Novartis AG's Secukinumab Set to Challenge Amgen, Pfizer Inc.'S Enbrel®

Secukinumab (AIN457) showed superiority over Enbrel® in clearing skin, according to pivotal Novartis Phase III psoriasis results at EADV

Basel, October 3, 2013 - Novartis announced today results from the head-to-head Phase III FIXTURE study showing secukinumab (AIN457), an interleukin-17A (IL-17A) inhibitor, was significantly superior to Enbrel®* (etanercept) in moderate-to-severe plaque psoriasis[1]. Enbrel is a current standard-of-care anti-TNF medication approved to treat moderate-to-severe plaque psoriasis. These new results were presented today at the 22nd Congress of the European Association of Dermatology and Venereology (EADV) in Istanbul, Turkey[1].

The pivotal FIXTURE study met all primary and pre-specified key secondary endpoints(p<0.0001 for placebo comparisons and p=0.0250 for Enbrel comparisons)[1]. Both doses of secukinumab showed improved efficacy to Enbrel throughout the 52 week study, beginning as early as Week 2 and confirmed by Week 12 when the primary endpoints were assessed[1]. Importantly, more secukinumab patients experienced almost clear skin (described as PASI 90) and completely clear skin (PASI 100) compared to Enbrel[1], which are higher standards of skin clearance compared to the standard efficacy measures used in most psoriasis clinical studies.

"These exciting data suggest that with secukinumab, we have the potential to help more patients achieve clear skin, which is the ultimate treatment goal," said David Epstein, Head of the Pharmaceuticals Division of Novartis Pharma AG.

"The data also show that specifically targeting IL-17A may offer a new and effective treatment approach for people living with moderate-to-severe plaque psoriasis."

FIXTURE compared two doses of secukinumab (300 mg and 150 mg) with Enbrel 50 mg and placebo[1]. The co-primary endpoints were assessed at Week 12 and compared secukinumab efficacy versus placebo according to the Psoriasis Area and Severity Index 75 (PASI 75) and the Investigator's Global Assessment (IGA mod 2011)[1].

The study also showed that 72% of secukinumab 300 mg patients experienced at least a 90% reduction in skin redness, thickness and scaling (PASI 90)[1] by Week 16 of the study. More than half (54%) of secukinumab 300 mg patients achieved PASI 90 as early as Week 12, compared to 21% of Enbrel patients[1]. Secukinumab 300 mg patients were also more likely to experience completely clear skin compared to those taking Enbrel in the study, as measured by PASI 100 at Week 12 (24% versus 4%)[1].

Secukinumab-treated patients also had their symptoms resolved faster than those treated with Enbrel in the study[1]. Clinically relevant differences were observed as early as Week 2, and on average secukinumab 300 mg patients had their symptoms halved by Week 3, compared to Week 8 for Enbrel patients[1].

Secukinumab efficacy was sustained over the full one year duration of the study. In FIXTURE, nearly twice as many patients treated with secukinumab 300 mg had a PASI 90 response at Week 52 compared to Enbrel (65% vs. 33%)[1].

There were no major safety signals identified in FIXTURE or the broader secukinumab Phase III clinical trial program in moderate-to-severe plaque psoriasis. In FIXTURE, the incidence of adverse events (AEs) was similar between both secukinumab treatment arms (300 mg and 150 mg), and was comparable to Enbrel[1]. The most common AEs in any treatment group (including placebo) throughout the 52 week treatment period were nasopharyngitis and headache (occurring in between 12-36 patients per 100 patient years in all groups)[1]. At the same time point, serious AEs (SAEs) were experienced by 6% of secukinumab 300 mg, 5% of secukinumab 150 mg and 6% of Enbrel patients[1]. There were no deaths reported during the study[1].

