Valdoxan(R), the First Melatonergic Antidepressant, Confirms its Efficacy in Preventing Relapse Whatever the Severity of the Depression

Vienna, Austria (ots/PRNewswire) - Valdoxan(R) (agomelatine), the
first melatonergic antidepressant, is an effective, long-term
treatment for Major Depressive Disorder (MDD) according to new data
presented today at the European College of Neurospsychopharmacology
(ECNP) annual congress. The new international study showed Valdoxan's
efficacy in preventing relapse in out-patients with MDD over
six-months, irrespective of the severity of depression(1).

"The short term efficacy of this novel antidepressant has already
been demonstrated in several clinical studies", points out study
investigator Professor Guy Goodwin from the Department of Psychiatry,
University of Oxford, UK. "This new study demonstrated the long-term
efficacy of Valdoxan in the prevention of depressive relapses, after
an initial response to the drug, over a treatment period of six
months. The results show that Valdoxan is a promising therapeutic
agent for the short-and-long-term management of MDD, which offers
remission to our depressed patients with very few adverse effects".

The multicentre, randomised, double-blind study involved nearly
500 (n=492) patients with recurrent MDD according to the DSM-IV
classification. The primary outcome of the study was time to relapse
(relapse defined as HAM-D17 score ³ 16 or any withdrawal for lack of
efficacy according to the investigator's opinion during the
randomised period).

Valdoxan: significantly lower relapse rate

Overall, Valdoxan was associated with a significantly lower
relapse rate compared to placebo (p=0.0001). Nearly half of all
patients who received placebo relapsed (46.6%) compared to just over
fifth of patients who received Valdoxan (21.7%) over a six month
treatment period, representing a 54% reduction of the risk of relapse
for patients treated with Valdoxan. These results demonstrating the
long-term antidepressant efficacy of Valdoxan were further confirmed
in the more severely depressed subpopulation of the study. In
patients with a baseline HAM-D17 score of greater than or equal to
25, Valdoxan was associated with a significantly fewer cumulative
relapses (22.7%) than placebo (50.4%) over six months.
Interestingly, the low number of early relapses (up to 6-8 weeks
after randomisation) reported by patients switched from Valdoxan to
placebo is an additional proof of absence of discontinuation
symptoms when stopping Valdoxan treatment. Valdoxan treatment was
found to be well tolerated with the rate of treatment-emergent
adverse events similar in patients receiving active treatment and
placebo.

Valdoxan: efficacy in severely depressed patients

The antidepressant properties of Valdoxan have been demonstrated
in several clinical trials, including large-scale phase III studies
either versus placebo or other antidepressants(2-6). Efficacy has
been shown to be superior in comparison to placebo and at least equal
in comparison to selective serotonin reuptake inhibitors (SSRIs) and
selective noradrenaline reuptake inhibitors (SNRIs), against which
Valdoxan showed favorable trends in terms of response and remission
rates. Valdoxan also demonstrated to be effective across clinical
trials, whatever the severity of depression including in the subgroup
of severely depressed patients. Results of placebo controlled studies
showed that the greater the severity of depression, the greater the
treatment efficacy of Valdoxan.

A reduction in sleep disruption, a core symptom of depression and
a common problem in people with depression, without any sedation
during the daytime, is one of the clinical benefits of Valdoxan
treatment(5,7).

An innovative approach to the treatment of depression

Binding studies have shown that Valdoxan, the first melatonergic
antidepressant, interacts with both melatonergic (agonist) receptors
(MT1 and MT2), and with 5-HT2C (antagonist) receptors.8 The
antidepressant efficacy of Valdoxan involves joint actions on these
receptors, possibly interacting synergistically. Valdoxan
resynchronizes altered circadian rhythms of depressed patients, thus
retaining antidepressant efficacy without the typical side effects
such as sexual dysfunction(8,9) and drug discontinuation symptoms
commonly seen with other antidepressants (SSRIs and SNRIs). Overall,
Valdoxan possesses a pharmacological profile entirely distinct from
SNRIs and SSRIs, making it an innovation and a significant advance in
the treatment of depression.

Valdoxan was discovered and developed by Servier, France's leading
independent pharmaceutical company. Novartis acquired exclusive
rights to further develop and market agomelatine in the United States
and several other countries. Servier retained the rights to develop
and market the product in the rest of the world.

References

(1) G Goodwin, F Rouillon, R Emsley. Long-term efficacy of
agomelatine, a novel antidepressant, in the prevention of relapse in
out-patients with Major Depressive Disorder. ECNP presentation 2007

(2) Lôo H, Hale A & D'Haenen H. 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: 239-247.

(3) Kennedy SH, Emsley RA. Placebo-controlled trial of agomelatine
in the treatment of major depressive disorder. Eur
Neuropsychopharmacol 2006;16: 93-100.

(4) Olie J-P, and Kasper Efficacy of agomelatine, a MT1/MT2
receptor agonist with 5-HT2C antagonistic properties, in major
depressive disorder. Int J Neuropsychopharmacol 2007 E-pub ahead of
print

(5) Lemoine P, Guilleminault C and Alvarez E Improvement of
subjective sleep in Major depressive disorder with a novel
antidepressant agomelatine: randomized, double blind comparison with
venlafaxine. J Clin Psychiatry. In Press

(6) S.H.Kennedy, C. Guilleminault. Antidepressant efficacy of
agomelatine 25-50 mg versus venlafaxine 75-150 mg: two randomized,
double blind studies. Eur Neuropsychopharmacol 2006, 16, S 319

(7) MA Quera-Salva, Vanier B, Laredo J, Chapotot F, Moulin C,
Lofaso F and Guilleminault C. Major Depressive Disorder, Sleep EEG
and Agomelatine: an open label study. Int J Neuropsychopharmacol
2007, Epub ahead of print

(8) M. Hamon, MJ Millan. Agomelatine, a novel pharmacological
approach to treating depression. European College of
Neuropsychopharmacology (ECNP) 2006. Eur Neuropsychopharmacol 2006,
16, S 337

(9) S.H. Kennedy. Favorable sexual profile of agomelatine in
depressed patients Eur Neuropsychopharmacol 2006, 16, S 319

ots Originaltext: Servier
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Contact:
For further information, please contact: Moira Gitsham, Tonic Life
Communications, +33-5-46-00-08-20, moira.gitsham@toniclc.com; Leah
Baldwin, Tonic Life Communications, +44-207-798-9923,
leah.baldwin@toniclc.com