Novartis announces Phase III study shows AMG 334 significantly reduces monthly migraine days in people with episodic migraine

Novartis International AG / Novartis announces Phase III study shows AMG 334 significantly reduces monthly migraine days in people with episodic migraine . Processed and transmitted by Nasdaq Corporate Solutions. The issuer is solely responsible for the content of this announcement.

• ARISE, first pivotal Phase III study of AMG 334 (erenumab) in episodic migraine prevention, met primary endpoint, showing a statistically significant reduction in monthly migraine days vs placebo
   
• People with episodic migraine experience up to 14 migraine days each month and lose a substantial part of their lives to this debilitating disease
   
• AMG 334 is being co-developed by Novartis and Amgen

Basel, September 28, 2016 - Novartis today announced positive topline results from ARISE, the first Phase III study evaluating the efficacy and safety of monthly subcutaneous AMG 334 (erenumab) 70mg in episodic migraine prevention. The study met the primary endpoint, demonstrating a statistically significant reduction from baseline in monthly migraine days in patients treated with AMG 334 compared with placebo at 12 weeks.[1] AMG 334 is specifically designed to prevent migraine by blocking the Calcitonin Gene-Related Peptide (CGRP) receptor that is believed to have a critical role in mediating the incapacitating pain of migraine.[2]

"People who suffer from episodic migraine experience substantial pain, disability and physical impairment, which can significantly disrupt their ability to participate in everyday activities," said Vasant Narasimhan, Global Head Drug Development and Chief Medical Officer for Novartis. "The positive results from ARISE are especially encouraging because there are currently no treatment options specifically designed for the prevention of migraine. These findings, in combination with the recent positive data in chronic migraine prevention, add to the growing body of evidence that shows AMG 334 has the potential to help individuals worldwide suffering from episodic and chronic migraine."

A total of 577 patients enrolled in ARISE were randomized to receive either placebo or AMG 334 at 70mg subcutaneously, once monthly.[1],[3] Patients experienced between four and 14 migraine days each month, with an average of eight migraine days per month at baseline.[1],[3] Those receiving AMG 334 experienced a statistically significant 2.9-day reduction from baseline in monthly migraine days, as compared to a 1.8-day reduction in the placebo arm.[1]

The safety profile of AMG 334 was similar to placebo and consistent with previously-reported studies.[1] The most common adverse events were upper respiratory tract infection, injection site pain, and nasopharyngitis.[1]

Further analysis of the ARISE data is ongoing, and will be submitted to a future medical meeting and for publication. The STRIVE study, a second Phase III episodic migraine study evaluating both 70mg and 140mg doses of AMG 334 for 24 weeks, is expected to be completed by the end of this year. Positive results from a Phase II study of AMG 334 in chronic migraine prevention were also announced earlier this year.[4]

Migraine is more than just a headache; it is the most prevalent of all neurological disorders and affects more than 10% of the worldwide population.[5]-[8] Migraine has a profound and limiting impact on an individual's abilities to carry out everyday tasks, and was declared by the World Health Organization to be one of the top 10 causes of years lived with disability for men and women.[9], [10] People with episodic migraine experience up to 14 migraine days each month.[11]

AMG 334 is being co-developed by Amgen and Novartis. As part of the collaboration, Amgen retained commercialization rights in the U.S., Canada and Japan, and Novartis has rights in Europe and the rest of the world.

About the ARISE Study (NCT02483585)
The ARISE study (NCT02483585) is a global Phase III, multicenter, randomized 12-week, double-blind, placebo-controlled study evaluating the safety and efficacy of AMG 334 in episodic migraine prevention.[3] In the study, 577 patients were randomized to receive once-monthly subcutaneous placebo or AMG 334 (70mg) in a 1:1 ratio.[1],[3] Patients enrolled in ARISE were experiencing between four and 14 migraine days each month.[3] The primary endpoint was change in monthly migraine days from baseline to the last four weeks of the 12-week treatment phase in patients with episodic migraine (the number of migraine days between weeks nine and 12). [3] Secondary study endpoints included the proportion of patients with a reduction of at least 50% from baseline in monthly migraine days and change from baseline in monthly acute migraine-specific medication days in the last four weeks of the double-blind treatment phase. [3] The impact of migraine on physical function and the impact on everyday activities were each assessed as secondary endpoints by the Migraine Physical Function Impact Diary (MPFID), a scale developed to measure these two domains. [3]

About Migraine
Migraine involves recurrent attacks of moderate to severe head pain that is typically pulsating, often unilateral and associated with nausea, vomiting and sensitivity to light, sound and odors.[12] Migraine is associated with personal pain, disability and reduced quality of life, and financial cost to society.[13] It remains under-recognized and under-treated with more than 40% of people going undiagnosed.[13],[14] Worldwide, approximately 90% of people diagnosed with migraine have episodic migraine, which is characterized by one to 14 migraine days a month.[11],[15] The remaining 10% have chronic migraine, which is characterized by at least 15 headache days per month, of which eight or more days have migraine features, for more than three months.[15],[16]

About AMG 334 (erenumab)
AMG 334 (erenumab) is a fully human monoclonal antibody specifically designed for the prevention of migraine. AMG 334 targets and blocks the Calcitonin Gene-Related Peptide (CGRP) receptor, believed to have a critical role in mediating the incapacitating pain of migraine. AMG 334 is currently being studied in several large global, randomized, double-blind, placebo-controlled trials to assess its safety and efficacy in migraine prevention.