Secukinumab is the first therapy selectively targeting IL-17A to have Phase III results presented. IL-17A is a central cytokine (messenger protein) involved in the development of psoriasis, and is found in high concentrations in psoriasis skin plaques[2]-[4]. Research shows that IL-17A, in particular, plays a key role in driving the body's autoimmune response in disorders such as moderate-to-severe plaque psoriasis and is a preferred target for investigational therapies[2]-[6].

Nearly 3% of the world's population, or more than 125 million people, are affected by plaque psoriasis[7]. This is a common and debilitating disease - even those with very mild symptoms find their condition affects their everyday lives[8]. Psoriasis is also associated with psychosocial effects and those with more severe disease are at a greater risk of death from comorbid diseases such as heart disease and diabetes[9],[10].

Novartis announced top-line results from the FIXTURE study earlier this year. FIXTURE forms part of the robust secukinumab Phase III clinical trial program in moderate-to-severe plaque psoriasis that involved more than 3,300 patients in over 35 countries worldwide. Regulatory submissions of secukinumab in moderate-to-severe plaque psoriasis remain on track in the EU and US for the second half of 2013.

About FIXTURE and the secukinumab data presented at EADV

FIXTURE (the Full year Investigative eXamination of secukinumab vs. eTanercept Using 2 dosing Regimens to determine Efficacy in psoriasis) was a randomized double-blind, placebo-controlled, multicenter, global pivotal Phase III registration study involving 1,306 patients.

The co-primary endpoints were assessed at Week 12 and compared secukinumab efficacy versus placebo according to PASI 75 and IGA mod 20111. These endpoints were used also to demonstrate superiority of secukinumab vs. etanercept. Secondary measures included PASI 50, 75, 90 and 100 at different time points. In addition, the likelihood of loss of response at Week 52 was calculated by determining the proportion of patients who lost PASI 75 at Week 52, after initially achieving it at Week 12[1].

Data from an additional Phase III study of secukinumab in moderate-to-severe plaque psoriasis was also presented today at EADV[13]. The SCULPTURE (Study Comparing secukinumab Use in Long-term Psoriasis maintenance therapy: fixed regimens vs reTreatment Upon start of RElapse) trial found that patients who initially achieved PASI 75 at Week 12 were more likely to maintain their response if they received secukinumab at fixed monthly intervals, compared to treatment only on 'start of relapse'[13]. Results of two additional studies will also become available tomorrow.

About secukinumab (AIN457)

Secukinumab (AIN457) is a fully human IgG1 monoclonal antibody that selectively binds to and neutralizes IL-17A, a key pro-inflammatory cytokine[2]-[4]. 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 secukinumab may potentially provide a new mechanism of action for the successful treatment of immune-mediated diseases[14]-[18]. Phase III results from two additional Phase III studies in moderate-to-severe plaque psoriasis will be presented in 2014, and in 2014 and beyond for arthritic conditions. Phase II studies are also ongoing in other areas, including multiple sclerosis.

About Novartis in specialty dermatology

Novartis is committed to developing innovative, life-changing specialty dermatology therapies redefining treatment paradigms and transforming patient care in severe skin diseases where there are remaining high unmet medical needs. The Novartis specialty dermatology portfolio includes two unique targeted products in Phase III development, secukinumab for moderate-to-severe plaque psoriasis and omalizumab (Xolair®) for chronic spontaneous urticaria (CSU). There are also more than 10 compounds in early stage development for a wide range of severe skin diseases in the Novartis specialty dermatology portfolio.

For more information about the Novartis commitment to specialty dermatology, visit: www.skintolivein.com: http://www.skintolivein.com/.

