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Novartis Data Show AIN457 Significantly Reduced Signs And Symptoms In Patients With Hard-To-Treat Moderate-To-Severe Plaque Psoriasis

Novartis has announced new Phase II data showing AIN457 (secukinumab) may significantly improve moderate-to-severe plaque on the , feet and nails when used every week for the first month of treatment, compared to placebo1,7. Additional analysis on patients with moderate-to-severe plaque also showed that AIN457 may successfully improve quality of life by Week 12 in the study8.

“These new AIN457 data are particularly welcome since they demonstrate significant improvement in the signs and symptoms of patients, even when difficult-to-treat areas are involved,” said Prof. , one of the study investigators and Professor of Dermatology, Venereology, and Allergology in Hamburg, Germany. “Many patients with hand, foot or nail psoriasis are restricted in their daily life and work because they may not be able to walk or use their hands, negatively impacting their quality of life.”

The results were presented at the European Academy of Dermatology and Venereology () 21st Congress, in , Czech Republic. They provide additional insight into the safety and efficacy of AIN457, following the presentation of the study’s primary endpoint at in 2011.

The new data from the sub-analyses undertaken on the Phase II study show AIN457 was nearly three times more effective than placebo at reducing moderate-to-severe on the hands and/or feet when given every week during the first month of treatment (54.3% of patients vs. 19.2% respectively, p=0.005), as measured by the Investigator’s Global Assessment (IGA)1. Patients also benefited if they received AIN457 once every four weeks, with 39.0% experiencing either “clear” or “minimal” psoriasis after 12 weeks of treatment1. Another analysis found that these AIN457 treatment schedules also notably reduced the signs and symptoms of finger nail psoriasis compared to placebo7.

The study safety analysis of these data showed a comparable safety profile between treatment and placebo, with the most common adverse events (AEs) observed being infections1,7.

Other new data presented at EADV in the total moderate-to-severe plaque psoriasis study population show that AIN457 improved skin-related quality of life in 25 times more patients after 12 weeks of treatment when given every week for the first month, compared to placebo (40.8% vs. 1.6%, p<0.001), as measured by the Dermatology Life Quality Index (DLQI)8. In this same treatment group, significantly more patients experienced improvements in pain and discomfort compared to placebo (36.2% vs. – 1.5%) from baseline; and in anxiety and depression versus placebo (16.3% vs. 6.2%), as measured by EuroQol (EQ-5D)8. The effect of psoriasis on patients’ health-related quality of life has been shown to be similar to diseases such as cancer, heart attack, arthritis, type 2 diabetes and depression9.

“These encouraging results show that through its novel mode of action, AIN457 may significantly increase treatment success and improve the quality of life of patients suffering from moderate-to-severe plaque psoriasis,” said John Hohneker, Head of Development for Integrated Hospital Care for the Pharmaceuticals Division of Novartis. “We look forward to receiving the results of the larger-scale and longer-term Phase III studies, which are expected in 2013.”

All core pivotal trials for AIN457 in moderate-to-severe plaque psoriasis are on track, involving more than 3,000 patients worldwide, and indicating a high interest from both medical and patient communities. Phase III data in moderate-to-severe plaque psoriasis is expected in 2013, with regulatory submissions to follow shortly thereafter.

About the study

Data are based on a double-blind, parallel group, placebo-controlled Phase II study involving 404 patients, which met its primary endpoint of PASI 75 (Psoriasis Area and Severity Index) responses at Week 1210. It was designed to evaluate the safety and efficacy of AIN457 in different regimens (weekly for the first month; once every four weeks; or single dose) of 150 mg given subcutaneously10.

The undertaken sub-analyses included assessment of AIN457 treatment efficacy in 131 patients with hand and/or foot psoriasis, often described as palmoplantar psoriasis1. All 404 patients were involved in assessing health-related quality of life, and data from 304 patients were used to assess AIN457 treatment efficacy in nail psoriasis7,8.

About AIN457

AIN457 is a fully human monoclonal antibody inhibiting interleukin-17A (IL-17A), a key pro-inflammatory cytokine. Proof-of-concept and Phase II studies in moderate-to-severe plaque psoriasis and arthritic conditions (psoriatic arthritis, ankylosing spondylitis and rheumatoid arthritis) have suggested that AIN457 may provide a new mechanism of action for the treatment of immune-mediated diseases10-13. The Phase III programs for these potential indications are ongoing, and first interpretable results are expected in 2013 for moderate-to-severe plaque psoriasis and in 2014 for arthritic conditions. Phase II studies are also ongoing in other areas, including multiple sclerosis.

About psoriasis

Approximately 2% of the world’s population, or around 125 million patients, are affected by plaque psoriasis, a chronic disease characterized by thick and extensive skin lesions, called plaques, known to cause itching, scaling and pain14,15. More than one third of patients with plaque psoriasis suffer from its moderate-to-severe form16.

Patients with hand, foot and nail psoriasis endure significantly greater physical disabilities than those whose psoriasis is limited to other parts of the body5,6. This includes functional disability, burning sensations, skin soreness, prolonged duration of psoriasis and the risk of joint involvement and secondary infections5,6. Estimated to affect between 10% and 55% of all psoriasis patients, nail, hand and foot psoriasis is notoriously difficult to treat and often requires systemic treatment such as biologics to maintain an adequate clinical response5,6,17.

Source

1. Paul C, Mroweitz U, Nakayama J et al. Secukinumab, a fully human, anti-interleukin (IL)-17Amonoclonal antibody improves signs and symptoms of hand and foot psoriasis: results from a phase IIregimen-finding trial. Presented at: 21st Congress of the European Academy of Dermatology andVenereology; 27-30 September, 2012; Prague, Czech Republic. Poster PRA12-0816.

