New Data Supports Valdoxan's(R) Unique Clinical Signature

AMSTERDAM, August 31, 2010 - Valdoxan(R)/Thymanax(R) (agomelatine) is more efficacious than
both conventional selective serotonin reuptake inhibitor (SSRI) and serotonin
noradrenaline reuptake inhibitor (SNRI) antidepressants, according to new
data presented today at the 23rd European College of Neuropsychopharmacology
(ECNP) Congress.

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This new data supports the unique clinical signature of
Valdoxan(R), already documented by a significant and continuous improvement
of the patient condition from the first days of treatment, for a true
recovery of depression and effective protection against relapse.[1],[2],[3]

New data[4]

The new data is a result of a pooled analysis of four multicentre,
international, randomised, double-blind, parallel-group studies involving
outpatients with major depressive disorder (MDD). In each of these individual
studies, agomelatine demonstrated to offer a distinctive profile of efficacy
leading to an improved treatment of depression.

Agomelatine was compared head-to-head with SSRI (sertraline
50-100 mg, escitalopram 10-20 mg or fluoxetine 20-40 mg) and SNRI
antidepressants (venlafaxine 75-150 mg) after six to eight weeks of
treatment. Efficacy was assessed using the HAM-D17 total score scale. The
overall analysis included 643 patients treated with agomelatine and 657
randomised to SSRI/SNRI therapy.

Agomelatine showed significantly greater antidepressant
efficacy than SSRI and SNRI comparators in terms of both HAM-D17 improvement
and percentage of responders. Over the treatment period, there was a
significant 1.37 point difference on the HAM-D17 total score in favour of
agomelatine (p<0.001). Agomelatine's higher efficacy was also evident in the
percentage of responders - patients whose depression improved by a (greater
than or equal to) 50% decrease in baseline total HAM-D17 score. Overall,
71.75% of patients achieved a response to agomelatine, versus 64.52% of
subjects on SSRIs/SNRI - a statistically significant difference in favour of
agomelatine (p=0.005).

"This new data adds to the already compelling clinical
evidence for Valdoxan's efficacy in treating major depressive disorder, even
in its severe forms," notes Professor Siegfried Kasper, Department of
Psychiatry and Psychotherapy, University Hospital, Vienna, Austria.
"Valdoxan's(R) excellent antidepressant efficacy - coupled with a unique,
'first-of-a-kind' mode of action - marks Valdoxan(R) out as an exciting and
innovative treatment for depressed patients."

In patients with severe depression, agomelatine also performed
significantly better than SSRI and SNRI comparators. This severe
subpopulation included 1013 patients (499 treated with agomelatine and 514
with SSRIs/SNRIs) with a baseline HAM-D17 score (greater than or equal to)
25. Agomelatine's antidepressant efficacy again proved significantly better
than SSRIs/SNRIs as evidenced by a significant difference in HAM-D17 total
score in favour of agomelatine (p=0.014) and a significantly higher
percentage of patients responding to agomelatine (71.54% versus 65.29%,
p=0.005).

A unique adherence to treatment[5]

Agomelatine's clinical efficacy is enhanced by greater
adherence to treatment, where patients continue to take their medication as
prescribed. Adherence is a key factor in deriving maximal therapeutic benefit
from antidepressant medication. Greater adherence to agomelatine is supported
by results from the new meta analysis which found that significantly less
patients on agomelatine (6.3%) withdrew from trials due to treatment-emergent
adverse events, compared to SSRIs/SNRI (10.5%) (p=0.0058).

Valdoxan(R): a major therapeutic advance in management of depression

"Although we have a large armoury at our disposal, gaps still
exist in modern depression management" says Professor Raymond Lam, Department
of Psychiatry, University of British Columbia, Vancouver, Canada. "As the
first-ever antidepressant to target melatonergic MT1 and MT2 receptors and
5-HT2C receptor, with no impact on serotonin levels, Valdoxan offers a new
approach to tackling this devastating disease."

Valdoxan(R) is the result of an advanced pharmacological
research programme involving investigation centres all around the world. It
is the first antidepressant that simultaneously acts as a MT1 and MT2
melatonergic receptors agonist and a 5-HT2C antagonist. As a result,
Valdoxan(R) resynchronises circadian rhythms that are profoundly disrupted in
depressed patients, therefore offering a totally innovative approach to
depression treatment.[6],[7]

Valdoxan(R) was discovered and developed by Servier, France's
leading independent pharmaceutical company. Valdoxan(R) received EU marketing
authorisation in February 2009 and is now available for the treatment of
adult patients with MDD in several countries worldwide.

