Novartis presented results of two new studies at AAD: CLEAR study showed Cosentyx™ is significantly superior to Stelara® while two year extended study demonstrated its long term safety and efficacy

• In the CLEAR study presented at the American Academy of Dermatology (AAD), Cosentyx^TM showed superiority to Stelara^®* across all study endpoints up to Week 16, including PASI 100 and onset of action¹
• New data at AAD showed 7 out of 10 psoriasis patients, who were PASI 75 responders at 52 Weeks, had almost clear to clear skin (PASI 90 to PASI 100) after two years of Cosentyx^TM 300 mg treatment while almost 9 out of 10 psoriasis patients sustained their PASI 75 response²
• Cosentyx™, an IL-17A inhibitor approved for moderate-to-severe psoriasis in Canada, showed superiority to both Stelara^®* and Enbrel^{®** 1,3}  

DORVAL, QC, March 25, 2015 /CNW/ - Novartis announced results from the CLEAR study that demonstrated Cosentyx™ 300 mg (secukinumab) was significantly superior to Stelara^®* (ustekinumab), a biologic, in achieving clear or almost clear skin for psoriasis patients¹. Novartis also presented two-year results that demonstrated strong and sustained efficacy with Cosentyx™ with a favorable safety profile for the treatment of psoriasis patients². The data came from the extension study of the pivotal Phase III FIXTURE and ERASURE trials. Both detailed findings were presented in late-breaking research sessions at the 73rd Annual Meeting of the American Academy of Dermatology (AAD) in San Francisco, USA. Cosentyx™ is approved to treat adult patients with moderate-to-severe plaque psoriasis in Canada. 

"As a dermatologist, I see the physical and emotional impact moderate-to-severe plaque psoriasis inflicts on all aspects of a person's life. While psoriasis patients struggle with more than just a skin disease, achieving clear to near clear skin is an ultimate treatment goal for Canadians living with this condition," said Dr. Ron Vender, MD FRCPC, Associate Clinical Professor of Medicine at McMaster University.  "Historically, PASI 75 has been the goal for psoriasis treatments and was used regularly as the primary endpoints in clinical trials. In the CLEAR study, the primary endpoint goal was to measure both treatments capacity to achieve clear to almost clear skin or PASI 90 an important measure of treatment."

In the CLEAR Phase IIIb study, Cosentyx™ met the primary endpoint of showing superiority to Stelara^®* as assessed by the Psoriasis Area Severity Index (PASI) 90 response, known as clear to almost clear skin⁴, at Week 16 (79.0% vs. 57.6%, P<0.0001)¹. In addition, completely clear skin (PASI 100) at Week 16 was achieved by significantly more patients treated with Cosentyx™ than those receiving Stelara^®* (44.3% vs. 28.4%, P<0.0001)¹. 

"Collaboration between dermatologists at a national and international levels for the CLEAR study has provided an opportunity to discuss psoriasis management advancements and create a network of researchers dedicated to enhance psoriasis care in Canada and around the world," said Dr. Yves Poulin, clinical dermatologist and assistant professor in the Department of Medicine at Laval University. "With Cosentyx^TM we now have a new treatment option to help these Canadians."

About the CLEAR study
CLEAR (Comparison to assess Long-term Efficacy, sAfety and toleRability of secukinumab vs. ustekinumab), a 52-week, multicenter, randomized, double-blind study, is a head-to-head Phase IIIb study initiated with Cosentyx™, and compares the efficacy, long-term safety and tolerability of Cosentyx™ 300 mg (secukinumab) versus Stelara^®* (ustekinumab), in patients with moderate-to-severe plaque psoriasis¹. Twenty-four countries across North America including Canada, Europe, Asia and Australia participated in the study, with enrollment reaching 679 patients in record time¹.

The primary endpoint measured at Week 16 was PASI 90¹. Additionally the secondary endpoint measured at Week 4 is PASI 75¹. PASI 100 at Week 16 was one of the exploratory endpoints¹. Week 52 data will follow in due course.

The CLEAR study follows the pivotal Phase III FIXTURE study, which showed Cosentyx™ was superior to Enbrel^®** (etanercept) in clearing skin³. Results from the FIXTURE study were first announced in October 2013.

About the A2302E1 Extension Study (Cosentyx™Extension Study to the FIXTURE and ERASURE studies)
A2302E1 was a multicenter, double-blind, randomized withdrawal extension study to the FIXTURE and ERASURE pivotal Phase III studies. The extension study was conducted to collect long term efficacy, safety and tolerability data on Cosentyx™ in patients who achieved a PASI 75 response to Cosentyx™ at Week 52 of the FIXTURE and ERASURE core studies in moderate-to-severe plaque psoriasis.

