![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 3 to 27 of 27. Go back in thread:
Posted by chemist on May 11, 2005, at 21:31:06
In reply to History of emsam as I know it, posted by yldouglas on May 11, 2005, at 19:09:02
hello there, chemist here...this is an interesting post and topic...i have a comment or two and some questions, delineated by asterisks....all the best, chemist
> I've been following the development of the emsam patch for several years as I am at the end of the line for antidepressants (Wellbutrin for 5 years now)
>
> Two pharm co's (Watson and Mylan) formed a joint venture, Somerset, which handles L-deprenyl for Parkinson's disease patients. L-deprenyl is selegiline which is the active ingredient in the EmSam Patch. L-deprenyl is a MAO-B inhibitor under doses of 15-20 mg. Once you go over that dosage, it becomes a MAO-A inhibitor, which has deadly side effects (called the tyramine reaction), which is a reaction to certain foods and medications such as aged cheese, wine, and many others. But that reaction all happens in the "gut" or digestive system.
>
> L-deprenyl works on the dopamine receptors (Wellbutrin is the only anti-depressant that does anything significant with dopamine, which is why they slightly changed the formulation, made a new pill, called it Zyban and marketed it for people trying to quit smoking as nicotine stimulates the dopamine system. This is why I can smoke whenever I want and stop cold turkey and basically don't notice a thing. sorry for the tangent) Anyway, someone, somewhere discovered that at higher doses, L-deprenyl works great as an anti-depressant.
>
> One of the two companies has developed transdermal patch systems that can handle larger molecules than those already on the market. They got together with the L-deprenyl people and figured out that if you could make L-deprenyl into a transdermal patch where the medication would go directly into the blood stream, bypassing the digestive system, you could deliver higher doses without the danger of the tyramine reaction.
>
> They started testing and had amazing results (if we can believe them and I actually do) with no tyramine reactions occurring. They received approval from the FDA in February 2004 but wanted Somerset to include a warning on the tyramine effect. The company strongly feels they have the evidence that this is not necessary and know if they have to put that warning out there it will adversely affect sales. So they've been struggling with the FDA to leave that warning off the labeling.
>
**** actually, the letter was ``approvable,'' and not ``approval:'' the letter to which you refer was following a ``non-approvable'' letter delivered to Somerset and Watson 1Q2002. the MAO-A/B switch that you mention is a mystery: the drug is an MAO-B inhibitor as low doses, and a dopamine uptake inhibitor at high doses. the ``someone, somewhere'' discovery that ``high doses'' of the drug working as an antidepressant are over 30 years old, as is the drug (1962, actually). ****> The good news is Somerset has reached an agreement with Bristol Myers Squib to be the distributor for the patch. The hope is BMS will be able to use its clout to resolve the labeling issue with the FDA.
>
> This is making me crazier than I already am. I have wanted to try this patch for four years since I first read about it and really thought it would be available the first half of 2004. I can't believe another year has passed and it is still being kept captive by the FDA. I'm hoping BMS can finally make it happen. I have talked directly to people in the investment departments of both companies (no one else would respond), which is how I know all this info. I will try to find some time to do some more research and try to get an update. If I succeed I will come back and post the latest. I hope this helps any and all of you looking for relief.
>
> Aloha,
>
> yldouglas.
>
**** could you be so kind as to pass along the names and contact information for the people to whom you have had contact at both BMS and Somerset? you can enable babblemail if you wish, although in the interest of furthering the effort, perhaps a public posting is better - your choice, of course...but i am very eager to talk to them and, incidentally, to you as well...all the best, chemist ****
Posted by chemist on May 12, 2005, at 11:56:42
In reply to Re: History of emsam as I know it » yldouglas, posted by Chairman_MAO on May 11, 2005, at 20:16:03
hello there, chemist here...apparently we were penning responses at the same time, and i did not come across your take until now....big pharma does, as you assert, have a very big hand in the labeling fiasco in this case, although as emsam is not approved the fiasco is more pointedly directed at the capsule and tablet formulations (brand name Eldepryl) marketed by Somerset...this is all academic, however, as it is not just slightly entertaining that a new PB post is presenting nothing more than an advertisement for emsam: it is misleading and worse, some readers will actually believe what is stated.
having an intact relationship with a pharmaceutical company, i have (perhaps) a bit of an eye for nonsense given the one-way, lifelong, and ironclad non-disclosure and non-competition paperwork that places all liability on the employee should they divulge any information that could lead to a competitor gaining a financial edge.
i am not allowed to discuss the names and positions of the people i have worked with and any specifics beyond what one can glean from their website, and this is the tip of the iceberg. i can assure you that the money handlers at BMS and any other well-capitalized company are just as ignorant of what is happening in the labs as the scientists are about finances.
the securities fraud and industrial espionage aspects are real; the story related in this thread is an impossibility or a matter that should be pursued by the companies, the SEC, and the FDA (my request for communication is to increase my net worth, as i want access to the inside information!), and is (from a scientific point) quite inaccurate.