2. Gaffen SL. Structure and signaling in the IL-17 receptor family. Nat Rev Immunol. 2009;9(8):556-67.

3. Ivanov S, Linden A. Interleukin-17 as a drug target in human disease. Trends Pharmacol Sci.2009;30(2):95-103.

4. Kopf M, Bachmann MF, Marsland BJ. Averting inflammation by targeting the cytokine environment. NatRev Drug Discov. 2010;9(9):703-18.

5. Radtke MA, Langenbruch AK, Schafer I et al. Nail psoriasis as a severity indicator: results from thePsoReal study. Patient Relat Outcome Meas. 2011;2:1-6

6. Pettey AA, Balkrishnan R, Rapp et al. Patients with palmoplantar psoriasis have more physical disabilityand discomfort than patients with other forms of psoriasis: implications for clinical practice. J Am AcadDermatol. 2003;49(2) :271-275.

7. Gottlieb AB, Reich K, Philipp S et al. Secukinumab improves signs and symptoms of nail psoriasis:results from a phase II regimen-finding trial. Presented at: 21st Congress of the European Academy ofDermatology and Venereology; 27-30 September, 2012; Prague, Czech Republic. Poster PRA12-0668.

8. Wilsmann-Theis D, Terui T, Draelos Z et al. Improvement with secukinumab on patient reported skinrelated quality of life (QoL) and health status among moderate-to-severe plaque psoriasis patients:results from a phase II regimen-finding trial. Presented at: 21st Congress of the European Academy ofDermatology and Venereology; 27-30 September, 2012; Prague, Czech Republic. Poster: PRA12-0822.

9. Rapp SR, Feldman SR, Exum, ML et al. Psoriasis causes as much disability as other major medicaldiseases. J Am Acad Dermatol. 1999;41(3):401-407.Leipe J, Grunke M, Dechant C et al. Role of Th17cells in human autoimmune arthritis. Arthritis Rheum. 2010;62:2876-2885.

10. Rich P.A. et al. Secukinumab, a new fully human monoclonal anti-Interleukin-17A antibody, in thetreatment of moderate-to-severe plaque psoriasis: Interim efficacy and safety data from a phase IIregimen-finding trial. Presented at: 20th Congress of the European Academy of Dermatology andVenereology; 20-24 October, 2011; Lisbon, Portugal. Oral presentation FC01.6.

11. Genovese M, Kellner H, Durez P, et al. Secukinumab treatment improves ACR50, HAQ-DI and EULARremission rates in patients with rheumatoid arthritis. At: EULAR 2012, The Annual European Congressof Rheumatology; 6-9 June 2012, Berlin, Germany. Abstract 2925.

12. Baeten D, Sieper J, Emery P, et al. The anti-il17a monoclonal antibody secukinumab (AIN457) showedgood safety and efficacy in the treatment of active ankylosing spondylitis. At: EULAR 2011, The AnnualEuropean Congress of Rheumatology, 25-28 May 2011, London, UK. Abstract 0174.

13. McInnes I, Sieper J, Braun J, et al. Anti-Interleukin 17A monoclonal antibody secukinumab reducessigns and symptoms of psoriatic arthritis in a 24-week multicenter, double-blind, randomized, placebo-controlled trial. Presented at: Annual Scientific Meeting of the American College ofRheumatology/Association of Rheumatology Health Professionals; 4-9 November 2011; Chicago, IL.Abstract 19541.

14. Raychaudhuri SP, Farber EM. The prevalence of psoriasis in the world. J Eur Acad Dermatol Venereol.2001;15:16–17.

15. Nestle FO, Kaplan DH, Barker J. Psoriasis. N Engl J Med 2009;361:496-509.

16. Herrier R. Advances in the treatment of moderate-to-severe plaque psoriasis. Am J Health-Syst Pharm2011;68:795-806.

17. Farley E, Masrour S, McKey J et al. Palmoplantar psoriasis: a phenotypical and clinical review withintroduction of a new quality-of-life assessment tool. J Am Acad Dermatol. 2009;60(6):1024-1031.

Disclaimer

The foregoing release contains forward-looking statements that can be identified byterminology such as “promising,” “on track,” “expected,” “encouraging,” “may,” “lookforward to,” “to follow,” or similar expressions, or by express or implied discussionsregarding potential marketing submissions or approvals for AIN457, or the timing of anysuch submissions or approvals, or regarding potential future revenues from AIN457. Youshould not place undue reliance on these statements. Such forward-looking statementsreflect the current views of management regarding future events, and involve known andunknown risks, uncertainties and other factors that may cause actual results with AIN457to be materially different from any future results, performance or achievementsexpressed or implied by such statements. There can be no guarantee that AIN457 will besubmitted or approved for approval in any market, or at any particular time. Nor can therebe any guarantee that AIN457 will achieve any particular levels of revenue in the future.In particular, management’s expectations regarding AIN457 could be affected by, amongother things, unexpected clinical trial results, including unexpected new clinical data andunexpected additional analysis of existing clinical data; unexpected regulatory actions ordelays or government regulation generally; competition in general; government, industryand general public pricing pressures; the company’s ability to obtain or maintain patent orother proprietary intellectual property protection; unexpected manufacturing issues; theimpact that the foregoing factors could have on the values attributed to the NovartisGroup’s assets and liabilities as recorded in the Group’s consolidated balance sheet, andother risks and factors referred to in Novartis AG’s current Form 20-F on file with the USSecurities and Exchange Commission. Should one or more of these risks or uncertaintiesmaterialize, or should underlying assumptions prove incorrect, actual results may varymaterially from those anticipated, believed, estimated or expected. Novartis is providingthe information in this press release as of this date and does not undertake anyobligation to update any forward-looking statements contained in this press release as aresult of new information, future events or otherwise.