Patients who had been receiving Cosentyx™ 300 mg or 150 mg during the maintenance period of the core studies, and who exhibited a PASI 75 response at Week 52 of the core studies, were randomized to continue the same Cosentyx™ dose or receive placebo². Patients who exhibited partial response (PASI 50 to <PASI 75 response) from baseline at Week 52 of the core studies were also eligible to enter A2302E, but did not enter the randomized withdrawal extension study². Partial responders instead continued the same treatment dose (Cosentyx™ 300 mg or 150 mg) that they received at the time of completing the maintenance period (Week 52) in the core studies. Non-responders (patients who did not achieve at least a PASI 50 response at Week 52 of the core study) were not eligible to enter any part of this extension study².

About the FIXTURE and ERASURE studies
FIXTURE (the Full year Investigative eXamination of secukinumab vs. eTanercept Using 2 dosing Regimens to determine Efficacy in psoriasis) and ERASURE (Efficacy of Response And Safety of two fixed secUkinumab REgimens in psoriasis) were part of one  of the largest Phase III program in moderate-to-severe plaque psoriasis completed to date, which involved more than 3,300 patients in over 35 countries³.

FIXTURE and ERASURE assessed the efficacy, safety and tolerability of induction period (at Week 12) and maintenance therapy (at Week 52) with subcutaneous Cosentyx™ 300 mg or 150 mg in patients with moderate-to-severe plaque psoriasis³. Both studies were multicenter, randomized, double-blind, placebo-controlled (FIXTURE: also active controlled), parallel-group Phase III trials involving 1,306 patients and 738 patients with moderate-to-severe plaque psoriasis, respectively³. Each study consisted of a 1-to-4-week screening period, a 12-week induction period, a 40-week maintenance period and an 8-week follow-up period³. FIXTURE was the first full-year blinded, direct comparison of biologic therapies for psoriasis in a Phase III study³.

The co-primary endpoints in both studies, PASI 75 response and Investigator's Global Assessment (IGA mod 2011) 0/1 response at Week 12, were used to demonstrate superiority of Cosentyx™ vs. placebo (p<0.001 for all comparisons)³. Cosentyx™ 300 mg demonstrated significant improvements in PASI 75 at Week 12 (77.1% vs. 44.0% for Enbrel^®** vs. 4.9% for placebo in FIXTURE and 81.6% vs. 4.5% for placebo in ERASURE)³.

About Cosentyx^TM (secukinumab)
Cosentyx^TM is a human monoclonal antibody (mAb) that selectively binds to interleukin-17A (IL-17A) and inhibits its interaction with the IL-17 receptor^6-11. It is approved by Health Canada for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy¹².

For more information on Cosentyx™, including contraindications, warnings and precautions, adverse reactions, drug interactions, dosing and administration, please consult the Product Monograph available at www.novartis.ca.

About PASI
The Psoriasis Area Severity Index or PASI, measures the redness, scaling and thickness of psoriatic plaques and the extent of involvement in each region of the body.

About interleukin-17A (IL-17A)
IL-17A is a naturally occurring cytokine (messenger protein) involved in normal inflammatory and immune responses^11,13. IL-17A is highly upregulated in lesional skin in contrast to non-lesional skin of plaque psoriasis patients.

About Psoriasis
Affecting as many as one million Canadians¹⁴ and more than 125 million people worldwide¹⁵, psoriasis is a chronic autoimmune disease characterized by thick and extensive skin lesions, called plaques, known to cause itching, scaling and pain¹³. People living with psoriasis reported that these symptoms can negatively impact their quality of life, both psychosocially and physically, which makes daily functioning difficult^16,17,18.

Additionally, people with psoriasis are at increased risk for other chronic illnesses¹⁷ such a psoriatic arthritis, a type of inflammatory arthritis, which about 30% of people who have psoriasis get¹⁸. Psoriasis symptoms can begin at any age, including in childhood, but the disease mainly affects adults²⁰. Symptoms start when a combination of environmental triggers and genetic factors disrupt the lifecycle of skin cells¹³.

In Canada, the prevalence of psoriasis is estimated at approximately 2%. According to a recent Canadian database study, 85% have chronic plaque psoriasis, 28% of which are considered moderate to severe¹⁹.