further, although the search engine is hardly known to turn up the proper goods at the outset, a simple google search will reveal all the information presented in the post, with the exception that the details posted at mylan, watson, bms, and somerset appear to contain actual and accurate information.
i suggest a jaunt to the FDA site, particularly
http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm
which is easily reached (CDER Archives) from www.fda.gov. there, you can actually locate the drug Eldepryl, and learn about the NDA/ANDA/BLA business (and other meaningful acronyms), and make an informed decision.
once one arrives at the governing body for drug regulation in the u.s., you can download the PDF dated (action date, meaning date of action of - here - approval of the labeling change) august 6, 1997. it is free for the downloading, and one can see - if they have not bothered to do so yet are quick to point a finger at the big pharmas (Somerset is hardly one of them) - that the correspondence chain clearly shows that Somerset dragged their feet for 7.5 months, followed by another 8 months to include very bland, sparse, and important wording requested by the FDA in the interest of better informing physicians and patients.
first and foremost, the emsam patch is not approved, nor is the approvable letter an easy find - the best i can determine is that through the entire FDA web domain, a search with the word emsam yielded 11 hits, and several appear to concern canine tooth heath (yes, really).
eldepryl - in the labeling revision documents - is treated very fairly, if one takes the time to read the official, scanned, and posted letters and data. i refer you to page 7 of the document, where an adverse interaction between selegiline and ephedrine; and two hypertensive ``cheese reactions'' at 5 mg p.o. b.i.d. selegeline taken with tyramine-rich foods had been reported.
the FDA requested that Somerset make a labeling change to indicate that there is a risk of such reactions on may 15, 1996. Somerset took their time and replied to the FDA on January 2, 1997 that the changes were made in the Warnings, Information for Patients, and Precautions sections of the labeling information. the FDA sent two letters and instigated one teleconference over the 7.5 months it took the drug company to add (literally) a few sentences to a package insert. a miscommunication (the words of the FDA) was blamed for Somerset not including this information in the Clinical Pharmacology section - a very nice gesture on the part of the FDA, by the way - and the FDA requested that Somerset complete the challenging task of penning less than one paragraph indicating that 3 people who were arguably pushing the envelope are the sum total of the cohort who have experienced serious complications. 3 people - one who took ephedrine and two who might have been predisposed to any hint of a ``cheese reaction'' - is not a number that is likely to have impacted sales.
the wording in the new label changes - which was apparently very difficult for Somerset to implement, and even then, the ``miscommunication'' caused a further 8-month delay - is strongly worded in regards to the small number of patients (3) reporting adverse effects, that reactions such as these are rare at low doses but can become more of a risk with higher doses, and that 3 cases are not conclusive or indicative of the safety of the medication yet Somerset feels it is prudent to mention it anyway (this is, of course, not true, as the process took an excruciating 15 months: the FDA insisted).
so, do indeed blame the pharma, who would just as soon not mention any adverse effects at all, if their sluggish response to a directive that is in the best interest of the health of the patients as well as in the self-interest of diverting liability from Somerset is any indication...
the next question is: what would one prefer? that a request made to add a watered-down and cautious addition to a label not be honored, or that the manufacturer of the medication reveal even a small number of adverse effects - actually, an almost unheard of small number of adverse effects - that are in the best interest of those taking the medication?
and the tyramine (or some other) interaction is bound to occur in at least one patient: common sense and for many of us personal experience indicate that even the ``safest'' medication will adversely effect at least a very small number of patients.
the claim that only persons involved in the financial sections of the pharmaceutical companies have provided information concerning emsam - especially information way out of their collective area of expertise and to a stranger, no less, who contacted these parties and found that they were willing to hand out company secrets - is beyond absurd. thus, i eagerly await contact from this poster so i can better position myself with my broker for the day that the letter of approval comes through - if it comes through.
yes, big pharma was in fact behind this fiasco, and given the poor record Somerset has shown in the instance detailed above, why would any person who is aware of the 15 months they took to add information that is useful to patients, doctors, and the company even begin to consider the next offering?
*** note: i am not associated with a competing interest of any of the companies involved in marketing the drug(s) discussed herein. my comments concerning inside information are in jest (those pertaining to building my cash reserves, the rest are not in jest) and i do not have investments in any of the companies mentioned here. my comments are speculative, intended to inform any person who cares to read or heed what i have written, and point out - as chairman MAO has - that the pharmas are indeed to blame in this case, as it is more than clear that the FDA was taking the high road while Somerset did little or nothing to disclose what was requested. ****
all the best, chemist
> I am thoroughly convinced that big pharma has its hand in this labelling fiasco. If there's no tyramine restriction, EmSam will utterly decimate most antidepressants on the market today; it simply would feel much better for many people than SSRIs, etc. It's simply a better drug that produces a more savory effect. There would be virtually no reason that anyone who could tolerate activating meds, such as Wellbutrin, would want to take it when they could take EmSam.
>
> With the tyramine restriction, they'll be able to pigeonhole it into "MAOI oblivion" which orthodox year-2005 psychiatry seems to consider more dangerous than swimming in the river styx.
