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Published on 18 June 2010

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New Phase II study reveals positive results for Novartis ACZ885

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New phase II data demonstrate that the human monoclonal antibody ACZ885 (also known as canakinumab) provided highly statistically significant risk reduction of acute flares in gout patients initiating uric acid lowering therapy (UALT) compared to the anti-inflammatory standard of care (colchicine).

In this six month Phase II study, canakinumab significantly reduced the rate of flares by 48% to 75% compared to colchicine (p≤0.05). Similarly, canakinumab reduced the risk of developing at least one flare by 61% to 80% vs. colchicine p (p≤0.05). Preliminary results were presented today at the annual European League Against Rheumatism (EULAR) meeting in Rome, Italy.

“Gout patients frequently experience painful flares with debilitating consequences on their quality of life because current treatment strategies are not well tolerated and have limited efficacy[5],” said Trevor Mundel, MD, Head of Global Development at Novartis Pharma AG. “These new results reinforce previous positive data suggesting that canakinumab, if approved, can more effectively address the unmet needs of patients to both treat and prevent acute gout flares.”

Gout is one of the most painful forms of arthritis and affects at least 1% of adults in Western countries. It is caused by the accumulation in joints and surrounding tissues of uric acid crystals[8] that trigger the overproduction of interleukin-1β (IL-1β). IL-1β activates the inflammatory process leading to excruciating pain and debilitating consequences such as joint erosion and destruction.

Uric acid lowering therapy, while helping to reduce uric acid levels in the blood, does not address patient inflammation and pain. In addition, at the start of therapy, UALTs actually increase the risk of painful gout attacks due to an initial peak of uric acid. To prevent these side effects, the prophylactic use of anti-inflammatory drugs is recommended.

“Standard anti-inflammatory therapies are commonly used to reduce the inflammation and pain of acute gout flares but it is recognized that they are not always effective. Gout patients also have comorbidities making it more difficult for them to find an appropriate treatment,” said Dr Naomi Schlesinger, Department of Medicine, University of Medicine and Dentistry of New Jersey, US. “These promising data indicate that the blockade of IL-1β provided by canakinumab was effective in preventing acute flares for a sustained period of time compared to anti-inflammatory standard of care and may represent a future novel advance in the treatment of debilitating gout attacks.”

These new findings reinforce data from another Phase II study that involved patients with acute gout attacks who are intolerant, contraindicated or not responsive to common anti-inflammatory therapies. Data from this study showed that canakinumab provided better pain relief and reduced risk of acute flares by 94% versus a potent injectable corticosteroid (triamcinolone acetonide). Canakinumab is in Phase III development for the treatment and prevention of acute gout attacks and submission is planned later this year in the EU and US.

The Phase II data presented today at EULAR is a 24-week, multi-center, double-blind study and involved 432 gout patients ranging from 20 to 70 years in age who were initiating UALT (allopurinol). The study explored a number of doses of canakinumab versus colchicine and the primary endpoint sought to determine the dose of canakinumab that provides the same efficacy to the dose of the anti-inflammatory colchicine (0.5 mg) with respect to the mean number of gout flares experienced by patients during 16 weeks. All canakinumab tested doses were better than colchicine. Secondary endpoints included among others the number of patients with flares after 16 weeks and safety assessment at 24 weeks.

Canakinumab was generally well tolerated with similar incidence of adverse events across all treatment groups. The most frequent adverse events in all treatment groups were headache, arthralgia and hypertension. Infections (predominantly upper respiratory tract infection and nasopharyngitis) were slightly more frequent in the canakinumab groups (15.1% to 20.4%) than in the colchicine group (12.0%).

Under the brand name Ilaris, canakinumab is approved in the EU, US, Brazil, Canada, Australia and Switzerland for the treatment of adults and children as young as four with cryopyrin-associated periodic syndrome (CAPS), a rare life-long auto-inflammatory disease. Due to a genetic mutation in CAPS patients, IL-1β is overproduced causing widespread inflammation and tissue damage that can lead to debilitating symptoms and life-threatening complications if left untreated.

Studies are also ongoing in other diseases in which IL-1β is believed to play an important role in driving inflammation, such as systemic juvenile idiopathic arthritis (SJIA), chronic obstructive pulmonary disease (COPD) and type 2 diabetes. Not all potential patients with these diseases would be eligible for treatment with ACZ885, if approved.

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