Novartis International AG: Novartis reports landmark Phase III results for AIN457 (secukinumab) showing rapid and significant efficacy in psoriatic arthritis patients

Novartis International AG / Novartis reports landmark Phase III results for AIN457 (secukinumab) showing rapid and significant efficacy in psoriatic arthritis patients . Processed and transmitted by NASDAQ OMX Corporate Solutions. The issuer is solely responsible for the content of this announcement.

• Secukinumab demonstrated significant and sustained efficacy versus placebo in improving signs and symptoms of active psoriatic arthritis (PsA) in two pivotal studies[1]-[4] 

• FUTURE 1 and FUTURE 2 are the first Phase III studies of a selective IL-17A inhibitor in PsA, a painful, debilitating condition causing inflammation of joints and skin[5],[6]

• In FUTURE 1 more than 80% of secukinumab-treated patients experienced no progression of joint structural damage, which affects two-thirds of PsA patients[1],[2],[7],[8] 

• In both studies, secukinumab demonstrated rapid, significant and sustained improvements in skin psoriasis consistent with Phase III psoriasis study results[1]-[4],[9]

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

(http://multimediacapsule.thomsonone.com/novartis/ain457-acr-data-psa)

Basel, November 16, 2014 - Novartis announced today first ever results from the pivotal Phase III FUTURE 1 and FUTURE 2 studies showing AIN457 (secukinumab) demonstrated rapid and significant clinical improvements versus placebo in improving the signs and symptoms of psoriatic arthritis (PsA). PsA is part of a family of long-term diseases impacting joints, known as spondyloarthritis (SpA), which also includes ankylosing spondylitis[10]. There is a high unmet treatment need for patients with PsA. Many patients  do not respond to, or tolerate, anti-TNF (tumor-necrosis-factor) medicines, the current standard of care and approximately 45% of people are dissatisfied with current treatments[5],[11]-[13]. Secukinumab stops the action of interleukin-17A (IL-17A), which is central to the development of inflammatory diseases[14],[15]. These results are being presented today at the American College of Rheumatology (ACR) Congress in Boston, USA.

"We are thrilled to present these landmark Phase III results of secukinmab in PsA, a painful and debilitating condition, with a significant unmet treatment need for patients," said Vasant Narasimhan, Global Head of Development, Novartis Pharmaceuticals. "We are committed to addressing unmet medical needs in rheumatology by bringing highly effective and long-lasting therapies to patients and these important data are expected to form the basis of our regulatory filing submission in PsA planned in 2015."

About the data at ACR
Clinically and statistically significant improvements in signs and symptoms of PsA were achieved versus placebo, as measured by a 20% reduction in the American College of Rheumatology response criteria (ACR 20), a standard tool used to assess improvement at Week 24[16]. Between 50% to 54% of secukinumab patients achieved at least ACR 20 in both FUTURE 1 (150 mg; p<0.0001) and FUTURE 2 (150 and 300 mg; p<0.0001)[1]-[4]. This is in comparison to 17.3% and 15.3% of placebo patients who achieved ACR 20 in FUTURE 1 and FUTURE 2, respectively[1]-[4].

Secukinumab patients in all dose groups experienced rapid onset of effect as early as Week 1 in FUTURE 1 (p<0.0001) and Week 3 in FUTURE 2 (150 mg p<0.0001 and 300 mg p<0.001) [1]-[4]. Long-term data from FUTURE 1 also confirmed these improvements were sustained through 52 weeks of treatment[1],[2]. Importantly, clinical benefits with secukinumab were observed in patients who had not been previously treated with anti-TNF therapies (anti-TNF naïve), the current standard of care for PsA, and also in patients who had an inadequate or no response to anti-TNFs[1],[2],[12],[13]. Those who had prior exposure to anti-TNFs included 29.5% and 35% of study participants in FUTURE 1 and FUTURE 2, respectively[1]-[4].