>
> "Babylon system is the vampire, sucking the blood of the sufferers."
>
> --Bob Marley
Posted by Chairman_MAO on May 12, 2005, at 20:43:54
In reply to .... » Chairman_MAO, posted by chemist on May 12, 2005, at 11:56:42
Oh, I certainly never claimed that Somerset was any different from any other pharmaceutical company; I always thought their pricing for Eldepryl was usurous. I am also confused; was most of your post re: my post actually in response to the original poster, or what I wrote?
What I was getting at specifically was labelling for the patch, not the tabs/caps. Certainly there should be SOME kind of warning about the POSSIBILITY of a tyramine reaction, but as I understand it the FDA wanted to put labelling on it indicating a tyramine RESTRICTION was necessary, a la irreversible, nonselective MAOIs.
Am I correct about this? I was kinda confused about what you were saying specifically to me or in response to what I wrote, and what you were writing to someone else/the board on a whole. :)
Posted by pseudonym on May 12, 2005, at 21:55:33
In reply to History of emsam as I know it, posted by yldouglas on May 11, 2005, at 19:09:02
Also, I checked the patent number on the selegiline patch ( # 4861800) , and it was filed back in 1987.
Only ~20 years to get this to market?For those who care, the patent described a number of methods of administration, including a Polyethylene glycol ointment, a cream base, and the transdermal patch everyone is so excited about, in which selegiline is disolved in mineral oil and allowed to disolved through polypropylene into the skin.
Posted by Larry Hoover on May 12, 2005, at 22:56:00
In reply to .... » Chairman_MAO, posted by chemist on May 12, 2005, at 11:56:42
http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm
>
> which is easily reached (CDER Archives) from www.fda.gov. there, you can actually locate the drug Eldepryl, and learn about the NDA/ANDA/BLA business (and other meaningful acronyms), and make an informed decision.I see all kinds of ANDA applications approved in the period of 96-98. Obviously, the stuff is off patent. Does the delivery system make Emsam a new drug?
If I'm not mistaken, the transdermal route is supposed to avoid first-pass metabolism, and thus avoid the whole tyramine thing (i.e. the protective enzymes in the gut are spared, leaving them "on guard" against ingested tyramine). Is it that this mechanism isn't proved? Or that nobody wants to stick their neck out in this particular legal/political climate? It's not a medical issue, is it? I don't think so.
And so, I leave loose ends, and off to bed.
Lar
Posted by smith562 on May 13, 2005, at 7:05:19
In reply to Re: .... » chemist, posted by Chairman_MAO on May 12, 2005, at 20:43:54
Hey Everyone,
A bit off the topic of the patch, but I have found selegiline 10mg to work great for my depression (this added into zoloft, klonopin, lithium). I haven't posted much because I am back into life. Out with friends, buy some new clothes, going to the gym ... back to a normal existance! Life is better now.
Smith
Posted by chemist on May 14, 2005, at 5:47:38
In reply to Re: .... » chemist, posted by Chairman_MAO on May 12, 2005, at 20:43:54
hello there, apologies for the delay in getting back...my post was in response - if that is the correct word - to what the orignial post claimed and/or promoted...your post (specifically) was, unfortunately, the victim of my almost invariant habit of simply replying to a thread and clicking both the ``notify me..'' and ``include name of previous poster'' buttons: your post as i note does point to the company, and no others, as being the entity to point a finger, should one feel the need.
the issue of the labeling remains a mystery to me, and is not something that is available - in my search - through the regulatory channels that emanate from the FDA via the web. and i was addressing the mysterious and non-communicative recently-enrolled PB poster who initiated the thread, in a general sense: i also admit to being more than a little guilty of being biased towards addressing with vigor posts such as the original.
whether or not the FDA, another party (public or private), or other force is involved with the marketing of this drug for a particular reason is not a question i can answer, nor does it appear to be easily (if at all) found within the resources to be disseminated to the public via the government or (and i did check, only to uncover press releases and not much else) the companies involved in making, marketing, distributing, and profiting from emsam if/when it makes it to market.
that selegiline - regardless of how it is administered - is a type B MAO inhibitor in the 5 to 20 mg dosing regime, and a selective dopamine uptake inhibitor in higher doses in not subject to much more debate, in my opinion. the route of delivery - transdermal - should bypass the gastic circuitry as reported, within reason. the literature contains studies that indicate that the tyramine reaction(s) are scant or rare: however, these reactions have occurred.
the original post leans more than a little in the direction of ``a wonderful drug is being held from the needy and because i can only glean information from the financial departments of the pharmaceutical companies involved - and not the scientific arms - there is obviously something amiss.''
