Novartis receives positive CHMP opinion for Ilaris® to treat patients whose acute gouty arthritis cannot be managed with standard of care

Novartis International AG / Novartis receives positive CHMP opinion for Ilaris® to treat patients whose acute gouty arthritis cannot be managed with standard of care . Processed and transmitted by Thomson Reuters ONE. The issuer is solely responsible for the content of this announcement.

• CHMP endorsed the use of Ilaris in patients with acute gouty arthritis, who suffer frequent attacks and for whom current treatments are unsuitable or ineffective
   
• Ilaris, the only approved fully human monoclonal antibody targeting interleukin-1 beta (IL-1 beta), inhibits inflammation through sustained neutralization of IL-1 beta
   
• Current therapies do not offer relief to certain groups of gouty arthritis patients, particularly those with serious comorbidities, during their severe, crippling attacks[1],[2]

Basel, January 18, 2013 - Novartis announced today that 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.

"Novartis welcomes the decision by the CHMP in support of the approval of Ilaris in the EU," said David Epstein, Division Head of Novartis Pharmaceuticals. "When approved, lIaris will provide a new treatment option for patients who have endured frequent and crippling gouty arthritis attacks and where existing therapies do not offer relief. We look forward to receiving the final decision from the European Commission in the coming months."

Ilaris is the only available fully human monoclonal antibody that specifically targets IL-1 beta and, when approved, will offer patients suffering gouty arthritis attacks rapid pain relief via a single subcutaneous injection of 150 mg.

Gouty arthritis, commonly referred to as gout, is a serious, chronic and progressive inflammatory disease that generally affects 1 to 4% of adults[3-7]. Gouty arthritis 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[1],[2],[8],[9].

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'. Since urate lowering therapy (ULT) is generally advised in these patients, Ilaris may provide sufficient pain relief to allow initiation or continuation of ULT. 

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)[10]. 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.

The European Commission generally follows the recommendations of the CHMP and usually delivers its final decision within three months of the CHMP recommendation.

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[10].

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[10].

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[10].

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[11].

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)[12].

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[11]. 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.

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), a suite of rare, life-long, genetic, autoinflammatory diseases with debilitating symptoms[11]. Ilaris is 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. 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[7],[13]. The chronic and progressive disease is characterized by recurrent attacks in select joints[3]. These 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[3],[14]. The intense inflammatory response associated with these attacks may cause severe pain and debilitating symptoms that can last a week or more[3],[14],[15].

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[2],[11],[16]. As a result, there is a significant unmet medical need among individuals with gouty arthritis.

Disclaimer
The foregoing release contains forward-looking statements that can be identified by terminology such as "positive opinion," "endorsed," "will," "look forward to," "generally follows," "recommendation," "would," or similar expressions, or by express or implied discussions regarding potential new indications or labeling for Ilaris or regarding potential future revenues from Ilaris. You should not place undue reliance on these statements.  Such forward-looking statements reflect the current views of management regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results with Ilaris to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Ilaris will be submitted or approved for any additional indications or labeling in any market. Nor can there be any guarantee that Ilaris will achieve any particular levels of revenue in the future. In particular, management's expectations regarding Ilaris could be affected by, among other things, unexpected regulatory actions or delays or government regulation generally; unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; competition in general; government, industry and general public pricing pressures; unexpected manufacturing issues; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; the impact that the foregoing factors could have on the values attributed to the Novartis Group's assets and liabilities as recorded in the Group's consolidated balance sheet, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Novartis
Novartis provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, eye care, cost-saving generic pharmaceuticals, preventive vaccines and diagnostic tools, over-the-counter and animal health products. Novartis is the only global company with leading positions in these areas. In 2011, the Group achieved net sales of USD 58.6 billion, while approximately USD 9.6 billion (USD 9.2 billion excluding impairment and amortization charges) was invested in R&D throughout the Group. Novartis Group companies employ approximately 127,000 full-time-equivalent associates and operate in more than 140 countries around the world. For more information, please visit http://www.novartis.com.

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References
[1] Harrold LR, Yood RA, Mikuls TR, et al. Sex differences in gout epidemiology: evaluation and treatment. Ann Rheum Dis 2006; 65(10):1368-72.
[2] Riedel AA, Nelson M, Wallace K, Joseph-Ridge N, Cleary M, Fam AG. Prevalence of Comorbid Conditions and Prescription Medication Use Among Patients With Gout and Hyperuricemia in a Managed Care Setting. J Clin Rheumatol 2004; 10(6):308-14.
[3] Schumacher HR, Jr. The pathogenesis of gout. Cleve Clin J Med 2008; 75 Suppl S2-4.
[4] Badley E, DesMeules M. Arthritis in Canada: an ongoing challenge. Ottawa: Public Health Agency of Canada. 2003.
[5] Begg S, Vos T, Barker B, Stevenson C, Stanley L, Lopez AD, 2007. The burden of disease and injury in Australia 2003. PHE 82. Canberra: AIHW.
[6] Annemans l, Spaepen E, Gaskin M, et al. Gout in the UK and Germany: prevalence, comorbidities and management in general practice 2000-2005. Ann Rheum Dis. 2008; 67(7):960-6.
[7] Zhu Y, Pandya B, Choi H. Increasing gout prevalence in the US over the last two decades: The National Health and Nutrition Examination Survey (NHANES). Presented at: The American College of Rheumatology Annual Scientific Meeting, Oct, 2010, Atlanta, GA.
[8] Choi HK, Ford ES, Li C, Curhan G. Prevalence of the metabolic syndrome in patients with gout: the Third National Health and Nutrition Examination Survey. Arthritis Rheum 2007; 57(1):109-15.
[9] Becker MA, Schumacher HR, Espinoza LR, et al. The urate-lowering efficacy and safety of febuxostat in the treatment of the hyperuricemia of gout: the CONFIRMS trial. Arthritis Res Ther; 12(2):R63.
[10] Schlesinger N, Alten RE, Bardin T, et al. Canakinumab for acute gouty arthritis in patients with limited treatment options: results from two randomised, multicentre, active-controlled, double-blind trials and their initial extensions. Ann Rheum Dis 2012.
[11] Ilaris [prescribing information]. Surrey, UK: Novartis Pharmaceuticals UK Ltd; 2013.
[12] Bardin T, So A, Alten R, et al. Efficacy and safety of canakinumab vs triamcinolone acetonide in patients with gouty arthritis unable to use nonsteroidal anti-inflammatory drugs and colchicine, and on stable urate lowering therapy (ULT) or unable to use ULT. Abstract at: 2012 ACR/ARHP Annual Meeting; November 9-14; Washington, D.C., USA.
[13] Silman AJ, Pearson JE. Epidemiology and genetics of rheumatoid arthritis.  Arthritis Res. 2002;4 Suppl S265-72.
[14] Mandell BF. Clinical manifestations of hyperuricemia and gout. Cleve Clin J Med 2008; 75 Suppl S5-8.
[15] So A, De Meulemeester M, Pikhlak A, et al. Canakinumab for the treatment of acute flares in difficult-to-treat gouty arthritis: Results of a multicenter, phase II, dose-ranging study. Arthritis Rheum 2010; 62(10):3064-76.
[16] Jordan KM, Cameron JS, Snaith M, et al. British Society for Rheumatology and British Health Professionals in Rheumatology guideline for the management of gout. Rheumatology (Oxford) 2007; 46(8):1372-4.

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