Disclaimer

The foregoing release contains forward-looking statements that can be identified by terminology such as "on track," "suggest," "potential," "goal," "may," "investigational," "on-track," "suggested," "potentially," "will," "ongoing," "committed," or similar expressions, or by express or implied discussions regarding potential marketing submissions or approvals for secukinumab (AIN457), potential submissions or approvals for new indications or labeling for Xolair, or regarding potential future revenues from such products. 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 to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that secukinumab (AIN457) will be submitted or approved for sale in any market, or at any particular time. Nor can there be any guarantee that Xolair will be submitted or approved for any additional indications or labeling in any market. Neither can there be any guarantee that such products will achieve any particular levels of revenue in the future. In particular, management's expectations regarding these products could be affected by, among other things, unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; unexpected regulatory actions or delays or government regulation generally; 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 2012, the Group achieved net sales of USD 56.7 billion, while R&D throughout the Group amounted to approximately USD 9.3 billion (USD 9.1 billion excluding impairment and amortization charges). Novartis Group companies employ approximately 131,000 full-time-equivalent associates and operate in more than 140 countries around the world. For more information, please visit http://www.novartis.com: http://www.novartis.com/.

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*Enbrel® is a registered trademark of Amgen Inc.

References

[1] Langley R, FIXTURE oral presentation at EADV.

[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. Nat Rev Drug Discov. 2010; 9(9):703-718.

[5] Onishi RM, Gaffen SL. Interleukin-17 and its target genes: mechanisms of interleukin-17 function in disease. Immunology. 2010; 129(3):311-321.

[6] Krueger J, Fretzin S, Suárez-Fariñas M, et al. IL-17A is essential for cell activation and inflammatory gene circuits in subjects with psoriasis. J Allergy Clin Immunol. 2012; 130(1):145-154.

[7] International Federation of Psoriasis Associations (IFPA) World Psoriasis Day website. "About Psoriasis." http://www.worldpsoriasisday.com/web/page.aspx?refid=114:

http://www.worldpsoriasisday.com/web/page.aspx?refid=114. Accessed August 2013.

[8] Mason AR, Mason J, Cork M et al. Topical treatments for chronic plaque psoriasis. Cochrane Database Syst Rev. 2009;15;(2):CD005028.

[9] Abuabara K, Azfar RS, Shin DB, Neimann AL, Troxel AB, Gelfand JM. Cause-specific mortality in patients with severe psoriasis: a population-based cohort study in the U.K. Br J Dermatol. 2010 Sep;163(3):586-592

[10] Gelfand JM, Troxel AB, Lewis JD, Kurd SK, Shin DB, Wang X, Margolis DJ, Strom BL. The risk of mortality in patients with psoriasis: results from a population-based study. Arch Dermatol. 2007 Dec;143(12):1493-1499.

[11] Papp KA, Tyring S,Lahfa M, et al._A global phase III randomized controlled trial of etanercept in psoriasis: safety, efficacy, and effect of dose reduction. Br J Dermatol 2005;152:1304-1312.

[12]Leonardi CL, Powers JL, Matheson RT, et al. Etanercept as monotherapy in patients with psoriasis. NEJM 2003;349:2014-2022.

[13] SCULPTURE oral presentation at EADV.

[14] Papp KA, Langley RG, Sigurgeirsson B, et al. Efficacy and safety of secukinumab in the treatment of moderate-to-severe plaque psoriasis: a randomized, double-blind, placebo-controlled phase II dose-ranging study. BJD 2013; 168, pp412-421.

[15] Rich PA, Sigurgeirsson B, Thaci D, et al. Secukinumab induction and maintenance therapy in moderate-to-severe plaque psoriasis: a randomized, double-blind, placebo-controlled, phase II regimen-finding study. BJD 2013;168: 402-411.

[16] Genovese MC, Durez P, Richards HB, et al. Efficacy and safety of secukinumab in patients with rheumatoid arthritis: a phase II, dose-finding, double-blind, randomised, placebo controlled study. Ann Rheum Dis 2013;72:863-869.

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

[18] McInnes IB, Sieper J, Braun J, et al. Efficacy and safety of secukinumab, a fully human anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe psoriatic arthritis: a 24-week, randomised, double-blind, placebo-controlled, phase II proof-of-concept trial. Ann Rheum Dis 2013 Jan 29; doi:10.1136/annrheumdis-2012-202646.

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