unfortunately, the first response to the post - from Chairman_MAO - includes the phrase that ``I am utterly convinced that big pharma has its hand in this labelling fiasco,'' and is followed by the prediction that *if* EmSam is introduced to the marketplace without the labeling which would otherwise send the drug into ``MAOI oblivion,'' then EmSam will ``utterly decimate most antidepressants on the market today.'' the drugs to be decimated are named as ``SSRIs, etc.'' the conclusion that large pharmaceutical companies that produce any antidepressant - and market it - are not uninvolved in the delay of EmSam to market is unavoidable, whether meant that way or not. singling out Wellbutrin as a medication for which there would be no use to those who cannot take it - because of overactivation - if EmSam was available (a ``better drug that produces a more savory effect'') does bolster the original post.
there is no evidence that the drug will/will not decimate the SSRI (or other) antidepressant market, nor is there any evidence to support or prove false any claim a distribution partership with BMS is anything other that a business arrangement. the original poster claims that BMS is involved for reasons that include the perceived might that it has in pushing drugs to market which are otherwise held in limbo at the FDA: while one can easily and correctly note that i cannot prove that this is not the case, i can - as well as any other person - easily prove that the employees of the pharmaceutical companies (specifically, those in the ``investment'' portions) are not disclosing inside information. i made some calls of my own, and as a person with no ties to any of the numerous parties involved with EmSam, i failed to reach the sections of Mylan, Somerset, Watson, and BMS where a person in the ``investment department'' - a fictional designation, by the way, at all companies involved - would provide to me information concerning exactly why there was a delay in EmSam being marketed and, further, the role of including BMS for reasons other than a large distribution/marketing partner.
all the best, chemist
> Oh, I certainly never claimed that Somerset was any different from any other pharmaceutical company; I always thought their pricing for Eldepryl was usurous. I am also confused; was most of your post re: my post actually in response to the original poster, or what I wrote?
>
> What I was getting at specifically was labelling for the patch, not the tabs/caps. Certainly there should be SOME kind of warning about the POSSIBILITY of a tyramine reaction, but as I understand it the FDA wanted to put labelling on it indicating a tyramine RESTRICTION was necessary, a la irreversible, nonselective MAOIs.
>
> Am I correct about this? I was kinda confused about what you were saying specifically to me or in response to what I wrote, and what you were writing to someone else/the board on a whole. :)
Posted by chemist on May 14, 2005, at 5:57:36
In reply to Re: ....patent expired » chemist, posted by Larry Hoover on May 12, 2005, at 22:56:00
> http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm
> >
> > which is easily reached (CDER Archives) from www.fda.gov. there, you can actually locate the drug Eldepryl, and learn about the NDA/ANDA/BLA business (and other meaningful acronyms), and make an informed decision.
>
> I see all kinds of ANDA applications approved in the period of 96-98. Obviously, the stuff is off patent. Does the delivery system make Emsam a new drug?
>
> If I'm not mistaken, the transdermal route is supposed to avoid first-pass metabolism, and thus avoid the whole tyramine thing (i.e. the protective enzymes in the gut are spared, leaving them "on guard" against ingested tyramine). Is it that this mechanism isn't proved? Or that nobody wants to stick their neck out in this particular legal/political climate? It's not a medical issue, is it? I don't think so.
>
> And so, I leave loose ends, and off to bed.
>
> Larhi larry et al...the regulatory framework in place at the FDA does allow a company to secure a patent - exclusive, at that - for a drug that is shown to be effective in treating conditions for which it was not orignally approved, yes: hence, the prozac/serafem business, and the wellbutrin/zyban business. this list goes on and on. the delivery mechanism does not warrant an NDA or IND; the antidepressant status vs. the antiparkinsonian does. prozac (AD) is under patent as Serafem which is indicated in treating something known as PMDD; wellbutrin is an AD, while zyban is indicated for smoking cessation.....yours, c
Posted by chemist on May 14, 2005, at 6:18:35
In reply to Re: ....patent expired » chemist, posted by Larry Hoover on May 12, 2005, at 22:56:00
...and i did not answer (in my opinion) your query/rhetorical question/other about this being an issue other than medical: i think it isn't, for the reasons you state and in light of the non-zero chance that an adverse reaction might occur a la the tyramine sort....yours, c
Posted by Larry Hoover on May 14, 2005, at 12:39:29
In reply to Re: ....patent expired » Larry Hoover, posted by chemist on May 14, 2005, at 5:57:36
> hi larry et al...the regulatory framework in place at the FDA does allow a company to secure a patent - exclusive, at that - for a drug that is shown to be effective in treating conditions for which it was not orignally approved, yes: hence, the prozac/serafem business, and the wellbutrin/zyban business. this list goes on and on. the delivery mechanism does not warrant an NDA or IND; the antidepressant status vs. the antiparkinsonian does. prozac (AD) is under patent as Serafem which is indicated in treating something known as PMDD; wellbutrin is an AD, while zyban is indicated for smoking cessation.....yours, c
Indeed, and what I found frustrating, is that with all the commentary vis a vis Emsam vs. Eldepryl, I can find no supplemental application.
Serafem and Prozac have the same NDA code number, but appended is a supplemental application code, and so on.
I cannot find an original NDA for Eldepryl (or any other product form of selegiline) that has a supplemental indication application pending, or correspondence about such a thing.
