New two year data for Novartis' Cosentyx® show sustained response and no progression in spinal damage as shown by x-ray in up to 80% of patients with ankylosing spondylitis

• A sub-study showed up to 80% of ankylosing spondylitis (AS) patients treated with Cosentyx had no radiographic progression in the spine over two years[1]

• Cosentyx demonstrated a sustained response for signs and symptoms of AS in anti-TNF naïve patients with around 80%* achieving ASAS 20 at two years[2]

• Cosentyx is the first interleukin-17A inhibitor to demonstrate efficacy in Phase III studies in AS patients[3],[4]

The digital press release with multimedia content can be accessed here:

Basel, November 8, 2015 - Novartis announced today late-breaking two year results for Cosentyx® (secukinumab) showing up to 80% of patients with ankylosing spondylitis (AS) had no radiographic progression in the spine on x-ray assessment[1]. This is the first time that data on structural spinal progression in AS have been presented for an interleukin-17A (IL-17A) inhibitor.

In addition, Cosentyx showed a sustained response in improvements of signs and symptoms, physical function and quality of life in AS patients over two years[2]. These results from an extension phase of the MEASURE 1 pivotal study were revealed at the 2015 Annual Meeting of the American College of Rheumatology (ACR) in San Francisco, United States.

Cosentyx is the first IL-17A inhibitor and the first biologic treatment other than the current standard of care - anti-tumor necrosis factor medicines (anti-TNFs) - to demonstrate efficacy in Phase III AS studies[3],[4]. AS is a life-long and painful inflammatory disease that can cause irreversible joint and/or spinal damage for patients if not treated effectively[5].

"Many patients with ankylosing spondylitis will go on to experience stiffening of the spine. Cosentyx has shown the potential to reduce structural damage of the spine in ankylosing spondylitis patients across two years," said Vasant Narasimhan, Global Head of Development, Novartis Pharmaceuticals. "Cosentyx is a real contender for becoming a new standard for treating ankylosing spondylitis patients."

These results are important because up to 70% of patients with severe AS develop spinal fusion (where the bones grow together) over 10 to 15 years, which significantly reduces mobility[6]. New treatment options are also urgently needed as many patients do not respond adequately to current medications such as non-steroidal anti-inflammatories and anti-TNF therapies with up to 40% of patients not responding sufficiently to the latter[7].

Data from 125 patients presented for Cosentyx 150 mg showed that 74%** achieved an ASAS 20 response (Assessment of Spondyloarthritis International Society response criteria) at two years***. The study enrolled patients who had either never taken, or who had previously been treated with, the current standard of care biologic, anti-TNF therapy[2]. Quality of life and physical function scores were also maintained over two years. Cosentyx was well tolerated over the two year treatment period with a safety profile consistent with that observed in previous studies across multiple indications[2].

About the study
These results are from the MEASURE 1 study and represent the longest Cosentyx AS Phase III study presented to date. MEASURE 1 is a two year, multi-center, randomized, placebo-controlled Phase III study assessing the efficacy and safety of Cosentyx in patients with active AS. The study has now entered a three year extension period. 371 patients were enrolled and administered a Cosentyx intravenous loading dose of 10 mg/kg every two weeks for the first four weeks of treatment, followed by monthly subcutaneous maintenance dosing (75 mg and 150 mg)[1]. Primary endpoints assessed superiority of Cosentyx against placebo at Week 16 in the proportion of patients achieving at least a 20% improvement in the ASAS 20 response criteria. From Week 16, patients in the placebo arm of the study were re-randomized to Cosentyx 75 mg or 150 mg based on ASAS 20 response, with non-responders switched at Week 16, and responders at Week 24[2]. In total, 103/124 and 97/125 patients randomized to Cosentyx 75 mg and 150 mg respectively completed 104 weeks. Observed analyses included in the extension phase at 104 weeks included only data available at a given time point. Patients with missing data at that time point were not included.

About ankylosing spondylitis
AS is part of a family of life-long inflammatory diseases that also includes psoriatic arthritis (PsA). It generally results in serious impairment of movement in the spine and physical function, which has an impact on quality of life. People in their teens and twenties, particularly males, are affected most often. Family members of those with AS are at higher risk[8],[9].

About Cosentyx and interleukin-17A
Cosentyx is a human monoclonal antibody that selectively neutralizes circulating IL-17A[10]. Cosentyx is the first IL-17A inhibitor with positive Phase III results for the treatment of AS and PsA[3],[4],[11],[12]. Research suggests that IL-17A may play an important role in driving the body's immune response in psoriasis, PsA and AS[13].