In FUTURE 1, more than 80% of patients experienced no progression of joint structural damage, which is suffered by approximately two-thirds of patients with PsA, and is associated with loss of function and disability[1],[2],[5],[6]. Improvements in joint damage were shown in both anti-TNF naïve patients and in the patients with inadequate or no response to anti-TNFs[1],[2]. Additionally, secukinumab demonstrated rapid, significant and sustained improvements in skin psoriasis in both FUTURE 1 and FUTURE 2 which was consistent to results of the Phase III psoriasis studies[1]-[4],[9].

Secukinumab was well tolerated in both studies, with a safety profile that was consistent with that observed in the large psoriasis clinical trial program involving nearly 4,000 patients[1]-[4],[17]. The most common adverse events (AEs) were the common cold, headache and upper respiratory tract infection[1]-[4],[17].

About Secukinumab Psoriatic Arthritis Phase III trials
FUTURE 1 and FUTURE 2 are the first multi-center, randomized, placebo-controlled Phase III studies to evaluate the efficacy of secukinumab in IL-17A inhibition in PsA. In the FUTURE 1 study patients received an intravenous loading dose every two weeks for the first four weeks of treatment followed by monthly subcutaneous doses of 75 mg or 150 mg compared to placebo, and FUTURE 2 compared subcutaneous loading dose secukinumab 75 mg, 150 mg and 300 mg to placebo[1]-[4]. The intravenous loading period used in FUTURE 1 was designed to provide high systemic exposure for induction of response, in keeping with the initial proof of concept study in PsA with secukinumab[1],[2]. FUTURE 2 utilized an administration route (subcutaneous loading dose) and dose range (up to 300 mg) that is more consistent with the psoriasis program[3],[4]. A combined total of more than 1,000 patients were enrolled in the studies[1]-[4].

Both studies met their primary endpoint, the American College of Rheumatology response criteria (ACR 20) at Week 24 - a standard tool used to assess improvement (at least 20% improvement) in PsA signs and symptoms - and findings were consistent across the two studies[1]-[4],[16]:

• FUTURE 1, 50.5% and 50.0% for both secukinumab treatment arms, respectively, versus 17.3% for placebo; p<0.0001
• FUTURE 2, 29.3% for secukinumab 75 mg (p<0.05); 51.0% and 54.0% for secukinumab 150 mg and 300 mg, respectively, versus 15.3% for placebo; p<0.0001

Full results of secondary endpoints will be presented at ACR. Secondary endpoints at Week 24 in FUTURE 1 and FUTURE 2 included[1]-[4]:

• 75% and 90% improvement in Psoriasis Area-and-Severity Index score (PASI 75 and PASI 90)
• Change from baseline in 28-joint Disease Activity Score using C-reactive protein (DAS28 - CRP)
• Physical function assessed using the Medical Outcome Short Form (36) Health Survey physical component summary scores (SF-36 PCS) 
• Physical function assessed using the Health Assessment Questionnaire Disability Index (HAQ-DI)
• ACR 50 (American College of Rheumatology response criteria) response
• Proportion of subjects with dactylitis and enthesitis
• Overall safety and tolerability of each secukinumab regimen compared with placebo

Additional secondary endpoint at Week 24 in FUTURE 1[1]-[2]:

• Radiographic progression assessed using the van der Heijde modified total Sharp score (mTSS)

             
About psoriatic arthritis (PsA)
Closely associated with psoriasis, psoriatic arthritis (PsA) is part of a family of long-term diseases impacting joints, known as spondyloarthritis (SpA); approximately 30% of patients with psoriasis have psoriatic arthritis[10],[11]. Psoriatic arthritis (PsA) is a debilitating, long-lasting inflammatory disease linked with significant disability, poor quality of life and reduced life expectancy[11]. PsA is associated with joint pain and stiffness, skin and nail psoriasis, swollen toes and fingers, persistent painful tendonitis, and irreversible joint damage[6]. Between 0.3% and 1% of the general population may be affected by PsA and as many as one in four people with psoriasis may have undiagnosed PsA[11],[15].

About secukinumab (AIN457) and interleukin-17A (IL-17A)
Secukinumab (AIN457) is a human monoclonal antibody that selectively neutralizes IL-17A[14]. Secukinumab is the first IL-17A inhibitor with positive Phase III results for the treatment of PsA and AS. Research shows that IL-17A plays an important role in driving the body's immune response in psoriasis and other inflammatory arthritic diseases, including PsA and AS[15].