About the Amgen and Novartis Neuroscience Collaboration
In August 2015, Novartis entered into a global collaboration with Amgen to jointly develop and commercialize pioneering neuroscience treatments in the field of Alzheimer's Disease (AD) and migraine. The companies are partnering in the development and commercialization of a beta-secretase 1 (BACE) inhibitor program in AD. Novartis' oral therapy CNP520 (currently in a Phase II study for AD) will be the lead molecule and further compounds from both companies' pre-clinical BACE inhibitor programs may be considered as novel follow-on molecules. The collaboration also focuses on innovative investigational Amgen drugs in the migraine field, including AMG 334 (currently in Phase III studies for episodic migraine and a Phase II study for chronic migraine) and AMG 301 (currently in a Phase I study). For the migraine program, Novartis will have global co-development rights and commercial rights outside the U.S., Canada, and Japan.

About Novartis in Neuroscience
Novartis has a strong ongoing commitment to neuroscience (NS) and to bringing innovative treatments to patients suffering from neurological conditions where there is a high unmet need. We currently offer patients and physicians a large drug portfolio encompassing Multiple Sclerosis (MS), Alzheimer's disease, Parkinson's disease, Epilepsy and Attention Deficit Hyperactivity Disorder, and have a promising pipeline in MS, Alzheimer's disease, migraine and specialty neurology (e.g. neuropathic pain).

Disclaimer
The foregoing release contains forward-looking statements that can be identified by words such as "believed to," "can," "encouraging," "growing," "potential," "ongoing," "will," "expected," "being studied," "pioneering," "may," "investigational," "commitment," "pipeline," or similar terms, or by express or implied discussions regarding potential marketing approvals for AMG 334, CNP520 and AMG 301, potential new indications or labeling for products in the Novartis Neuroscience portfolio, or regarding potential future revenues from such investigational compounds and products. 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 AMG 334, CNP520 or AMG 301 will be submitted or approved for sale in any market, or at any particular time. Neither can there be any guarantee that any product in the Novartis Neuroscience portfolio 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 AMG 334, CNP520, AMG 301 or any product in the Novartis Neuroscience portfolio will be commercially successful in the future. In particular, management's expectations regarding such investigational compounds and products 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, quality or 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 and cost-saving generic pharmaceuticals. Novartis is the only global company with leading positions in these areas. In 2015, the Group achieved net sales of USD 49.4 billion, while R&D throughout the Group amounted to approximately USD 8.9 billion (USD 8.7 billion excluding impairment and amortization charges). Novartis Group companies employ approximately 118,000 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] Novartis data on file
[2] Bigal ME et al. Calcitonin Gene-Related Peptide (CGRP) and Migraine Current Understanding and State of Development. Headache. 2013;53(8):1230-1244.
[3] ClinicalTrials.gov. Study to Evaluate the Efficacy and Safety of AMG 334 Compared to Placebo in Migraine Prevention (ARISE). https://clinicaltrials.gov/ct2/show/NCT02483585?term=ARISE+amg+334&rank=1 (link is external). Accessed September 2016.
[4] Novartis presents new positive data at EHMTIC showing AMG 334 significantly reduces monthly migraine days in chronic migraine. https://www.novartis.com/news/media-releases/novartis-presents-new-positive-data-ehmtic-showing-amg-334-significantly-reduces. Accessed September 2016.
[5] Edvinsson L. CGRP receptor antagonists and antibodies against CGRP and its receptor in migraine treatment. Br J Clin Pharmacol. 2015;80(2):193-9.
[6] Hirtz D et al. How common are the "common" neurologic disorders? Neurology. 2007; 68(5):326-37.
[7] Vos T et al. Global Burden of Disease Study. Lancet. 2015;386(9995):743-800.
[8] Stovner L et al. The global burden of headache: a documentation of headache prevalence and disability worldwide. Cephalalgia. 2007;27(3):193-210.
[9] Buse DC et al. Assessing and Managing All Aspects of Migraine: Migraine Attacks, Migraine-Related Functional Impairment, Common Comorbidities, and Quality of Life. Mayo Clin Proc. 2009;84(5):422-435.
[10] World Health Organization. Estimates for 2000-2012. Disease Burden. 2012.
[11] Katsarava Z et al. Chronic migraine: Classification and comparisons. Cephalalgia. 2011;31:520-529.
[12] National Institute for Neurological Disorders and Stroke. Headache: Hope Through Research. http://www.ninds.nih.gov/disorders/headache/detail_headache.htm (link is external). Accessed September 2016.
[13] World Health Organization. Headache disorders. http://www.who.int/mediacentre/factsheets/fs277/en/ (link is external). Accessed September 2016.
[14] Diamond S et al. Patterns of Diagnosis and Acute and Preventive Treatment for Migraine in the United States: Results from the American Migraine Prevalence and Prevention Study. Headache. 2007;47(3):355-63.
[15] National Migraine Centre. What is migraine? http://www.nationalmigrainecentre.org.uk/migraine-and-headaches/migraine-and-headache-factsheets/what-is-migraine/ (link is external). Accessed September 2016.
[16] Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013;33:629-808.

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