Date: 2013-05-10
Type of information: Granting of a Market Authorisation in the EU
Product name: Ilaris® - ACZ885
Compound: canakinumab
Therapeutic area: Autoimmune diseases – Inflammatory diseases - Rare diseases
Action mechanism: monoclonal antibody. Canakinumab is a fully human monoclonal antibody that neutralizes interleukin-1 beta (IL-1 beta). Excessive production of IL-1 beta is believed to play a major role in many inflammatory diseases, including gouty arthritis. The drug is already approved in more than 60 countries, including in the EU, US, Switzerland and Japan for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), a suite of rare, life-long, genetic, autoinflammatory diseases with debilitating symptoms. It is also being investigated in a number of inflammatory conditions, which include, systemic juvenile idiopathic arthritis (SJIA), Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS), Familial Mediterranean Fever (FMF) and cardiovascular disease.
Company: Novartis (Switzerland)
Disease: gouty arthritis attacks
Latest news: * On March 1, 2013, Novartis has announced that the European Commission (EC) has approved llaris® (canakinumab, ACZ885) in the treatment of patients with acute gouty arthritis who suffer frequent attacks, and whose symptoms cannot or should not be managed with current treatment options. Ilaris® is the first biologic approved in the EU for symptomatic pain relief in a gouty arthritis indication, and is administered in a single, subcutaneous injection of 150 mg. Ilaris® is specifically indicated for the 'symptomatic treatment of adult patients with frequent gouty arthritis attacks (at least 3 attacks in the previous 12 months) in whom non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine are contraindicated, are not tolerated, or do not provide an adequate response, and in whom repeated courses of corticosteroids are not appropriate.
The EC also granted an additional year of data exclusivity to Novartis based on the significant clinical benefit over existing treatments demonstrated for Ilaris.
Now that the EC has approved llaris® in this additional indication, Regeneron Pharmaceuticals will receive an additional potential royalty stream. Under a June 2009 agreement with Novartis, Regeneron receives royalties on worldwide sales of Ilaris®. The overall royalty rate in the agreement starts at 4% and reaches 15% when annual sales exceed $1.5 billion. In 2012, Regeneron reported full year Ilaris® royalties of $2.8 million.
* On January 17, 2013, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion for the use of llaris® (canakinumab, ACZ885) in the treatment of patients with acute gouty arthritis who suffer frequent attacks, and whose symptoms cannot or should not be managed with current treatment options. When approved, Ilaris® will be specifically indicated for the 'symptomatic treatment of adult patients with frequent gouty arthritis attacks (at least 3 attacks in the previous 12 months) in whom non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine are contraindicated, are not tolerated, or do not provide an adequate response, and in whom repeated courses of corticosteroids are not appropriate'.
Data from two Phase III trials and their extensions, which informed the CHMP's positive opinion for Ilaris® in gouty arthritis, showed that patients treated with Ilaris experienced significantly greater pain relief compared to the injectable steroid triamcinolone acetonide (TA). The majority of adverse events (AEs) were mild to moderate, with infections (e.g. upper respiratory tract infections and nasopharyngitis) being the most frequent of them.
Ilaris® has been assessed for the treatment of acute gouty arthritis attacks in two multicentre, randomized, double-blind, active-controlled studies in patients with frequent gouty arthritis attacks (>=3 in the previous year) who were unable to use NSAIDs or colchicine (due to contraindication, intolerance or lack of efficacy). The studies were 12 weeks in duration followed by 12 week double-blind initial extensions. A total of 454 patients were randomized to receive a single dose of Ilaris 150 mg via subcutaneous injection or TA 40 mg via intramuscular injection.Pain intensity in the overall study population was statistically significantly lower for Ilaris® 150 mg compared to TA at 72 hours (-10.7 mm, p<0.0001), with an absolute mean decrease in VAS score of approximately -50 mm. Reduction in pain was observed as early as 6 hours after dosing in both groups. A statistically significant difference between treatments was observed from 24 hours to 7 days. Ilaris also reduced the risk of subsequent attacks.
Safety results showed an increased incidence of AEs for Ilaris® compared to TA, with 66% vs. 53% of patients reporting any adverse event and 20% vs. 10% of patients reporting an infection adverse event over 24 weeks.
A sub-analysis of these studies included 101 patients unable to use NSAIDs and colchicine, and on stable ULT or unable to use ULT. Pain relief was similar to that shown in the total study population (-10.2 mm for Ilaris 150 mg compared with TA at 72 hours, p=0.0208).
In the US, Novartis continues to work with the FDA to determine the next steps for ACZ885 in gouty arthritis, following a Complete Response letter received in August 2011 with a request by the Agency for additional clinical data to evaluate the benefit risk profile in refractory patients.
* On June 21, 2011, Novartis announced that an advisory committee of the FDA voted in favor of the overall efficacy but not the overall safety of ACZ885 (canakinumab) to treat gouty arthritis attacks in patients who cannot obtain adequate relief with non-steroidal anti-inflammatory drugs (NSAIDs) or colchicine. Committee members raised the potential for use in a more narrow population of gouty arthritis patients.
Patents:
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2013-05-10
UE authorization: 2013-03-01
Favourable opinion UE: 2013-01-17
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: OTC status: Other news:
