![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 19 of 19. This is the beginning of the thread.
Posted by SLS on April 4, 2005, at 22:41:25
MUNICH, Germany, April 5 /PRNewswire/ --- First Melatonergic Agonist Antidepressant Shows Efficacy and Tolerability
Benefits Over Existing TherapiesValdoxan(R) (agomelatine), the first melatonergic (MT1 and MT2 receptor)
agonist antidepressant, is an innovation in the treatment of depression
with several advantages over existing treatments according to data
presented during the 13th Congress of the Association of European
Psychiatrists. Besides being an effective antidepressant, Valdoxan has
shown particular advantages in improving the often disrupted sleep patterns
of depressed patients, without affecting daytime vigilance."Agomelatine is an interesting and potentially very valuable antidepressant
that is effective in both moderate and severe depression", says Professor
Stuart Montgomery from the Imperial College School of Medicine in London.
"The new agent has a unique mode of action, improves sleep without
affecting daytime alertness and its efficacy is not compromised by sexual
side effects, tolerability problems or discontinuation symptoms."Antidepressant efficacy
The antidepressant efficacy of Valdoxan has been shown at a standard dose
of 25 mg, once daily in the evening, in a dose-ranging study performed in
major depressive disorder (MDD)(1). In this multicentre,
placebo-controlled, dose-ranging study over eight weeks, Valdoxan was shown
to be an effective antidepressant at a dose of 25 mg once daily, by
reducing the initial HAMD score to a similar extent to that of the SSRI
paroxetine. Further studies versus placebo and comparators have confirmed
the efficacy of Valdoxan in adults of all ages, including the severely
depressed and elderly depressed. Results from another clinical trial
presented here in Munich show that Valdoxan has a similar efficacy to the
SNRI venlafaxine.Improvements of disturbed wake-sleep cycles
"The ability to relieve sleep problems without being sedative is a key
advantage for depressed patients who frequently suffer from sleep
disturbances associated with their depression", points out Christian
Guilleminault, MD, from Stanford University Sleep Disorders Clinic, California.Due to its unique pharmacological profile, Valdoxan is the only
antidepressant to have a specific action on circadian rhythms, which are
often imbalanced in depressed patients. By improving disturbed wake-sleep
patterns, according to Dr Guilleminault, Valdoxan is able to relieve sleep
complaints of depressed patients with a favourable impact on daytime vigilance.Tolerability profile
Data presented by Professor Montgomery shows that Valdoxan provides
antidepressant efficacy, but lacks typical antidepressant side effects. The
new agent does not appear to impair sexual function. A study comparing
Valdoxan with venlafaxine showed comparable antidepressant efficacy of both
treatments, but significantly less sexual dysfunction of Valdoxan compared
to the SNRI. In addition, a placebo-controlled, double-blind study
comparing Valdoxan with paroxetine showed that, after one week of treatment
discontinuation, no signs of discontinuation symptoms(i) were seen in the
agomelatine group compared to significant discontinuation symptoms in the
paroxetine group.(2)Valdoxan was discovered and developed by Servier. The drug is currently in
Phase III and a registration dossier for an indication in MDD was recently
submitted to the European Regulatory Agency (EMEA).(i) Discontinuation symptoms occur when treatment with certain
antidepressants (mainly SSRIs and SNRIs) is stopped. They can include
nausea, headache, dizziness, sleep disturbances, anxiety and irritability.References
1. Lôo H, Hale A, D'haenen H. Int Clin Psychopharmacol. 2002; 17:239-247
2. Montgomery SA, Kennedy SH, Burrows GD, Lejoyeux M, Hindmarch I. Int Clin
Psychopharmacol. 2004; 19 :271-280
Posted by SLS on April 4, 2005, at 23:25:36
In reply to agomelatine (Valdoxan) - antidepressant efficacy?, posted by SLS on April 4, 2005, at 22:41:25
I am confused by some of the stuff I read on the Internet regarding the status of agomelatine. Most sites describe this drug as being in phase III, but in phase III where? One website states that agomelatine is in phase III, but that the drug company has not applied to the FDA for approval - only in the European Union.