I appreciate that such correspondence is probably confidential, at this stage in the game, but if you search on the VNS device application, you see all kinds of "intermediate" correspondence, leading towards the (hoped for) approval. Nothing similar for Emsam, that I can find.
Lar
Posted by chemist on May 15, 2005, at 2:44:48
In reply to Re: ....patent expired » chemist, posted by Larry Hoover on May 14, 2005, at 12:39:29
> > hi larry et al...the regulatory framework in place at the FDA does allow a company to secure a patent - exclusive, at that - for a drug that is shown to be effective in treating conditions for which it was not orignally approved, yes: hence, the prozac/serafem business, and the wellbutrin/zyban business. this list goes on and on. the delivery mechanism does not warrant an NDA or IND; the antidepressant status vs. the antiparkinsonian does. prozac (AD) is under patent as Serafem which is indicated in treating something known as PMDD; wellbutrin is an AD, while zyban is indicated for smoking cessation.....yours, c
>
> Indeed, and what I found frustrating, is that with all the commentary vis a vis Emsam vs. Eldepryl, I can find no supplemental application.
>
> Serafem and Prozac have the same NDA code number, but appended is a supplemental application code, and so on.
>
> I cannot find an original NDA for Eldepryl (or any other product form of selegiline) that has a supplemental indication application pending, or correspondence about such a thing.
>
> I appreciate that such correspondence is probably confidential, at this stage in the game, but if you search on the VNS device application, you see all kinds of "intermediate" correspondence, leading towards the (hoped for) approval. Nothing similar for Emsam, that I can find.
>
> Lar
>hi larry, i posted a windy reply to this hours ago, yet i must have ditched it...if you go to the 2003 archives of CDER, you will find the NDA # for Eldepryl, and in the 1997 archive, mention of - but no links that work (for me) - three (3) supplemental notations, likely the labeling and other changes. it appears that emsam is a ghost or a well-kept secret. i am not aware of any reason why sundry letters would be held by the FDA/other...the closest thought i ahve - not borned by limited experience - is that if a drug is about to fill the shelves, then a media blackout from the gov't is warranted as it might fuel trading in financial markets. just a guess, and the NDA # for Eldepryl is 020647, approved 05/15/1996, labeling revision 08/06/1997, and control supplement 02/15/2001. the NDA went to somerset, and therapeutic equivs for aaipharma, clonmel, and torpharm are given, although the reference - somerset's 5 mg selegiline HCl oral tablet - is TE == AB (unusual), and the generics are AB (par for the course...)....a mystery indeed...yours, c
Posted by Larry Hoover on May 15, 2005, at 9:06:09
In reply to Re: ....patent expired » Larry Hoover, posted by chemist on May 15, 2005, at 2:44:48
> hi larry, i posted a windy reply to this hours ago, yet i must have ditched it...
Doncha HATE that? The second time around is never as good.
> if you go to the 2003 archives of CDER, you will find the NDA # for Eldepryl, and in the 1997 archive, mention of - but no links that work (for me) - three (3) supplemental notations, likely the labeling and other changes. it appears that emsam is a ghost or a well-kept secret.
Right. Exactly. It's approved as anti-Parkinsonian.
> i am not aware of any reason why sundry letters would be held by the FDA/other...the closest thought i ahve - not borned by limited experience - is that if a drug is about to fill the shelves, then a media blackout from the gov't is warranted as it might fuel trading in financial markets. just a guess, and the NDA # for Eldepryl is 020647, approved 05/15/1996, labeling revision 08/06/1997, and control supplement 02/15/2001.
But, Somerset had another NDA, for the same drug, under 019334, which was simply withdrawn. Approved in 1989, so it's not expired yet.
> the NDA went to somerset, and therapeutic equivs for aaipharma, clonmel, and torpharm are given, although the reference - somerset's 5 mg selegiline HCl oral tablet - is TE == AB (unusual), and the generics are AB (par for the course...)....a mystery indeed...yours, c
So, I'm baffled. How does one get a therapeutic equivalent on a newly approved med? Only if there is no patent, right?
And, it's quite clear that the FDA is hanging tough on the two reported cases of tyramine reaction, on 5 mg b.i.d. *oral* selegiline.
No selegiline trial comes up at http://www.clinicaltrials.gov/
Already done?I checked the orange book listing for selegiline. There are 13 approvals, and the Somerset and Apotex products have been used by others as the comparator for substantial equivalency. There are no existing patents or exclusivity limits for selegiline.
Anyway. Hmmmphhh.
Lar
Posted by chemist on May 15, 2005, at 23:39:59
In reply to Re: ....patent expired » chemist, posted by Larry Hoover on May 15, 2005, at 9:06:09
> > hi larry, i posted a windy reply to this hours ago, yet i must have ditched it...
>
> Doncha HATE that? The second time around is never as good.*** i'm with you on that one: something about a wind that blows twice as hard blows half as long???? ***
>
> > if you go to the 2003 archives of CDER, you will find the NDA # for Eldepryl, and in the 1997 archive, mention of - but no links that work (for me) - three (3) supplemental notations, likely the labeling and other changes. it appears that emsam is a ghost or a well-kept secret.
