Novartis Advances Head-to-Head Superiority Trials of Cosentyx Versus Humira And Proposed Biosimilar Adalimumab

• SURPASS is the first head-to-head superiority trial versus proposed biosimilar adalimumab** in ankylosing spondylitis (AS)[1]
  
• EXCEED is the first head-to-head superiority trial versus Humira^®* in psoriatic arthritis (PsA)[2]
• Cosentyx is a targeted biologic inhibiting IL-17A, cornerstone cytokine involved in the inflammation of entheses[3]

Basel, January 9, 2018 - Novartis announced today the initiation of SURPASS, a head-to-head clinical trial of Cosentyx^® (secukinumab) versus proposed biosimilar adalimumab** in ankylosing spondylitis (AS). SURPASS is the first head-to-head clinical trial in AS investigating superiority of Cosentyx in slowing spinal bone damage versus proposed biosimilar adalimumab**. SURPASS is currently recruiting patients, with the ‘first patient first visit’ already achieved in November 2017.[1]

SURPASS and EXCEED are part of a larger rheumatology program for Cosentyx. EXCEED is a head-to-head clinical trial of Cosentyx versus Humira^®* (adalimumab) in psoriatic arthritis (PsA), which is already recruiting. EXCEED is the first large double-blinded head-to-head clinical trial versus Humira^®* in PsA investigating superiority of Cosentyx on ACR 20 at 52 weeks as the primary endpoint.[2]

“The EXCEED and SURPASS head-to-head trials are addressing important clinical questions solving residual uncertainty for patients with PsA and AS,” said Dr. Robert Landewé, Professor of Rheumatology in the Amsterdam Rheumatology and Clinical Immunology Center & the Zuyderland Medical Center, Heerlen, the Netherlands. “Head-to-head trials deliver the most robust data helping to advance clinical practice and are key to clinical decision making. In this case, these data would add to the body of evidence to underline the benefit of different biologic pathways for physicians.”

“Cosentyx is backed by strong clinical efficacy and safety data and already has supported more than 125,000 patients worldwide,” said Vas Narasimhan, Global Head, Drug Development and Chief Medical Officer, Novartis. “Many patients living with PsA and AS cannot enjoy a normal life as they are experiencing persistent pain and fatigue, and are at risk of long-term mobility loss. These patients deserve the best treatment possible and we are hopeful that the EXCEED and SURPASS trials will provide valuable answers for doctors and patients in their decision making.”

Cosentyx is the first targeted biologic that specifically inhibits IL-17A, cornerstone cytokine involved in the inflammation of entheses in spondyloarthritis, which plays a major role in PsA and AS[3]-[6]. Both conditions are debilitating autoimmune diseases with a high risk of mobility loss. Approximately 40 percent of PsA patients will develop irreversible joint damage and permanent physical deformity[7]. For AS patients, inflammation of the sacroiliac joints and new bone formation of the spine is associated with increased levels of IL-17A, with severe cases progressing to irreversible spinal fusion[8].

Cosentyx is the first and only fully human IL-17A inhibitor approved to treat AS, PsA and psoriasis[4]. It has demonstrated rapid and sustained efficacy as well as a consistently favorable safety profile, including injection site pain at rates similar to placebo[9]-[15]. To date, Cosentyx has been used by more than 125,000 patients worldwide[9].

About Cosentyx and IL-17A
Cosentyx (secukinumab) is the first and only fully-human IL-17A inhibitor approved to treat ankylosing spondylitis (AS), psoriatic arthritis (PsA) and psoriasis[4]. Cosentyx is a targeted treatment that specifically inhibits IL-17A, cornerstone cytokine which plays a significant role in the pathogenesis of AS, PsA and psoriasis[3]-[6]. Cosentyx is approved in more than 70 countries for the treatment of active AS and PsA, which includes the European Union countries and the US, as well as Japan[16].

Cosentyx is also approved in more than 80 countries for the treatment of moderate-to-severe plaque psoriasis, which includes the European Union countries, Japan, Switzerland, Australia, the US and Canada. In Europe, Cosentyx is approved for the first-line systemic treatment of moderate-to-severe plaque psoriasis in adult patients[4]. In the US, Cosentyx is approved as a treatment for moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy (light therapy)[17].