In addition to PsA, secukinumab is also in clinical trials for the treatment of ankylosing spondylitis (AS) 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 "committed," "expected," "planned," "may," "will," 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 operate 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] Mease PJ, McInnes IB, Kirkham B, et al. Secukinumab, a human anti-interleukin-17A monoclonal antibody, improves active psoriatic arthritis and inhibits radiographic progression: efficacy and safety data from a phase 3 randomized, multicenter, double-blind, placebo-controlled study. Oral presentation at: ACR/ARHP Annual Meeting, Boston, MA, USA, 2014. Presentation number 948.
[2] Novartis data on file. 2014. FUTURE1 clinical study report.
[3] McInnes IB. Secukinumab, a Human Anti-Interleukin-17A Monoclonal Antibody, Improves Active Psoriatic Arthritis: 24-Week Efficacy and Safety Data from a Phase 3 Randomized, Multicenter, Double-Blind, Placebo-Controlled Study Using Subcutaneous Dosing. Oral presentation at: ACR/ARHP Annual Meeting, Boston, MA, USA, 2014. Presentation number.
[4] Novartis data on file. 2014. FUTURE 2 clinical study report.
[5] Boehncke WH, Menter A. Burden of disease: psoriasis and psoriatic arthritis. Am J Clin Dermatol. 2013;14:377-88.
[6] Mease PJ, Armstrong AW. Managing patients with psoriatic disease: the diagnosis and pharmacologic treatment of psoriatic arthritis in patients with psoriasis. Drugs. 2014;74:423-41.
[7] van der Heijde D, Landewé R, Mease P, et al. Secukinumab, A Monoclonal Antibody to Interleukin-17A, Provides Significant and Sustained Inhibition of Joint Structural Damage in Active Psoriatic Arthritis Regardless of Prior TNF Inhibitors or Concomitant Methotrexate: a Phase 3 Randomized, Double-Blind, Placebo-Controlled Study. Oral presentation at: ACR/ARHP Annual Meeting, Boston, MA, USA, 2014. Presentation number 954.
[8] Coates LC, Navarro-Coy N, Brown SR, et al. The TICOPA protocol (TIght COntrol of Psoriatic Arthritis): a randomised controlled trial to compare intensive management versus standard care in early psoriatic arthritis. BMC Musculoskelet Disord. 2013;21;14:101.
[9] Langley RG, Elewski BE, Lebwohl M, et al. Secukinumab in Plaque Psoriasis - Results of Two Phase Three Trials. N Engl J Med. 2014; 371(4):326-338.
[10] 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.
[11] Gladman DD, Antoni C, Mease P, et al. Psoriatic arthritis: epidemiology, clinical features, course, and outcome. Ann Rheum Dis. 2005; 64:ii14-ii17.
[12] 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.
[13] Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 6: guidelines of care for the treatment of psoriasis and psoriatic arthritis: case-based presentations and evidence-based conclusions. J Am Acad Dermatol. 2011;65:137-74.
[14] 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.
[15] 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.
[16] Felson DT (http://www.ncbi.nlm.nih.gov/pubmed?term=Felson%20DT%5BAuthor%5D&cauthor=true&cauthor_uid=7779114), Anderson JJ (http://www.ncbi.nlm.nih.gov/pubmed?term=Anderson%20JJ%5BAuthor%5D&cauthor=true&cauthor_uid=7779114), Boers M (http://www.ncbi.nlm.nih.gov/pubmed?term=Boers%20M%5BAuthor%5D&cauthor=true&cauthor_uid=7779114), et al. American College of Rheumatology. Preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum (http://www.ncbi.nlm.nih.gov/pubmed/?term=Felson+and+ACR+and+1995). 1995;38:727-35.
[17] Novartis data on file. 2013: Clinical study reports for CAIN457A2302 [ERASURE] ; CAIN457A2303 [FIXTURE] ; CAIN457A2304 [SCULPTURE] ; CAIN457A2307 [JUNCTURE] ; CAIN457A2308 [FEATURE].

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