Novartis announces NEJM publication of two major trials showing significant efficacy of Cosentyx in ankylosing spondylitis patients

• Cosentyx (secukinumab) is the first IL-17A inhibitor approved in Europe to treat ankylosing spondylitis (AS) and first treatment advance in 16 years since anti-tumor necrosis factor (anti-TNF) therapy, the current standard of care[1]
   
• Cosentyx provided improvements in the signs and symptoms, physical function and quality of life measures in active AS as early as Week 1 and through to Week 52[2]
  
  
• The study enrolled anti-TNF naïve patients and patients who had previously failed anti-TNF therapy, with clinical benefits demonstrated across the trial population[2]

             
Basel, December 23, 2015 - Novartis announced today that the results of the MEASURE 1 and MEASURE 2 Phase III studies for Cosentyx® (secukinumab) in ankylosing spondylitis (AS) were published in the New England Journal of Medicine (NEJM). These pivotal studies demonstrated significant clinical improvements with Cosentyx versus placebo in the signs and symptoms of active AS - a long-term, painful and debilitating inflammation of the spine[2],[3]. Collectively the studies form the largest clinical trial program ever conducted in AS, involving 590 patients[2].

In both studies, the primary endpoint was the proportion of patients with at least 20% improvement in Assessment of Spondyloarthritis International Society (ASAS 20) response criteria at week 16 with Cosentyx 150 mg. ASAS 20 response rates with Cosentyx 150 mg vs placebo at Week 16 were 60.8% (vs 28.7%, p<0.001) for MEASURE 1 and 61.1% (vs 28.4%, p<0.001) for MEASURE 2[2]. The studies enrolled anti-tumor necrosis factor (anti-TNF) naïve patients and patients who had previously failed anti-TNF therapy, with clinical benefits demonstrated across the trial populations[2].

Clinical improvements were seen as early as Week 1 and were sustained throughout the studies, with up to 77% of patients achieving an ASAS 20 response at the end of Week 52[2]. Efficacy assessments, except those at Week 16, were exploratory endpoints[2].

"Ankylosing spondylitis is a debilitating disease and many patients do not achieve a sufficient and sustained response from current therapies," said Vasant Narasimhan, Global Head of Development, Novartis Pharmaceuticals. "These two studies demonstrate the potential of Cosentyx to address this significant unmet need and we look forward to continuing to generate longer term data on the effect of IL-17A inhibition on ankylosing spondylitis."

Cosentyx is the first IL-17A inhibitor to demonstrate efficacy in Phase III AS studies and was recently approved in Europe to treat active AS in adults who have responded inadequately to conventional therapy, such as non-steroidal anti-inflammatory drugs (NSAIDs). New treatment options are needed for patients who do not achieve an adequate response to NSAIDs or anti-TNFs, with up to 40% of patients not responding sufficiently to the latter[4].

Cosentyx was well tolerated in both studies, with an overall safety profile consistent to that reported in clinical trials across multiple indications involving more than 9,600 patients, as well as over 12,500 patients who have already been treated in the post-marketing setting[2],[5]. The most common adverse events (AEs) seen at Week 16 were upper respiratory tract infection, headache and dyslipidemia (abnormal cholesterol / triglyceride levels)[2].

About the MEASURE 1 and MEASURE 2 studies
MEASURE 1 and MEASURE 2 are ongoing, multi-center, randomized, placebo-controlled Phase III studies to evaluate the efficacy and safety of Cosentyx in radiographic-confirmed AS compared to placebo. Both MEASURE 1 and MEASURE 2 evaluated Cosentyx 75 mg and 150 mg vs placebo. In the MEASURE 1 study patients received an intravenous loading dose of 10 mg / kg every two weeks for the first four weeks of treatment, followed by monthly subcutaneous doses that aimed to provide high exposure for induction of response. MEASURE 2 evaluated subcutaneous loading regimens.

Secondary endpoints assessed signs and symptoms, physical function and quality of life measures at Week 16 for both studies including: ASAS 40 response; change from baseline in high-sensitivity C-reactive protein (hsCRP); ASAS 5/6 improvement; changes from baseline in total BASDAI score, Medical Outcomes Study Short Form-36 Health Survey physical component summary score (SF-36 PCS), and Ankylosing Spondylitis Quality of Life score (ASQoL); ASAS partial remission and overall safety and tolerability.

• MEASURE 1: primary and all secondary endpoints were met with both Cosentyx groups in the MEASURE 1 study[2].
• MEASURE 2: primary and all secondary endpoints except ASAS partial remission were met with Cosentyx 150 mg subcutaneous in the MEASURE 2 study[2].
  • Cosentyx 75 mg did not achieve statistical significance vs placebo for primary and any of the secondary endpoints[2].

Efficacy assessments except those at Week 16 were exploratory endpoints[1].