About SURPASS head-to-head clinical trial[1]
Novartis has initiated SURPASS, the first ever head-to-head superiority clinical trial of Cosentyx versus proposed biosimilar adalimumab** in slowing spinal bone damage as the primary endpoint in AS. Effect on progressive structural damage of the spine is one of the important attributes clinicians look for when assessing the performance of AS treatment options. SURPASS will allow clinicians and patients to make better treatment decisions by evaluating this important attribute of AS therapy, reducing the progression of spinal structural damage.

SURPASS will be the largest randomized, controlled study of a biologic treatment in AS and is a 1 year, parallel-group study with three treatment arms: Cosentyx 150 mg subcutaneously (sc); Cosentyx 300 mg sc and proposed biosimilar adalimumab** 40 mg sc in patients with active AS. The primary endpoint is the proportion of patients with no spinal radiographic structural progression, defined as a change from baseline of =<0.5 in mSASSS, at 2 years. Key secondary endpoints are mean change in mSASSS, new syndesmophyte formation, and MRI measures of inflammation, at 2 years.

About EXCEED head-to-head clinical trial[2]
Novartis has initiated EXCEED, the first ever large double-blinded head-to-head clinical trial evaluating Humira^®* (adalimumab) versus Cosentyx. EXCEED is a 1 year, multi-center, randomized, double-blind, active control, Phase IIIb study evaluating the efficacy of Cosentyx monotherapy compared with Humira* monotherapy in patients with active PsA who are naïve to biologic therapy. The study will include a large patient population involving over 800 biologic-naïve patients with PsA.

The primary endpoint will assess statistical superiority of Cosentyx monotherapy against adalimumab monotherapy for ACR 20 response rates at 1 year. Other secondary endpoints, all at 52 weeks, include PASI 90, ACR 50, disability index (HAQ-DI score) relative to baseline, and resolution of enthesitis.

About ankylosing spondylitis and psoriatic arthritis
AS is part of a family of life-long inflammatory diseases, which also includes PsA. AS is characterized by inflammation of the sacroiliac joints and new bone formation in the spine caused by increased levels of IL-17A, with severe cases progressing to irreversible spinal fusion[3],[8]. AS can cause serious impairment of movement in the spine and physical function, which impacts quality of life. People in their twenties and thirties, particularly males, are affected most often[18],[19].

PsA is a debilitating autoimmune disease with a high risk of mobility loss. Symptoms of PsA include joint pain and stiffness, skin and nail psoriasis, swollen toes and fingers, persistent painful swelling of the tendons, and irreversible joint damage[20]. Up to 40 percent of people can suffer from joint destruction and permanent physical deformity[7].

IL-17A plays a significant role in disease pathogenesis of AS, PsA and plaque psoriasis. Up to 30 percent of psoriasis patients will develop PsA during their lifetime, and as many as 1 in 4 people with psoriasis may have undiagnosed PsA[20],[21].

Disclaimer
This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as “potential,” “can,” “will,” “plan,” “expect,” “anticipate,” “look forward,” “believe,” “committed,” “investigational,” “pipeline,” “launch,” or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures; general economic and industry conditions, including the effects of the persistently weak economic and financial environment in many countries; safety, quality or manufacturing issues, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. 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, cost-saving generic and biosimilar pharmaceuticals and eye care. Novartis has leading positions globally in each of these areas. In 2016, the Group achieved net sales of USD 48.5 billion, while R&D throughout the Group amounted to approximately USD 9.0 billion. Novartis Group companies employ approximately 121,000 full-time-equivalent associates. Novartis products are sold in approximately 155 countries around the world. For more information, please visit http://www.novartis.com.

Novartis is on Twitter. Sign up to follow @Novartis at http://twitter.com/novartis
For Novartis multimedia content, please visit www.novartis.com/news/media-library
For questions about the site or required registration, please contact media.relations@novartis.com

* Humira is a registered trademark of AbbVie Inc.
** The proposed biosimilar adalimumab used in the SURPASS trial is a development compound from Sandoz, which is currently under review by the European Medicines Agency for the treatment of several immunological diseases.

