Novartis International AG: Novartis presents ground-breaking Phase III results showing AIN457 (secukinumab) significant efficacy in ankylosing spondylitis patients

Novartis International AG / Novartis presents ground-breaking Phase III results showing AIN457 (secukinumab) significant efficacy in ankylosing spondylitis patients . Processed and transmitted by NASDAQ OMX Corporate Solutions. The issuer is solely responsible for the content of this announcement.

• More than 60% of secukinumab 150 mg patients achieved significant improvements in AS symptoms, seen as early as Week 1 and sustained through one year of treatment[1],[2]
   
• Secukinumab is the first selective IL-17A inhibitor to significantly improve signs and symptoms of ankylosing spondylitis (AS) versus placebo in Phase III studies[1],[2]
   
• Up to 40% of AS patients have inadequate or no response to standard of care anti-TNF (tumor-necrosis-factor) medicines[3]; secukinumab is the first non anti-TNF biologic to show significant efficacy in AS patients[1],[2]
   
• Joint regulatory filings of secukinumab in AS and psoriatic arthritis are planned for 2015

             

The digital press release with multimedia content can be accessed here:
 
  (http://multimediacapsule.thomsonone.com/novartis/ain457-acr-data-as)

Basel, November 15, 2014 - Novartis announced today results from the MEASURE 1 and MEASURE 2 pivotal Phase III studies of AIN457 (secukinumab) in ankylosing spondylitis (AS). In the studies, secukinumab met the primary endpoint demonstrating rapid and statistically significant improvements versus placebo in the signs and symptoms of AS. More than 60% of secukinumab 150 mg patients achieved an ASAS20 response, a standard tool used to assess clinical improvement in AS, in MEASURE 1 (p<0.0001) and MEASURE 2 (p<0.001) [1],[2]. This is in comparison to 28.7% and 28.4% of placebo patients who achieved ASAS20 in MEASURE 1 and MEASURE 2, respectively. Detailed study results will be presented during a plenary session (MEASURE 1) and in a late breaker poster presentation (MEASURE 2) at the American College of Rheumatology (ACR) Congress in Boston, USA.

AS is a common type of spondyloarthritis (SpA), a family of long-term, inflammatory diseases impacting joints[4], which affects up to 1% of the general population[5]. Caused by spine inflammation, AS is a painful and progressively debilitating condition that can result in irreversible spinal damage reducing patients' mobility and quality of life[6].

"Ankylosing spondylitis is a debilitating condition that severely impacts patients' mobility, ability to work and overall quality of life," said Vasant Narasimhan, Global Head of Development, Novartis Pharmaceuticals. "As part of our commitment to addressing the significant unmet patient needs, we are proud to present positive Phase III results of secukinumab in ankylosing spondylitis, which marks a potential new treatment option for these patients. These ground-breaking data are expected to form the basis of joint regulatory submissions planned for 2015, which also includes results from the FUTURE 1 and FUTURE 2 psoriatic arthritis studies."

About the data at ACR
Statistically significant improvements in signs and symptoms of AS were achieved with secukinumab versus placebo at Week 16, as measured by at least 20% improvement  in the Assessment of Spondyloarthritis International Society criterion (ASAS20) [1],[2]. Improvements in secukinumab 150 mg treated patients were seen as early as Week 1 in both studies (ASAS20; p<0.01, MEASURE 1; p<0.05, MEASURE 2) and were sustained through 52 weeks of treatment, according to data from MEASURE 1[1],[2]. There are few therapeutic options available to people with AS and there is a significant unmet need for alternative treatment options[3]. Up to 40% of patients have an inadequate or no response to the current standard of care, anti-tumor-necrosis-factor (anti-TNF) medicines[3]. Importantly, clinical benefits with secukinumab were not only observed in patients who had not been previously treated with anti-TNF therapies (anti-TNF naïve), but also in patients who had an inadequate response or intolerance to anti-TNFs[1],[2]. Specifically, over twice as many secukinumab 150 mg patients (more than 45%) who had an inadequate response or intolerance to anti-TNFs achieved an ASAS20 response in MEASURE 1 and MEASURE 2 (p<0.05, MEASURE 1; p<0.05, MEASURE 2) compared to placebo patients (under 25%) in both studies[1],[2]. 

Up to 70% of patients with severe AS can develop spinal fusion (bones grow together), significantly reducing mobility and quality of life[4],[7],[8]. Patients with AS can become progressively disabled and unable to work, which may add to their reduced quality of life[4]. In both studies, treatment with secukinumab 150 mg resulted in rapid improvements in physical function and quality of life at Week 16 versus placebo as measured by the SF-36 Physical Component Summary (p<0.0001, MEASURE 1; p<0.001, MEASURE 2), with improvements sustained through 52 weeks of treatment[1],[2].

Secukinumab was well tolerated in both studies, with a safety profile consistent with that observed in the psoriasis clinical trial program involving nearly 4,000 patients[1],[2],[9]. The most common adverse events (AEs) were upper respiratory tract infection and headache[1],[2].