About Novartis in specialty dermatology
Novartis is committed to developing specialty dermatology therapies, where there are remaining high unmet medical needs.

About Novartis Pharmaceuticals Canada Inc.
Novartis Pharmaceuticals Canada Inc., a leader in the healthcare field, is committed to the discovery, development and marketing of innovative products to improve the well-being of all Canadians. In 2012, the company invested close to $100 million in research and development in Canada. Novartis Pharmaceuticals Canada Inc. employs more than 600 people in Canada. For further information, please consult www.novartis.ca.

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 and over-the-counter products. Novartis is the only global company with leading positions in these areas. In 2014, the Group achieved net sales of USD 58 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 130,000 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.

Cosentyx is a trademark.
*Stelara is a registered trademark of Janssen Biotech, Inc.
**Enbrel is a registered trademark of Amgen Inc. Enbrel used in the FIXTURE study was European sourced.

References

1.	Thaci D, Blauvelt A, Reich K, et al. Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe plaque psoriasis: 16 week results from the CLEAR study. American Academy of Dermatology 73^rd Annual Meeting. San Francisco, California. 20^th March.
2.	Secukinumab Treatment Maintains Efficacy in Moderate to Severe Plaque Psoriasis Through Second Year of Treatment: A Randomized Extension of the ERASURE and FIXTURE Studies
3.	Langley RG, Elewski BE, Lebwohl M, et al. Secukinumab in plaque psoriasis: results of two phase three trials. N Engl J Med. 2014. Jul 9;371(4):326-38.
4.	European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) Guidelines on clinical investigation of medicinal products indicated for the treatment of psoriasis. 2004. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003329.pdf Accessed February 9, 2015.
5.	Mrowietz, U. Implementing treatment goals for successful long-term management of psoriasis. Journal of the European Academy of Dermatology and Venereology, 26: 12–20. doi: 10.1111/j.1468-3083.2011.04411.x
6.	Gaffen SL. Structure and signaling in the IL-17 receptor family. Nat Rev Immunol. 2009;9(8):556-67.
7.	Ivanov S, Linden A. Interleukin-17 as a drug target in human disease. Trends Pharmacol Sci. 2009;30(2):95-103.
8.	Kopf M, Bachmann MF, Marsland BJ. Averting inflammation by targeting the cytokine environment. Nat Rev Drug Discov. 2010; 9(9):703-18.
9.	Onishi RM, Gaffen SL. Interleukin-17 and its target genes: mechanisms of interleukin-17 function in disease. Immunology. 2010;129(3):311-21.
10.	Krueger J, Fretzin S, Suárez-Fariñas M, et al. IL-17A is essential for cell activation and inflammatory gene circuits in subjects with psoriasis. J Allergy Clin Immunol. 2012;130(1):145-154.
11.	Johansen C, Usher PA, Kjellerup RB, et al. Characterization of the interleukin-17 isoforms and receptors in lesional psoriatic skin. Brit J Dermatol. 2009;160(2):319-24.
12.	Cosentyx^TM Product Monograph, Novartis Pharmaceuticals Canada Inc., March 2, 2015
13.	Nestle FO, Kaplan DH, Barker J. Psoriasis. New Engl J Med. 2009; 361: 496-509.
14.	Canadian Association of Psoriasis Patients "What is Psoriasis". Accessed February 16 2015.
15.	National Psoriasis Foundation. Facts about psoriasis. Accessed February 16 2015.
16.	Rapp SR, Feldman SR, Exum ML, Fleischer AB, Jr., Reboussin DM. Psoriasis causes as much disability as other major medical diseases. J Am Acad Dermatol. 1999; 41(3 Pt 1):401-7.
17.	Farley E et al. Psoriasis: comorbidities and associations. G Ital Dermatol Venereol. 2011 Feb;146(1):9-15
18.	National Psoriasis Foundation website. "Health conditions associated with psoriasis". Accessed February 16 2015.
19.	Petrella RJ, Gregory V, Luciani L, Barbeau M . Characteristics of chronic plaque psoriasis in Canada: a retrospective database study. (PSS7) Poster presented at ISPOR 19th Annual International Meeting, Montréal, QC, Canada, May 2014
20.	Raval K, Lofland JH, Waters HC, Tak Piech C. Disease and treatment burden of psoriasis: Examining the impact of biologics. J Drugs Dermatol 2011; 10(2):189-96

SOURCE Novartis Pharmaceuticals Canada Inc.

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