In October 2015, Cosentyx was recommended for approval in Europe by the Committee for Medicinal Products for Human Use (CHMP) for the treatment of AS and PsA patients.
For patients with AS and PsA, the recommended dose is Cosentyx 150 mg by subcutaneous injection with initial dosing at Weeks 0, 1, 2 and 3, followed by monthly maintenance dosing starting at Week 4. For PsA patients with concomitant moderate-to-severe plaque psoriasis, or who are anti-TNF inadequate responders, the recommended dose is Cosentyx 300 mg. Cosentyx is an investigational treatment in the US for AS and PsA.

In total, 49 countries have approved Cosentyx for the treatment of moderate-to-severe plaque psoriasis which includes the European Union and European Economic Area countries. In January 2015, Cosentyx (at a recommended dose of 300 mg in the US and EU) became the first IL-17A inhibitor approved in the EU and US for the treatment of moderate-to-severe plaque psoriasis. 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 addition, Cosentyx has been approved in Switzerland, Australia, Canada and a number of other countries for the treatment of moderate-to-severe plaque psoriasis. In Japan, Cosentyx is approved for the treatment of moderate-to-severe plaque psoriasis and also for the treatment of PsA. More than 9,600 patients have been treated with Cosentyx in clinical trials across multiple indications, and over 9,000 patients have been treated in the post-marketing setting[14].

Disclaimer
The foregoing release contains forward-looking statements that can be identified by words such as "will," "potential," "contender," "entered," "suggests," "may," "recommended," or similar terms, or by express or implied discussions regarding potential new indications or labeling for Cosentyx, or regarding potential future revenues from Cosentyx, or regarding the long-term impact of a patient's use of 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 unkno ... etc. etc.

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* Observed data
** Imputed data
*** ASAS 20 is improvement of >=20% and >=1 unit on a 10-unit scale in at least three of the four core ASAS domains, with no worsening of >=20% and >=1 unit in the fourth at 104 weeks.

References
[1] Baraliakos X, Deodhar A, Braun J et al. Effect of interleukin-17A inhibition on spinal radiographic changes through 2 years in patients with active ankylosing spondylitis: results of a phase 3 study with secukinumab. Late breaking abstract presented at the 2015 ACR/ARHP Annual Meeting, San Francisco, USA, November 10. Oral presentation number 6L.
[2] Baeten D, Braun J, Sieper J et al. Secukinumab provides sustained improvements in the signs and symptoms of active ankylosing spondylitis: 2-year efficacy and safety results from a phase 3, randomized, double-blind, placebo-controlled trial. Oral poster presented at the 2015 ACR/ARHP Annual Meeting, San Francisco, USA, November 10. Poster presentation number 2896.
[3] Sieper J, Braun J, Baraliakos X, et al. Secukinumab, a monoclonal antibody to interleukin-17A, significantly improves signs and symptoms of active ankylosing spondylitis: results of a phase 3, randomized, placebo-controlled trial with subcutaneous loading and maintenance dosing. 2014 ACR/ARHP Annual Meeting, Boston, MA, USA. Poster presentation number 536.
[4] Sieper et al. Secukinumab significantly improves signs and symptoms of active ankylosing spondylitis: 52-week data from MEASURE 2, a randomized, double-blind, placebo-controlled phase 3 trial with subcutaneous loading and maintenance dosing. 2015 EULAR Annual Meeting, Rome, Italy. Oral presentation number 168.
[5] Schett et al. Structural damage in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: traditional views, novel insights gained from TNF blockade, and concepts for the future. Arthritis Res Ther. 2011;13:S4.
[6] Barkham N, Kong K O, Tennant A, et al. The unmet need for anti-tumour necrosis factor (anti-TNF) therapy in ankylosing spondylitis. Rheumatology. 2005;44:1277-1281.
[7] Dougados M, Baeten D. Spondyloarthritis. The Lancet. 2011;377:127-37.
[8] Dean LE, Jones GT, MacDonald AG, et al. Global prevalence of ankylosing spondylitis. Rheumatology (Oxford).(link is external) 2014;53(4):650-7.
[9] American College of Rheumatology (ACR) website. "Spondyloarthritis": http://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Spondyloarthritis(link is external). Last accessed October 2015.
[10] 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.
[11] Mease, PJ, McInnes, IB, Kirkham, B, et al. Secukinumab inhibition of interleukin-17A in patients with psoriatic arthritis. N Engl J Med. 2015;373(14):1329-39.
[12] Mease, PJ, McInnes, IB, Kirkham, B, 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. The Lancet. 2015;386:9999;1137-1146.
[13] Van Baarsen LGM, Lebre MC, van der Coelen D, et al. IL-17 levels in synovium of patients with rheumatoid arthritis, psoriatic arthritis and osteoarthritis: target validation in various forms of arthritis. Ann Rheum Dis. 2011;70:A79.
[14] Novartis data on file. September 2015.


Novartis presents new two year data for Cosentyx® showing no progression in joint damage in 84% of psoriatic arthritis patients.

New x-ray assessment data, from a sub-study, showed no progression of joint structural damage in the majority of patients with psoriatic arthritis over two years[1]
•Psoriatic arthritis patients on Cosentyx maintained treatment response in joint and skin disease, physical function and quality of life over two years[1]
•Cosentyx is the first interleukin-17A inhibitor to demonstrate efficacy in Phase III studies of patients with psoriatic arthritis[2],[3]

Basel, November 8, 2015 - Novartis announced today new results for Cosentyx® (secukinumab) showing no further progression in joint damage in 84% of patients with psoriatic arthritis (PsA). In addition, Cosentyx maintained a treatment response in joint and skin disease, physical function and quality of life in patients over two years of treatment[1]. These results from the extension phase of the FUTURE 1 study were presented at the 2015 Annual Meeting of the American College of Rheumatology (ACR) in San Francisco, United States.

Cosentyx is the first of a new class of medicines called interleukin-17A (IL-17A) inhibitors to demonstrate efficacy in Phase III studies in PsA - a life-long inflammatory disease that affects the skin and joints. If not treated effectively, it can lead to irreversible joint damage and disability caused by years of inflammation[2]-[4].

"Psoriatic arthritis patients need therapies that can prevent the progression of this debilitating disease. In this two-year study, Cosentyx showed no further progression in joint damage in over 80% of PsA patients while maintaining improvements in joint and skin disease, physical function, and quality of life," said Vasant Narasimhan, Global Head of Development, Novartis Pharmaceuticals. "These results show the potential for Cosentyx to create an important new option for the treatment of psoriatic arthritis".

New medicines with an alternative way of working are needed as many patients do not achieve an adequate response from current treatments, such as disease-modifying anti-rheumatic drugs, non-steroidal anti-inflammatories or anti-tumor necrosis factor (anti-TNF) therapies. Many patients do not respond to or tolerate these therapies, with approximately 45% of PsA patients dissatisfied with their treatments[5]-[7].

These results from the FUTURE 1 study represent the longest Cosentyx Phase III study in PsA to date. Responses in joint and skin disease, physical function, and quality of life at Week 24, were maintained over two years. After two years of treatment, 67%* of patients (n=202) treated with Cosentyx 150 mg achieved the standard treatment goal of an ACR 20 response (American College of Rheumatology response criteria)[1]. In addition, 84% of patients showed no further progression in joint damage as shown by x-ray assessment**. Cosentyx was well tolerated with a safety profile consistent with that observed in previous studies[1].

About the FUTURE 1 study
FUTURE 1 is a two year, multi-center, randomized, placebo-controlled Phase III pivotal study to evaluate the efficacy of Cosentyx in patients with active PsA. FUTURE 1 enrolled 606 patients with active PsA and assessed Cosentyx with intravenous loading (10 mg/kg) and subcutaneous (75 mg and 150 mg) maintenance dosing[1]. The primary endpoint assessed superiority of Cosentyx against placebo in the proportion of patients achieving the ACR 20 response at Week 24. From Week 16, patients in the placebo arm of the study were re-randomized to receive Cosentyx 150 mg or 75 mg at either Week 16 or Week 24, based on clinical response[1]-[2].

About psoriatic arthritis
PsA is part of a family of life-long inflammatory diseases that also includes ankylosing spondylitis (AS). It is also closely associated with psoriasis. Approximately 30% of patients with psoriasis have PsA[8] and as many as one in four people with psoriasis may have undiagnosed PsA[9]. 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[4]. Up to 40% of people can suffer from joint destruction and permanent physical deformity[10].

About Cosentyx and interleukin-17A
Cosentyx is a 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 PsA and AS[2],[3],[12],[13]. Research suggests that IL-17A may play an important role in driving the body's immune response in psoriasis, PsA and AS[14].

In October 2015, Cosentyx was recommended for approval in Europe by the Committee for Medicinal Products for Human Use (CHMP) for the treatment of AS and PsA patients.
For patients with AS and PsA, the recommended dose is Cosentyx 150 mg by subcutaneous injection with initial dosing at Weeks 0, 1, 2 and 3, followed by monthly maintenance dosing starting at Week 4. For PsA patients with concomitant moderate-to-severe plaque psoriasis, or who are anti-TNF inadequate responders, the recommended dose is Cosentyx 300 mg. Cosentyx is an investigational treatment in the US for AS and PsA.

In total, 49 countries have approved Cosentyx for the treatment of moderate-to-severe plaque psoriasis which includes the European Union and European Economic Area countries. In January 2015, Cosentyx (at a recommended dose of 300 mg in the US and EU) became the first IL-17A inhibitor approved in the EU and US for the treatment of moderate-to-severe plaque psoriasis. 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 addition, Cosentyx has been approved in Switzerland, Australia, Canada and a number of other countries for the treatment of moderate-to-severe plaque psoriasis. In Japan, Cosentyx is approved for the treatment of moderate-to-severe plaque psoriasis and also for the treatment of PsA. More than 9,600 patients have been treated with Cosentyx in clinical trials across multiple indications, and over 9,000 patients have been treated in the post-marketing setting[15].

Disclaimer
The foregoing release contains forward-looking statements that can be identified by words such as "can," "could," "may," "suggests," "recommended," or similar terms, or by express or implied discussions regarding potential new indications or labeling for Cosentyx, or regarding potential future revenues from Cosentyx, or regarding the long-term impact of a patient's use of 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 ... etc. etc.

References
[1] Mease P, McInnes IB, Kirkham B, et al. Secukinumab provides sustained improvements in psoriatic arthritis: 2-year efficacy and safety results from a phase 3 randomized, double-blind, placebo-controlled trial. Presented at the 2015 ACR/ARHP Annual Meeting, San Francisco, USA, November 9. Oral presentation number 2148.
[2] Mease, PJ, McInnes, IB, Kirkham, B, et. al. Secukinumab inhibition of interleukin-17A in patients with psoriatic arthritis. N Engl J Med. 2015; 373(14):1329-39.
[3] Mease, PJ, McInnes, IB, Kirkham, B, 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. The Lancet. 2015; 386, No. 9999; p1137-1146.
[4] Mease PJ, Armstrong AW. Managing patients with psoriatic disease: the diagnosis and pharmacologic treatment of psoriatic arthritis in patients with psoriasis. Drugs. 2014; 74:423-441.
[5] Gossec L, Smolen JS, Gaujoux-Viala C, et al. European League Against Rheumatism recommendations for the management of psoriatic arthritis with pharmacological therapies. Ann Rheum Dis. 2012;71:4-12.
[6] Dougados M, Baeten D. Spondyloarthritis. The Lancet. 2011;377:127-37.
[7] Armstrong AW, et al. Undertreatment, treatment trends, and treatment dissatisfaction among patients with psoriasis and psoriatic arthritis in the United States: findings from the National Psoriasis Foundation surveys, 2003-2011. October 2013;149(10):1180-5.
[8] Zachariae H. Prevalence of joint disease in patients with psoriasis: implications for therapy. Am J Clin Dermatol. 2003; 4:441-7.
[9] National Psoriasis Foundation. Press release: Nearly one in four people with psoriasis may have undiagnosed psoriatic arthritis according to a recent study from the National Psoriasis Foundation. Last accessed October 2015 at https://www.psoriasis.org/page.aspx?pid=2197(link is external).
[10] Anwar AH, Diamond H. Psoriatic arthritis: practice essentials, background, pathophysiology and etiology. Medscape reference website: http://emedicine.medscape.com/article/2196539-overview#a6(link is external). Last accessed October 2015.
[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] Sieper J, Braun J, Baraliakos X, et al. Secukinumab, a monoclonal antibody to interleukin-17A, significantly improves signs and symptoms of active ankylosing spondylitis: results of a phase 3, randomized, placebo-controlled trial with subcutaneous loading and maintenance dosing. ACR/ARHP Annual Meeting, Boston, MA, USA, 2014. Poster presentation number 536.
[13] Sieper et al. Secukinumab significantly improves signs and symptoms of active ankylosing spondylitis: 52-Week Data from MEASURE 2. A randomized, double-blind, placebo-controlled phase 3 trial with subcutaneous loading and maintenance dosing. 2015 EULAR Annual Meeting, Rome, Italy. Presentation number 168.
[14] Van Baarsen LGM, Lebre MC, van der Coelen D, et al. IL-17 levels in synovium of patients with rheumatoid arthritis, psoriatic arthritis and osteoarthritis: Target validation in various forms of arthritis. Ann Rheum Dis. 2011;70:A79.
[15] Novartis data on file, September 2015.