About Phase III secukinumab AS studies at ACR[1],[2]
MEASURE 1 and MEASURE 2 are multi-center, randomized, placebo-controlled Phase III studies to evaluate the efficacy of secukinumab in IL-17A inhibition in AS compared to placebo, and to assess the safety, tolerability and effectiveness in patients with AS. Both MEASURE 1 and MEASURE 2 evaluated secukinumab 75 mg and 150 mg versus 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 in order to confirm the clinical benefit observed in an initial proof-of-concept study. MEASURE 2 evaluated subcutaneous loading regimens. Regimens based solely on subcutaneous secukinumab therapy might be more convenient for patients, and have shown strong efficacy in other therapy areas. Both studies met their primary endpoint of ASAS20 Assessment of Spondyloarthritis International Society criteria response) and the results were consistent for the 150 mg dose:

• MEASURE 1, 60.8% and 59.7% for secukinumab 150 mg and 75 mg, respectively, versus 28.7% for placebo; p<0.0001[1],[2]
• MEASURE 2, 61.1% and 41.1% for secukinumab 150 mg and 75 mg, respectively, versus 28.4% for placebo; p<0.001 for 150 mg, p=0.0967 for 75 mg[1],[2]

Full results of secondary endpoints will be presented at ACR. Secondary endpoints at Week 16 for MEASURE 1 and MEASURE 2 included[1],[2]:

• ASAS40 response (a >=40% improvement of at least two units in each of three domains, with no worsening in the fourth domain)
• High sensitivity C-reactive protein (hs-CRP)
• ASAS 5/6 responses (>=20% improvement in five of six domains, adding spinal mobility and C-reactive protein [CRP], with no worsening in the sixth domain)
• Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), ASAS partial remission (a score of <2 units in each domain)
• BASDAI, quality of life assessed using the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the AS QoL, and ASAS partial remission

About ankylosing spondylitis (AS)                                                          
Ankylosing spondylitis (AS) is a common type of spondyloarthritis (SpA), a family of long-term diseases of joints (inflammatory disease), which also includes psoriatic arthritis (PsA)[4]. AS is a painful, progressively debilitating condition caused by inflammation of the spine. AS occurs in up to 1% of the general population and typically affects young men and women aged 25 or older[5],[10]. Certain genetic factors increase a person's risk of developing AS by more than 50%[11]. 

About secukinumab (AIN457) and interleukin-17A (IL-17A)
Secukinumab (AIN457) is a human monoclonal antibody that selectively neutralizes IL-17A[12]. Secukinumab is the first IL-17A inhibitor with positive Phase III results for the treatment of AS. Research shows IL-17A plays an important role in driving the body's immune response in psoriasis and other inflammatory arthritic diseases, including AS[13].

In addition to AS, secukinumab is also in clinical trials for the treatment of psoriatic arthritis (PsA) and rheumatoid arthritis (RA). Global regulatory applications for secukinumab in AS and PsA are planned for 2015. This follows the secukinumab global regulatory applications for moderate-to-severe plaque psoriasis which were filed in October 2013 with approvals anticipated in late 2014 or early 2015.

Disclaimer
The foregoing release contains forward-looking statements that can be identified by words such as "planned," "will," "commitment," "potential," "expected," "anticipated," or similar terms, or by express or implied discussions regarding potential marketing authorizations for AIN457, or regarding potential future revenues from AIN457. 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 AIN457 will be submitted in AS or PsA in any market, or approved for any indication, or at any particular time. Nor can there be any guarantee that AIN457 will be commercially successful in the future. In particular, management's expectations regarding AIN457 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 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, eye care, cost-saving generic pharmaceuticals, preventive vaccines, over-the-counter and animal health products. Novartis is the only global company with leading positions in these areas. In 2013, the Group achieved net sales of USD 57.9 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 133,000 full-time-equivalent associates and sell products in more than 150 countries around the world. For more information, please visit http://www.novartis.com (http://www.novartis.com).

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References
[1] Baeten D, 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 52-week phase 3 randomized placebo-controlled trial with intravenous loading and subcutaneous maintenance dosing. ACR /ARHP Annual Meeting, Boston, MA, USA, 2014. Oral presentation (presentation number 820)
[2] 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 (presentation number 536).
[3] Dougados M, Baeten D. Spondyloarthritis. Lancet. 2011; 377:2127-37.
[4] American College of Rheumatology (ACR) website. "Spondylarthritis (Spondylarthropathy)."http://www.rheumatology.org/Practice/Clinical/Patients/Diseases_And_Conditions/Spondylarthritis_(Spondylarthropathy)/ (http://www.rheumatology.org/Practice/Clinical/Patients/Diseases_And_Conditions/Spondylarthritis_(Spondylarthropathy)/). Accessed December 2013.
[5] Braun J, Bollow M, Remlinger G, et al. Prevalence of spondylarthropathies in HLA-B27 positive and negative blood donors. Arthritis Rheum. 1998;41(1):58-67.
[6] Sieper J, Braun J, Rudwaleit M, et al. Ankylosing spondylitis: an overview. Ann Rheum Dis. 2002;61(Suppl III):iii8-iii18.
[7] Lories R. The balance of tissue repair and remodeling in chronic arthritis. Nat Rev Rheumatol. 2011;7:700-07.
[8] 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.
[9] Novartis data on file. 2013: Clinical study reports for CAIN457A2302 [ERASURE] ; CAIN457A2303 [FIXTURE] ; CAIN457A2304 [SCULPTURE] ; CAIN457A2307 [JUNCTURE] ; CAIN457A2308 [FEATURE]
[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.Rheumatology International. 2003;23(2):61-66.
[11] Brown MA. Progress in studies of the genetics of ankylosing spondylitis. Arthritis Res Ther. 2009;11:254.
[12] 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.
[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.
             
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