>
> Right. Exactly. It's approved as anti-Parkinsonian.
>
*** the recurring theme...yet absent of supporting documentation....****> > i am not aware of any reason why sundry letters would be held by the FDA/other...the closest thought i ahve - not borned by limited experience - is that if a drug is about to fill the shelves, then a media blackout from the gov't is warranted as it might fuel trading in financial markets. just a guess, and the NDA # for Eldepryl is 020647, approved 05/15/1996, labeling revision 08/06/1997, and control supplement 02/15/2001.
>
> But, Somerset had another NDA, for the same drug, under 019334, which was simply withdrawn. Approved in 1989, so it's not expired yet.**** yes, yes, yes, and the date i have for #019334 is in reference to the changes in labeling, and was approved 06 AUG 1997 in concert with the labeling supplements for #020647:
http://www.fda.gov/cder/da/da0897.htm
i asserted that an NDA (or was it IND? no matter, in truth) for a new delivery route is not going to cut it: this statement is incomplete and untrue, and it is not clear to me why any company would invest time/money/etc. to go down that road, and the conditions that preclude such a path for granting an approval/responding with approvable status are rarely if ever met (including no intention to actually follow through with supplying results from trials that support efficacy for the same malady BUT with fewer adverse effects: why bother? answer: they do not)
>
> > the NDA went to somerset, and therapeutic equivs for aaipharma, clonmel, and torpharm are given, although the reference - somerset's 5 mg selegiline HCl oral tablet - is TE == AB (unusual), and the generics are AB (par for the course...)....a mystery indeed...yours, c
>
> So, I'm baffled. How does one get a therapeutic equivalent on a newly approved med? Only if there is no patent, right?**** preamble: the TE is assigned based on bioequivalence in vivo/vitro in reference to, well, the reference drug. if emsam exists and is marketed sometime: it will carry a TE of AA for one dosing strength, and to this all others will be measured. why eldepryl and the generics are all AB is beyond me, as this indicates that none of those medications are the reference, nor is the reference given. ??????? je ne sais pas....****
**** the breeze is back: again, there are ways to extend the patent life. the problem is that the 17 year term which would cover the 1989 listing (please direct me/others if you please, i cannot locate the NDA/IND/other for that date but would like to see the timing) expires in one year from now, but because the patent is granted for a drug long before it hits the market - if at all - the company holding it gets a reduced term. the legislative branch of the u.s. government made law that a 5-year extension - and this is a full extension, not an exclusivity such as with generics - is the maximum that can be added to make up for lost time. regardless, from FDA approval to patent relief (immediately followed by 6 months of exclusive generic marketing to one and only one lucky generic manufacturer before the market opens entirely), 14 years is the max - this is explained ad nauseum on the fda/cder sites...
now, the tricky part: if, upon tacking on 5 years to a drug that is approved, the 14 year term is exceeded, the 5 years is revoked. if a drug is approved one day after the nine-year mark from patent grant, the 14 years + 1 day immediately goes to 9 years and 1 day of patent exclusivity.
this leads to the 1989 withdrawl you cite (i am with you 100%, just lost in re: finding it): the drug was patented in the u.s. for the first time in 1986 to the Hungarian company Chinoin, thus the clock ran out in 2003 UNLESS supplemental labeling changes were made - and they were - and the drug was pushed along, before mylan and watson coalesced and went for the approval to which you refer. this is within the time that patents were granted for 17 years - 20 is the figure now, and for the last 10 years or so - and 3 years were lost (1986-1989, and no, the u.s. does not play the time-game based upon the much earlier french and danish patents for same drug, same company), and the 5-year extension had not yet come to light. so, looking at 11 years of marketing freedom, and maybe (???) this was incentive to pull the application: maybe the data were weak, maybe the truth - that eldepryl is to be used in concert with sinemet/sinemet CR (from somerset's own web site, where the ``physician's info'' in under construction and the site was last updated in 1998), a medication that was under patent to merck and marketed by dupont (according to the somerset site) - is that there just is not a large market for a drug that is to be added to a cocktail for a person suffering from parkinson's while incidentally lowereing the need for a drug not marketed by somerset. i certainly do not know, and the crop-circle/area 51 people are not in short supply if you take a brief tour of the web space out there, as the government conspiracy and cover-up theories concerning alleged deaths from the drug (???) are not in short supply.
