Novartis receives EU approval for Ilaris®

Novartis announced today 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[1].

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'[1].

The EC also granted an additional year of data exclusivity to Novartis based on the significant clinical benefit over existing treatments demonstrated for Ilaris.

“The approval of Ilaris for acute gouty arthritis attacks in patients without appropriate treatment options provides new hope for those debilitated by this excruciating condition,” said David Epstein, Division Head of Novartis Pharmaceuticals. “Ilaris targets interleukin-1 beta, a key player in gouty arthritis inflammation. Our vision is to realize the potential of Ilaris wherever IL-1 beta plays a key role and available treatment options don’t give patients the help they need.”

Gouty arthritis, commonly referred to as gout, is a serious, chronic and progressive inflammatory disease that generally affects 1 to 4% of adults[2],[7]-[10]. Gouty arthritis attacks occur when the body has a strong inflammatory response to uric acid crystals forming in the affected joint, typically of the toe, foot, ankle, or knee[2],[4]. The disease is associated with a high prevalence of comorbidities, such as hypertension, kidney disease, diabetes, dyslipidemia and cardiovascular disease. These conditions can lead to contraindications for existing therapies and complications for disease management[5],[6],[11],[12].

Data from two Phase III trials and their extensions, which supported the EU approval for Ilaris in acute gouty arthritis attacks, showed that patients treated with Ilaris experienced significantly greater pain relief compared to the injectable steroid triamcinolone acetonide (TA)[13]. 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.

About Ilaris Phase III Studies

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[13].

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[13].

Both trials used an internationally recognized pain scale (visual analogue scale, or VAS) to measure differences in pain 72 hours after treatment. 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[13].

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[1].

A sub-analysis of these studies included 101 patients unable to use NSAIDs and colchicine, and on stable urate lowering therapy (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)[14].

About Ilaris

Ilaris is a selective, fully human, monoclonal antibody that inhibits IL-1 beta, which is an important part of the body’s immune system defenses[1]. Excessive production of IL-1 beta plays a prominent role in certain inflammatory diseases. Ilaris works by neutralizing IL-1 beta for a sustained period of time, therefore inhibiting inflammation.

In addition to its approval in refractory gouty arthritis in the EU, Ilaris is approved in more than 60 countries, including in the EU, US, Switzerland and Japan for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS). CAPS is a suite of rare, life-long, genetic, autoinflammatory diseases with debilitating symptoms[1]. The approved indication may vary depending upon the individual country.

Ilaris is being investigated in a number of rare inflammatory conditions, which include, systemic juvenile idiopathic arthritis (SJIA), Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS), colchicine-resistant Familial Mediterranean Fever (FMF) and cardiovascular disease. Not all patients with these diseases would be eligible for treatment with Ilaris, if approved for the applicable disease.

In the US, Novartis continues to work with the Food and Drug Administration (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.

About Gouty Arthritis

Gouty arthritis is the most common form of inflammatory arthritis in adults[10],[15]. This chronic and progressive disease is characterized by recurrent attacks in select joints[2]. The intense inflammatory response associated with these attacks may cause severe pain and debilitating symptoms that can last a week or more[2]-[4].

Treatments currently available to manage the pain and inflammation of gouty arthritis attacks, such as NSAIDs, colchicine or corticosteroids, may be inadequate or inappropriate in patients who have certain coexisting medical problems[1],[6],[16]. As a result, there is a significant unmet medical need among individuals with gouty arthritis.

References

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