References
[1] Effect of Secukinumab on Radiographic Progression in Ankylosing Spondylitis as compared to GP2017 (Adalimumab Biosimilar) (SURPASS). Available at: https://www.clinicaltrials.gov/ct2/show/NCT03259074. Last accessed November 2017.
[2] Efficacy of Secukinumab Compared to Adalimumab in Patients With Psoriatic Arthritis (EXCEED 1). Available at: https://clinicaltrials.gov/ct2/show/NCT02745080. Last accessed November 2017.
[3] Smith JA et al. Review: The Interleukin 23/Interleukin 17 Axis in Spondyloarthritis Pathogenesis: Th17 and Beyond. Arthritis Rheumatol. 2014;66:231-41.
[4] EU Cosentyx Summary of Product Characteristics. Novartis Europharm Limited. Available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/003729/human_med_001832.jsp&mid=WC0b01ac058001d124. Last accessed November 2017.
[5] Nestle FO et al. Mechanisms of disease psoriasis. N Eng J Med. 2009;361:496-509.
[6] Girolomoni G et al. Psoriasis: rationale for targeting interleukin-17. Br J Dermatol. 2012;167:717-24.
[7] Anwar AH, Diamond H. Psoriatic arthritis: practice essentials, background, pathophysiology and etiology. Medscape reference website. Available at: http://emedicine.medscape.com/article/2196539-overview#a6. Last accessed November 2017.
[8] Sieper J et al. Ankylosing spondylitis: an overview. Ann Rheum Dis. 2002;61(Suppl III):iii8-iii18.
[9] Novartis, data on file.
[10] Braun J et al. Secukinumab demonstrates low radiographic progression and sustained efficacy through 4 years in patients with active ankylosing spondylitis. Late breaking abstract presented at the 2017 ACR/ARHP Annual Meeting, San Diego, USA. 7^th November 2017.
[11] Bissonnette R et al. Secukinumab demonstrates high sustained efficacy and a favorable safety profile through 5 years of treatment in moderate to severe psoriasis. Presented as eposter P2223 at 26th EADV Congress 2017. 13th September 2017.
[12] Mease PJ et al. Secukinumab Provides Sustained Improvements in the Signs and Symptoms of Active Psoriatic Arthritis through 3 Years: Efficacy and Safety Results from a Phase 3 Trial. AnnRheum Dis. 2017;76:952-953.
[13] Baeten D et al. Secukinumab, interleukin-17A inhibition in ankylosing spondylitis. N Engl J Med. 2015; 373:2534-48.
[14] McInnes IB et al. Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015; 386(9999):1137-1146.
[15] Reich K et al. Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, exhibits minimal immunogenicity in patients with moderate-to-severe plaque psoriasis. Br. J. Dermatol. 2017;176:752-58.
[16] Pharmaceuticals and Medical Devices Agency. Review Report. Available at: http://www.pmda.go.jp/files/000216877.pdf. Last accessed November 2017.
[17] US Cosentyx (secukinumab) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp, 2016.
[18] Dean LE et al. Global prevalence of ankylosing spondylitis. Rheumatology (Oxford). 2014;53(4):650-7.
[19] American College of Rheumatology (ACR) website. Spondyloarthritis. Available at: http://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Spondyloarthritis. Last accessed November 2017.
[20] Mease PJ et al. Managing patients with psoriatic disease: the diagnosis and pharmacologic treatment of psoriatic arthritis in patients with psoriasis. Drugs. 2014;74:423-41.
[21] National Psoriasis Foundation. Could You Have Psoriatic Arthritis? Know the Signs. Available at https://www.psoriasis.org/psoriatic-arthritis/know-the-signs. Last accessed November 2017.

# # #

Novartis Media Relations
Central media line: +41 61 324 2200
E-mail: media.relations@novartis.com

Novartis Investor Relations
Central investor relations line: +41 61 324 7944
E-mail: investor.relations@novartis.com