About ankylosing spondylitis (AS)
AS is a painful, progressively debilitating condition caused by inflammation of the spine. Up to 70% of patients with severe AS develop spinal fusion (where new bone growth immobilizes the spine) over 10 to 15 years, which significantly reduces mobility and quality of life[6]. AS occurs in approximately 2 million people in the United States and Europe[7],[8],[9] and typically affects young men and women aged 25 or older[10].

About Cosentyx and interleukin-17A (IL-17A)
Cosentyx is a fully human monoclonal antibody that selectively neutralizes circulating IL-17A[11]. Cosentyx is the first IL-17A inhibitor with positive Phase III results for the treatment of psoriatic arthritis (PsA) and AS. Research suggests that IL-17A may play an important role in driving the body's immune response in psoriasis, PsA and AS[12].

Over 50 countries have also approved Cosentyx for the treatment of moderate-to-severe plaque psoriasis which includes the European Union countries, Switzerland, Australia, the US and Canada. In Europe, Cosentyx is the only first-line biologic approved for the systemic treatment of moderate-to-severe plaque psoriasis in adult patients. 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). In Japan, Cosentyx is approved for the treatment of moderate-to-severe plaque psoriasis and also for the treatment of PsA. In Europe, Cosentyx is approved for the treatment of PsA and AS. Cosentyx is an investigational treatment in the US for PsA and AS.

Disclaimer
The foregoing release contains forward-looking statements that can be identified by words such as "exploratory," "potential," "look forward," "suggests," "may," "investigational," or similar terms, or by express or implied discussions regarding potential new indications or labeling for Cosentyx (secukinumab), or regarding potential future revenues from Cosentyx. You should not place undue reliance on these statements. Such forward-looking statements are based on the current beliefs and expectations of management 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 Cosentyx will be submitted or approved for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that Cosentyx will be commercially successful in the future. In particular, management's expectations regarding Cosentyx could be affected by, among other things, the uncertainties inherent in research and development, including unexpected clinical trial results and additional analysis of existing clinical data; unexpected regulatory actions or delays or government regulation generally; the company's ability to obtain or maintain proprietary intellectual property protection; general economic and industry conditions; global trends toward health care cost containment, including ongoing pricing pressures; unexpected safety issues; unexpected manufacturing or quality 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, eye care and cost-saving generic pharmaceuticals. Novartis is the only global company with leading positions in these areas. In 2014, the Group achieved net sales of USD 58.0 billion, while R&D throughout the Group amounted to approximately USD 9.9 billion (USD 9.6 billion excluding impairment and amortization charges). Novartis Group companies employ approximately 120,000 full-time-equivalent associates. Novartis products are available in more than 180 countries around the world. For more information, please visit http://www.novartis.com.

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References
[1] European Medicine Agency. Remicade. Last accessed December 2015 at http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000240/human_med_001023.jsp&mid=WC0b01ac058001d124.
[2] Baeten D, Sieper J, Braun J, et al. Secukinumab, Interleukin-17A Inhibition in Ankylosing Spondylitis. New England Journal of Medicine, 2015; 373:2534-48.
[3] Sieper J, Braun J, Rudwaleit M, et al. Ankylosing spondylitis: an overview. Ann Rheum Dis. 2002; 61(Suppl III): iii8-iii18.
[4] Dougados M, Baeten D. Spondyloarthritis. Lancet; 2011;377;127-37.
[5] Novartis data on file, November 2015.
[6] Barkham N, Kong KO, & Tennant A. The unmet need for anti-tumour necrosis factor (anti-TNF) therapy in ankylosing spondylitis. Rheumatology. 2005; 44:1277-81.
[7] United Nations. World Population Prospects - The 2012 Revision. Last accessed December 2015 at http://esa.un.org/unpd/wpp/Publications/Files/WPP2012_Volume-I_Comprehensive-Tables.pdf.
[8] Dean LE, Jones GT, MacDonald AG, et al. Global prevalence of ankylosing spondylitis. Rheumatology (Oxford). 2014; 53(4):650-7.
[9] Arthritis Foundation. What is ankylosing spondylitis. Last accessed December 2015 at http://www.arthritis.org/about-arthritis/types/ankylosing-spondylitis/what-is-ankylosing-spondylitis.php.
[10] Feldtkeller E, Khan M, Van Der Heijde D, et al. Age at disease onset and diagnosis delay in HLA-B27 negative vs. Positive patients with ankylosing spondylitis. Rheum Int. 2003; 23(2):61-66.
[11] Kirkham BW, Kavanaugh A, Reich K. Interleukin-17A: a unique pathway in immune-mediated diseases: psoriasis, psoriatic arthritis and rheumatoid arthritis. Immunology. 2014; 141:133-42.
[12] Ivanov S, Linden A. Interleukin-17 as a drug target in human disease. Trends Pharmacol Sci. 2009; 30(2):95-103.

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