Novartis and Servier sign licensing agreement for a novel treatment of Major Depressive Disorder

* Once-daily treatment in Phase III with a novel mechanism of action as potential innovation for the pharmacological treatment of depression
* Novartis acquires exclusive development and marketing rights to the US and several other countries.

Basel, Switzerland, March 29, 2006 - Novartis and Servier announced today the signing of a licensing agreement for agomelatine, a Phase III investigational drug for the treatment of major depressive disorder, a condition estimated to affect one in ten adults in the US alone.

Under development as a once-daily treatment, agomelatine is a novel melatonergic antidepressant that acts as an agonist at MT1 and MT2 receptors with additional 5-HT2c antagonist properties. Due to its unique receptor profile, agomelatine represents a potential innovation for the pharmacological treatment of depression.

Under the terms of the agreement, which requires antitrust approval in the United States, Novartis has acquired the exclusive rights to further develop and market agomelatine in the US and several other countries. Servier retained the rights to develop and market the product in the rest of the world. Financial terms of this agreement were not disclosed.

“This collaboration shows our commitment to invest in promising and innovative compounds like agomelatine to further strengthen our portfolio,” said James Shannon, Head of Development, Novartis Pharma AG. “With the initiation of a clinical development program for agomelatine in the US, Novartis will be able to build on its leadership position in neurology and potentially become a key player in the field of psychiatric disorders such as depression.”

Approximately one out of 10 adults in the US will suffer from a depressive illness in a given year[1]. Depression is the leading cause of disability in the US, resulting in more days of disability than other chronic medical conditions like heart disease, hypertension, diabetes and lower back pain and is the principal cause of suicide in the US[2]. Despite the growing awareness of depression in the general population, it is estimated that only about half of patients with depression are diagnosed[3] and only 22% are adequately treated with an antidepressant[4]. Of those patients treated, discontinuation and/or switching of current medication often occurs due to either efficacy or tolerability concerns.


The efficacy, tolerability and safety of agomelatine has been assessed in several double-blind, randomized, placebo- and active-controlled Phase III studies conducted by Servier, mainly in Europe, Canada and Australia. In the active-controlled studies, which utilized a commonly prescribed product for the treatment of major depression, the effect of agomelatine was similar to that of the active-control.

In general, the number of adverse events experienced in patients treated with agomelatine during these studies was comparable to placebo. The main adverse events were dizziness, headache and nausea8. Additionally, the tolerability and safety profile of agomelatine includes a lack of clinically significant weight gain, no apparent effects on sexual function (particularly as compared with the active-control), a low incidence of gastro-intestinal adverse events as well as absence of discontinuation symptoms upon withdrawal[5],[6],[7],[8]. These side effects, often observed with current therapies, contribute to non-adherence or discontinuation of therapy[6],[8].

Disturbances of circadian rhythms, especially alterations of the sleep-wake rhythm, are strongly associated with depressive states. Sleep disturbances are among the most frequent complaints and can be observed in up to 80% of depressive patients[9]. Agomelatine restores restful sleep and improves daytime alertness[10] by normalizing the timing and continuity of sleep in depressive patients.

About Major Depression
Essential features of a major depression are depressed mood, loss of interest in daily life activities, weight loss (or gain), decrease of appetite, sleep disturbances, feeling of worthlessness and/or of guilt, presence of suicidal ideation or behavior[11]. The average age of onset of symptoms peaks between ages 30 - 45, but diagnosis is often not made until some years later. Depression is often chronic and recurrent, as 55-70% of individuals with a single episode can be expected to have a second episode and over 80% of individuals who experience a second episode have a third within three years without treatment[12].

This release contains certain forward-looking statements relating to the Company’s business, which can be identified by the use of forward-looking terminology such as “goal is”, “potentially become”, “will be able”, “will suffer”, or similar expressions, or by express or implied discussions regarding potential indications for agomelatine, the potential that agomelatine will be approved for marketing, or regarding potential future revenue from agomelatine. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results with agomelatine to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that agomelatine will be approved for any indications in any market or regarding potential future revenue from agomelatine. In particular, management’s expectations regarding commercialization of agomelatine could be affected by, among other things, additional analysis of agomelatine clinical data; new clinical data; unexpected clinical trial results; unexpected regulatory actions or delays in government regulation generally; the company’s ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; government, industry, and general public pricing pressures; as well as factors discussed in the Company’s Form 20-F filed with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described herein as anticipated, believed, estimated or expected. 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 has been a leader in the neuroscience area for more than 50 years, having pioneered early breakthrough treatments for Alzheimer’s disease, Parkinson’s disease, attention deficit/hyperactivity disorder, epilepsy, schizophrenia and migraine. Novartis continues to be active in the research and development of new compounds, is committed to addressing unmet medical needs and to supporting patients and their families affected by these disorders.

Novartis AG (NYSE: NVS) is a world leader in offering medicines to protect health, treat disease and improve well-being. Our goal is to discover, develop and successfully market innovative products to treat patients, ease suffering and enhance the quality of life. Novartis is the only company with leadership positions in both patented and generic pharmaceuticals. We are strengthening our medicine-based portfolio, which is focused on strategic growth platforms in innovation-driven pharmaceuticals, high-quality and low-cost generics and leading self-medication OTC brands. In 2005, the Group’s businesses achieved net sales of USD 32.2 billion and net income of USD 6.1 billion. Approximately USD 4.8 billion was invested in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 91,000 people and operate in over 140 countries around the world. For more information, please visit http://www.novartis.com.


References

[1] National Institute of Mental Health: The Numbers Count: Mental Illness in America; August 1999.
[2] The State of Depression in America, Depression and Bipolar Support Alliance, Feb 2006
[3] Kessler RS. National Comorbidity Study (NCS), 1994
[4] Kessler RC et al. The Epidemiology of Major Depressive Disorder. JAMA 2003, 289: 3095-3105.
[5] Loo et al., Determination of the dose of agomelatine, a melatoninergic agonist and selective 5-HT(2C) antagonist, in the treatment of major depressive disorder: a placebo-controlled dose range study. Int Clin Psychopharmacol. 2002;17(5):239-47.
[6] Mongomery SA et al., Absence of discontinuation symptoms with agomelatine and occurrence of discontinuation symptoms with paroxetine: a randomized, double-blind, placebo-controlled discontinuation study.Int Clin Psychopharmacol. 2004;19(5):271-80.
[7] Kennedy SH, Emsley R, Placebo-controlled trial of agomelatine in the treatment of major depressive disorder. Eur Neuropsychopharmacol. 2006 16:93-100.
[8] Rouillon F, Efficacy and tolerance profile of agomelatine and practical use in depressed patients.Int Clin Psychopharmacol. 2006;21 Suppl 1:31-5.
[9] Tsuno N., Besset A., Ritchie K. “Sleep and Depression” J Clin Psychiatry 2005; 66:1254-1269.
[10] Lam RW, Sleep disturbances and depression: a challenge for antidepressants. Int Clin Psychopharmacol. 2006, 21; Suppl 1: S25-9.
[11] American Psychiatric Association, (1994) DSM-IV Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition); Washington, D.C
[12] Frank, E. & Thase, M.E. (1999). Natural history and preventative treatment of recurrent mood disorders. Annual Review of Medicine, 50, 43-468.

The information in the press releases on these pages was factually accurate on the date of publication. These press releases remain on Novartis’ website for historical purposes only. Novartis assumes no duty to update the information to reflect subsequent developments. Readers should not rely upon the information in these pages as current or accurate after their publication dates.

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Novartis AG

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