Notes to Editors

Valdoxan(R) international development programme

The efficacy of Valdoxan(R)in major depressive disorder (MDD)
has been shown in several clinical trials within the international
development programme. This programme documented the unique clinical
signature and the distinctive profile of efficacy of Valdoxan(R) as compared
with placebo, SSRIs and SNRI treatments.

Results of the studies demonstrated that Valdoxan(R):

    - Is more efficacious than conventional antidepressants at
      every step of depression treatment, showing greater patient improvement
      from the first week of treatment, whatever the intensity of depressive
      symptoms[1],[2],[8]

    - Significantly reduces the incidence of relapse in depressive
      patients over the long-term[1]

    - Preserves sexual functioning, is weight neutral and offers a
      favourable tolerability profile, thus contributing to a better
      adherence and remission in depressed patients[5],[9]

    - Is easy to use: one 25 mg tablet taken at bedtime, without
      discontinuation symptoms at the end of treatment[5],[10],[11]

Major depressive disorder (MDD)

MDD - also known as unipolar depression - is a common and
disabling mental health disorder. Globally, MDD is increasing in prevalence,
affecting approximately 121 million people worldwide, yet it remains
under-diagnosed and under-treated.[12] Overall, around 60 million Europeans
currently suffer from some form of depression, with an estimated 33.4 million
of them suffering with severe depression.[13] The WHO reported that
depression was the fourth leading cause of health-related disability, and has
estimated that by 2020 depression will rank second only to heart disease as a
worldwide cause of disability. For many patients, depression is a chronic and
recurrent illness. Nearly a third of patients with MDD are still depressed
after one year, and over 10% remain ill after five years. For those patients
who recover from a depressive episode, over a half will suffer a
recurrence.[14]

References

———————————

[1] Goodwin G et al, Agomelatine Prevents Relapse in Patients
with Major Depressive Disorder Without Evidence of a Discontinuation
Syndromw: A 24-Week Randomized, Double-Blind, Placebo-Controlled Trial. J.
Clin. Psychiatry. 2009;70(8):1128-1137

[2] Stahl SM, Fava M, Trivedi MH, Caputo A, Shah A, Post A. Agomelatine
in the Treatment of Major Depressive Disorder: An 8-Week, Multicenter,
Randomized, Placebo-Controlled Trial J. Clin. Psychiatry. 2010;71(5):616-626

[3] Lemoine P, Guilleminault C, Alvarez E. Improvement in Subjective
Sleep in Major Depressive Disorder With a Novel Antidepressant, Agomelatine:
Randomized, Double-Blind Comparison With Venlafaxine. J. Clin. Psychiatry.
2007;68:1723-1732

[4] Kasper S, Hale A, Lemoine P, Quera Salva MA. Superior efficacy
results of agomelatine in pooled analysis versus SSRI/SNRI. Abstract ECNP
2010

[5] Kennedy S, Rizvi S. Agomelatine in the treatment of major depressive
disorder: potential for clinical effectiveness. CNS Drugs 2010 Review
Article.

[6] Leproult R, Van Ondergergen A, L'Hermite-Balériaux M, Van Cautert E,
Copinschi G. Clin. Endocrinol. 2005;63:298-304

[7] Hale A, Corral R, Mencacci O, Saiz Ruiz J, Severo A, Gentil V.
Superior efficacy of agomelatine vs fluoxetine in severe MDD patients: a
randomised, double-blind study. J. Eur. College of Neuropsychopharmacol.
2009;19(suppl 3):S418

[8] Kasper S et al. Efficacy of the Novel Antidepressant Agomelatine on
the Circadian Rest-Activity Cycle and Depressive and Anxiety Symptoms in
Patients with Major Depressive Disorder: A Randomized, Double-Blind
Comparison with Sertraline. J. Clin. Psychiatry. 2010;71(2):109-120

[9] Kennedy SH, Rizvi S, Fulton K, Rasmussen J. A Double-Blind Comparison
of Sexual Functioning, Antidepressant Efficacy, and Tolerability Between
Agomelatine and Venlafaxine XR. J Clin Psychopharmacol. 2008;28:329-333.

[10] Montgomery SA, Kennedy SH, Burrows GD, Lejoyeux M, Hindmarch I.
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;19:271-280

[11] Valdoxan(R) Summary of Product Characteristics

[12]
www.who.int/mental_health/management/depression/definition/en/
(accessed 22 July 2010)

[13] WHO Europe, Mental health in the WHO European Region Fact
sheet EURO/03/03, 8 September 2003

[14] Prevalence, burden and diagnosis - Chapter One, Page One,
5 April 2007

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