Does anyone know what's going on with this drug?
- Scott
Posted by jrbecker on April 5, 2005, at 21:46:19
In reply to agomelatine (Valdoxan) - Application to FDA?, posted by SLS on April 4, 2005, at 23:25:36
> I am confused by some of the stuff I read on the Internet regarding the status of agomelatine. Most sites describe this drug as being in phase III, but in phase III where? One website states that agomelatine is in phase III, but that the drug company has not applied to the FDA for approval - only in the European Union.
>
> Does anyone know what's going on with this drug?
>
>
> - ScottI think I am at fault for part of this confusion. On my drug link, I listed Valdoxan as being submitted to the EU for approval. However, what was really the case is that Servier (the pharm company) has submitted the drug for "centralised registration," and not approval yet.
http://www.servier.com/groupe/fruits.asp
Centralised registration is the closest equivalent to the FDA's "Investigational New Drug (IND)" process, which usually takes place sometime during mid-phase clinical trials.
To clarify, it is still in phase III -- and has been so for at least a year and a half now from what I can recall (perhaps longer).
recent press release:
http://www.medicalnewstoday.com/medicalnews.php?newsid=22334Unfortunately, Servier doesn't really provide a lot of updates on what's going with this compound. But I will provide any timely news I can uncover. Apologies for this slip-up. I know quite a few of you were anticipating its release.
JB
Posted by SLS on April 6, 2005, at 6:36:20
In reply to Re: agomelatine (Valdoxan) - Application to FDA? » SLS, posted by jrbecker on April 5, 2005, at 21:46:19
Hi JB.
I am STILL confused!
Has agomelatine been submitted to the U.S. FDA?
Thanks.
- Scott
Posted by jrbecker on April 6, 2005, at 8:52:36
In reply to Re: agomelatine (Valdoxan) - Application to FDA? » jrbecker, posted by SLS on April 6, 2005, at 6:36:20
> Hi JB.
>
> I am STILL confused!
>
> Has agomelatine been submitted to the U.S. FDA?
>
> Thanks.
>
>
> - Scott
>
No.
Posted by rod on April 6, 2005, at 9:54:40
In reply to Re: agomelatine (Valdoxan) - Application to FDA? » SLS, posted by jrbecker on April 6, 2005, at 8:52:36
> > Hi JB.
> >
> > I am STILL confused!
> >
> > Has agomelatine been submitted to the U.S. FDA?
> >
> > Thanks.
> >
> >
> > - Scott
> >
>
>
> No.
>
>About 2 years ago there was a trial in my area (EU).
But havent heard anything about the results.Well, and since its a french drug, it might take a very long time to get approval in the US, because of eceonomic aspects which might be negative for US pharma companies.. Call me a fool to think this, but hey, didnt you rename "french fries" to "freedom fires" ? And there is even a side www the f word and france dot com
Well yes OMG 8-O thats what I have thought about that site...nuff said about evil conspiracy theories.. :-)
oh well
god bless...
whatever
Posted by SLS on April 6, 2005, at 17:04:02
In reply to Re: agomelatine (Valdoxan) - Application to FDA? » SLS, posted by jrbecker on April 6, 2005, at 8:52:36
> > Hi JB.
> >
> > I am STILL confused!
> >
> > Has agomelatine been submitted to the U.S. FDA?
> >
> > Thanks.
> >
> >
> > - Scott
> >
>
>
> No.
This is what I found out via a personal communication:"The dossier has been
submitted to the European Medical Evaluation Agency, EMEA, in April 2005 and
we expect the European Registration in 2006. All future registration
procedures in other countries, including the United States, will depend on
the European registration."
- Scott
Posted by douxmari on April 10, 2006, at 13:34:08
In reply to Re: agomelatine (Valdoxan) - Application to FDA? » SLS, posted by jrbecker on April 5, 2005, at 21:46:19
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."
do you think they can get a quick approval in the US? And how soon can they submit to FDA?
