such as deafness, bone deformities, erosive joint destruction, and central nervous system damage leading to loss of vision. Around 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.
CAPS is estimated to occur in 1 in 2,500 people in the European Union, but fewer than 1,000 cases have been reported worldwide due to poor diagnosis. CAPS includes 3 distinct auto-inflammatory disorders of increasing severity: familial cold auto-inflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and NOMID. Canakinumab is the only treatment indicated in the European Union and Switzerland to treat all 3 disorders.
Studies with ACZ885 are ongoing in other diseases in which IL-1 beta plays an important role, such as chronic obstructive pulmonary disease (COPD), type 2 diabetes, systemic juvenile idiopathic arthritis (SJIA), and gout. Not all potential patients with these diseases would be eligible for treatment with ACZ885, if approved.
The EU approval was granted under exceptional circumstances, a common practice with so-called orphan drugs. This reflects a need for additional data due to factors such as the rarity of the disease or lack of scientific knowledge. The situation is reviewed every year until the European Medicines Agency (EMEA) is able to grant a normal approval.
In addition to its orphan drug status for CAPS, canakinumab has been designated as an orphan drug for treating SJIA, the most severe form of arthritis in children, in the United States, European Union, and Switzerland, and has fast-track status for SJIA in the United States.
Canakinumab was approved in Switzerland in July 2009 to treat all 3 forms of CAPS in adults and children over 4 years old, and in the United States in June 2009 to treat 2 forms of CAPS, namely FCAS and MWS, while a study in NOMID patients is under way. Priority reviews are ongoing in other countries including Australia, Brazil and Canada.
SOURCE: Novartis
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