>
> And, it's quite clear that the FDA is hanging tough on the two reported cases of tyramine reaction, on 5 mg b.i.d. *oral* selegiline.**** why not? the low dose causality alone gives me pause. truth time: we are a society - the u.s., in my opinion - best characterized as looking for a lawsuit, whether merited or not. the FDA states that the risk is non-zero: fact. the consumer and prescriber ought to make it a point to address this, as it is a rare but severe reaction that might occur: who was the genius ingesting ephedrine and selegiline, for instance? and why should any entity be held responsible for such behaviour, including taxpayers who do not factor such acts into their budgets and lives? ***
>
> No selegiline trial comes up at http://www.clinicaltrials.gov/
> Already done?**** who knows...for a drug patented in france in 1964, the 40+ year limbo seems rather bizarre to me...****
>
> I checked the orange book listing for selegiline. There are 13 approvals, and the Somerset and Apotex products have been used by others as the comparator for substantial equivalency. There are no existing patents or exclusivity limits for selegiline.
>
> Anyway. Hmmmphhh.
>
> Lar
Posted by yldouglas on June 14, 2005, at 18:40:32
In reply to Re: ....patent expired » Larry Hoover, posted by chemist on May 15, 2005, at 23:39:59
I would hope no one would be so quick to judge a person regarding a post to a board such as this, when a) I was only trying to help and only reported information as I understood it at that time b) my life shortly after posting blew up in my face including having to vacate my living quarters of 25 years, stay in one hotel after another, until I found the studio I am now in without one piece of furniture (I am awaiting the delivery of a custom futon, meanwhile I sleep on the floor of an empty apartment), had a two-week long migraine, was improperly locked up in a psyche ward for 4 days with the help of my 3 closest friends who killed me with kindness, have since been diagnosed with two more medical problems both having to do with male-only issues, so for the chemist to take such a snide swipe at my posting says more about him than me, your arrogance is a wonderful thing to withhold. But if it got you to post the information you do have, I'm glad I took the time to post which I don't know if I have ever done so in the past, and will certainly be reluctant to do so in the future. (maybe next time you could be more proactive than reactive, oh I forgot, you're a chemist)
Effectiveness is the measure of truth--Ancient Hawaiian principle (from what is now called Huna) Go ahead and beat me up on that as well. I look forward to it.
Aloha kakou,
yldouglas
ps--please do not expect any replies to future postings, just to be clear.
Posted by Dr. Bob on June 14, 2005, at 22:02:06
In reply to Re: ....patent expired, posted by yldouglas on June 14, 2005, at 18:40:32
> your arrogance
I'm sorry you've been having a hard time, but please don't post anything that could lead others to feel accused or put down.
If you or others have questions about this or about posting policies in general, or are interested in alternative ways of expressing yourself, please see the FAQ:
http://www.dr-bob.org/babble/faq.html#civil
Follow-ups regarding these issues should be redirected to Psycho-Babble Administration. They, as well as replies to the above post, should of course themselves be civil.
Thanks,
Bob
Posted by yldouglas on June 18, 2005, at 10:43:33
In reply to Re: please be civil » yldouglas, posted by Dr. Bob on June 14, 2005, at 22:02:06
Did you read any of the messages posted after mine, specifically from the chemist. He basically calls me a liar, makes fun of me, and gets testy that I haven't responded. I was glad to get the information he had, but instead of belittling my post he could have simply stated his information, which I indeed found useful and enlightening. But he was being arrogant and it was directed at me. I hardly find that being civil.
Everything I put in my original post was true as far as what happened. Twice when I contacted the people in charge of cust. serv. for investors, I received calls in which they told me exactly what I reported. If I was a dupe in believing what they told me, so be it.
True, I sunk to his level, perhaps even lower. But it seems there's a bit of a double standard here. I am copying in the exact verbage "the chemist" used that I found most offensive, and perhaps then you'll understand why I wrote what I wrote, and believe me I will never post on this board again, or any other. I truly was just trying to be helpful to those wondering what was going on with the Emsam patch. I don't mind being corrected or someone else offering what they know (And I repeat, I was glad to get the information the person had, but why did they have to make it personal, not to mention, why wasn't this person making this information available without it being a reaction to someone else's post?? Namely mine!)
Here are the references from "the chemist"'s postings:
"the claim that only persons involved in the financial sections of the pharmaceutical companies have provided information concerning emsam - especially information way out of their collective area of expertise and to a stranger, no less, who contacted these parties and found that they were willing to hand out company secrets - is beyond absurd. thus, i eagerly await contact from this poster so i can better position myself with my broker for the day that the letter of approval comes through - if it comes through."
"...this is all academic, however, as it is not just slightly entertaining that a new PB post is presenting nothing more than an advertisement for emsam: it is misleading and worse, some readers will actually believe what is stated." (I'm not sure how much harm this would have done)
"the original post leans more than a little in the direction of ``a wonderful drug is being held from the needy and because i can only glean information from the financial departments of the pharmaceutical companies involved - and not the scientific arms - there is obviously something amiss.''
"nor is there any evidence to support or prove false any claim a distribution partership with BMS is anything other that a business arrangement. the original poster claims that BMS is involved for reasons that include the perceived might that it has in pushing drugs to market which are otherwise held in limbo at the FDA"
(Here I could have defended myself, as my sister was an executive in marketing at BMS until she retired earlier this year, and she was well-known for knowing how to work with the FDA to speed up drugs to the market, working hand-in-hand with the R&D scientists, but I'm not going to drag my sibling into another kind of rivalry that happens mainly between men -- a "pi__ing contest.")There's more but I would hope this would be enough and if you don't find anything snide and therefore, uncivil, then I really am lost. I simply cannot emphasize enough that my original post was true as I knew at that time and I indeed was contacted by two people from Mylan and Watson who claimed to be part of the investment group, and were responding to my email. And perhaps I was a chump for believing them, but I didn't make it up.