Posted by ravenstorm on April 11, 2006, at 9:47:02
In reply to Re: agomelatine (Valdoxan) - Application to FDA?, posted by douxmari on April 10, 2006, at 13:34:08
Crap!!! I thought this drug was going to be released this year!!!!!!!!!!!!
As for the above signing. I believe that just means that they can now START clinical trials in the U.S. if they want. But who knows when. Crap, Crap, Crap!
Posted by SLS on April 11, 2006, at 10:33:48
In reply to Re: agomelatine (Valdoxan) - Application to FDA?, posted by ravenstorm on April 11, 2006, at 9:47:02
> Crap!!! I thought this drug was going to be released this year!!!!!!!!!!!!
>
> As for the above signing. I believe that just means that they can now START clinical trials in the U.S. if they want. But who knows when. Crap, Crap, Crap!
Agomelatine (Valdoxan) should become available soon in Europe if it isn't already.
- Scott
Posted by ravenstorm on April 11, 2006, at 10:47:13
In reply to Re: agomelatine (Valdoxan) - Application to FDA? » SLS, posted by jrbecker on April 5, 2005, at 21:46:19
OK, confusion continues then, because that is not what I got out of JRBEckers post:
"However, what was really the case is that Servier (the pharm company) has submitted the drug for "centralised registration," and not approval yet.
http://www.servier.com/groupe/fruits.asp
Centralised registration is the closest equivalent to the FDA's "Investigational New Drug (IND)" process, which usually takes place sometime during mid-phase clinical trials.
To clarify, it is still in phase III -- "
To me, that sounds like they are still in phase III trials in Europe, because I know from contacting the company many months ago, that they were not doing trials in the U.S. yet and didn't know when or if they would be.
I had thought they had already completed trials and submitted for approval in Europe, but that is not how I am reading JRB's latest post.
I think I will have to concur with you when I say: I am still confused!!
Poor JRB. Trying to make complicated information readily available to the depressed mind can't be easy. I really thank you for your updates on new drugs!
Posted by tizza on April 11, 2006, at 19:47:42
In reply to Re: agomelatine (Valdoxan) - Application to FDA?, posted by ravenstorm on April 11, 2006, at 10:47:13
I looked into this a couple of months ago and from whay I can gather it was only phase 3 in the EU. There isn't very much info around about it. Probably because if it can do what they're saying it can, it will blow all other AD's out of the water. It's all very interesting. Maybe the want to keep it reasonably quite until they get it on the market. Who knows, Paul
Posted by rod on April 11, 2006, at 20:16:46
In reply to Re: agomelatine (Valdoxan) - Application to FDA?, posted by ravenstorm on April 11, 2006, at 10:47:13
> To clarify, it is still in phase III -- "
>
> To me, that sounds like they are still in phase III trials in Europe, because I know from contacting the company many months ago, that they were not doing trials in the U.S. yet and didn'tExactly. And approval in europe (if the trials are sucessful) will be around the end of 2006, beginning of 2007.....
Posted by ravenstorm on April 11, 2006, at 22:08:41
In reply to Re: agomelatine (Valdoxan) - Application to FDA?, posted by rod on April 11, 2006, at 20:16:46
Well they must approve things a lot faster in Europe then. Because if something was still in phase III trials in April in the U.S. there is no way in hell it would suddently be approved by the end of the same year.
Posted by jrbecker on April 11, 2006, at 23:48:50
In reply to Re: agomelatine (Valdoxan) - Application to FDA?, posted by ravenstorm on April 11, 2006, at 22:08:41
To try to clear up someof the confusion, I thought I'd offer a little more info about the current situation.
The good news is that the recent press release about Novartis buying the U.S. licensing rights for Agomelatine means that European approval is quite optimistic.
Bad news...here in the U.S., Novartis will have to do further Phase III (and possible Phase II) trials to pass specific FDA standards before approval. Novartis should be revealing a clinical trial design sometime within the next few months that will hopefully highlight an eventual application timeframe.
Back the European picture, the drug was submitted to the European Medicines Evaluation Agency (EMEA) for review in April 05. Although the EMEA review timeframe can vary considerably, the current average response time this year is approximately 12months....meaning we could even see a response later this month, but possibly not til summer or later. BUT, the EMEA response doesn't mean final market approval. In reviewing drug applications, the EMEA issues either a "positive" or a "negative" opinion. If it's positive, then the EMEA then forwards on the application to the European Commission (EC) for official approval. This is known as the post-opinion phase, which takes approx 40-50 days for filing. Then, the EC decision process actually takes 50-70 days. So, all this means that even if the EMEA gives a positive opinion later this month (April), the EC probably won't approve it officially until the earliest, August. Lastly, the pharm company won't probably get the product on the market until at least 1-2 months later. And that's in the swiftest circumstances. I think fall or even winter 2006 is just as likely.
For more info on Average European average drug review timelines, see below.
European Drug Approval Timeframes:
2005 Average timeline (preliminary results as of MARCH mtg, out of 28 reviewed products)
Assessment phase: 201 days
*Clock-stop: 161 days
Post-opinion phase: 46 days (2004 avg)
Decision process: 56 days (2004 avg)=464 days (15 months)
2004 Average timelines:
Assessment phase: 210 days
*Clock-stop: 123 days
Post-opinion phase: 46 days
Decision process: 56 days= 435 days (14.5 months)
Last 3 year’s Average timelines:
Assessment phase: 208.3 days
*Clock-stop: 214.3 days
Post-opinion phase: 40.6 days
Decision process: 66.3 days= 530 days (17.6 months)
*the clock is stopped during the review process for the company to address issues brought up during scientific review.
Posted by ravenstorm on April 12, 2006, at 8:45:25
In reply to Re: agomelatine (Valdoxan) - FDA? not quite yet, posted by jrbecker on April 11, 2006, at 23:48:50
OK, I'm very clear now on the what is going on.
Thanks JRB!
P.S. Have clinical trials been going on in Canada?
Posted by Larry C on April 18, 2006, at 20:20:11
In reply to Re: agomelatine (Valdoxan) - FDA? not quite yet, posted by ravenstorm on April 12, 2006, at 8:45:25
Yes, it was definitely tested in Canada.
I think they actaully had the trials at Sunnybrook Hospital in Toronto.
Somehow, I don't think that we'll be one of the first countries to get it.
> OK, I'm very clear now on the what is going on.
>
> Thanks JRB!
>
> P.S. Have clinical trials been going on in Canada?
Posted by HelenER on July 7, 2006, at 7:37:24
In reply to Re: agomelatine (Valdoxan) - FDA? not quite yet, posted by Larry C on April 18, 2006, at 20:20:11
I was interested to read these posts and not sure if it is still active, but one thing that I found curious was that agomelatine seems to have a short patent, possibly expiring before it ever reaches the market in the US, so why would Novartis bother to invest in it?
Posted by Larry C on September 4, 2006, at 22:06:59
In reply to Re: agomelatine (Valdoxan) - Application to FDA?, posted by SLS on April 11, 2006, at 10:33:48
Bad news, Valdoxan's application was rejected by the European Union on August 14, 2006.
The EU said that Servier didn't prove Valdoxan's long-term effectiveness.
The short-term studies did show benefit.
The EU was not concerned about Valdoxan's side-effects.
I don't know how this will affect Servier's deal with Novartis for North Ameican distribution.
I wouldn't hold my breath waiting for this to be marketed in North America.
Oh well.
> > Crap!!! I thought this drug was going to be released this year!!!!!!!!!!!!
> >
> > As for the above signing. I believe that just means that they can now START clinical trials in the U.S. if they want. But who knows when. Crap, Crap, Crap!
>
>
> Agomelatine (Valdoxan) should become available soon in Europe if it isn't already.
>
>
> - Scott
This is the end of the thread.
Psycho-Babble Medication | Extras | FAQ
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.org
Script revised: February 4, 2008
URL: http://www.dr-bob.org/cgi-bin/pb/mget.pl
Copyright 2006-17 Robert Hsiung.
Owned and operated by Dr. Bob LLC and not the University of Chicago.