I hope this helps you understand why I was less than civil, but I didn't start it and you obviously did not call "the chemist" on his lack of civility. But my ego got involved and when that happens my wit does bave a bite which made it more obvious than that of "the chemist."
And I would hope you would respond to this. I'm assuming you will catch this as well so it will not actually be posted, especially after I stated I would not be posting again. And please, do not refer me again to your FAQ's on being civil, it needed no explanation.
Aloha kakou,
yldouglas.
Posted by Dr. Bob on June 18, 2005, at 11:34:25
In reply to Re: please be civil » Dr. Bob, posted by yldouglas on June 18, 2005, at 10:43:33
> a new PB post is presenting nothing more than an advertisement for emsam: it is misleading and worse, some readers will actually believe what is stated.
>
> the claim ... is beyond absurd.
>
> chemist> he was being arrogant
>
> yldouglasPlease don't post anything that could lead others to feel accused or put down.
> I am copying in the exact verbage "the chemist" used ... and perhaps then you'll understand why I wrote what I wrote
Thanks, I'm sorry I missed that. Still, two wrongs don't make a right...
If you or others have questions about this or about posting policies in general, or are interested in alternative ways of expressing yourself, please see the FAQ:
http://www.dr-bob.org/babble/faq.html#civil
Follow-ups regarding these issues, as well as replies to the above posts, should of course themselves be civil.
Thanks,
Bob
Posted by Ron Hill on June 18, 2005, at 14:49:04
In reply to Re: History of emsam as I know it » yldouglas, posted by chemist on May 11, 2005, at 21:31:06
> the MAO-A/B switch that you mention is a mystery: the drug is an MAO-B inhibitor as low doses, and a dopamine uptake inhibitor at high doses.
Do you have any pharmacological research data that support the claim that Selegiline is a dopamine uptake inhibitor at high dosages and that it is not an MAOI-A? The medical research data repeated state that Selegiline is a selective MAOI-B up to a dosage of about 15 - 20 mg/day at which point it loses its selectivity and becomes an MAOI-A and an MAOI-B.
Therefore, please post the link(s) that support the claim that Selegiline is a dopamine uptake inhibitor at high dosages and not an MAOI-A.
-- Ron
BP II and OCPD
600 mg/day Lithobid
900 mg/day Trileptal
50 mg/day Lamictal (level limited by rash)
5 mg/day Deprenyl (as tx for atypical depression)
Posted by Dave001 on June 20, 2005, at 19:19:12
In reply to Re: Selegiline Pharmacology » St James » Oracle » chemist, posted by Ron Hill on June 18, 2005, at 14:49:04
>> the MAO-A/B switch that you mention is a mystery: the drug is an
>> MAO-B inhibitor as low doses, and a dopamine uptake inhibitor at
>> high doses.
>
> Do you have any pharmacological research data that support the claim
> that Selegiline is a dopamine uptake inhibitor at high dosages and
> that it is not an MAOI-A? The medical research data repeated state
> that Selegiline is a selective MAOI-B up to a dosage of about 15 - 20
> mg/day at which point it loses its selectivity and becomes an MAOI-A
> and an MAOI-B.
>
> Therefore, please post the link(s) that support the claim that
> Selegiline is a dopamine uptake inhibitor at high dosages and not an
> MAOI-A.I'm not the person to whom your post is in response, but I thought I
would add that for the most part, your understanding is in line with the
current medical understanding of selegiline.It does appear to retain its selectivity for MAO-B at the doses
typically used to treat Parkinson's disease. (Or at least, the level of
MAO-A inhibition does not seem to be clinically significant at those doses.)I am also not aware that at higher doses a prominent inhibitory effect
of dopamine uptake is present. Then again, that is not an issue that
I've spent a lot of time trying resolve... Perhaps it is true. One paper
I've seen did indicate an inhibitory effect on dopamine uptake from
deprenyl (Fang and Yu, 1994). However, the effect from l-deprenyl was
quite weak on that parameter; by contrast, *d-deprenyl* was quite potent
at inhibiting dopamine uptake. Perhaps "chemist" or whomever it was that
contradicted your understanding, mistakenly confused the optical isomers
of deprenyl. Selegiline is l-deprenyl. That's just speculation though;
you'll have to wait for him to clarify the discrepancy.Dave
Reference:
Fang, J. and P. H. Yu (1994). "Effect of L-deprenyl, its structural
analogues and some monoamine oxidase inhibitors on dopamine uptake."
Neuropharmacology 33(6): 763-8.
Posted by Ron Hill on June 21, 2005, at 10:46:52
In reply to Re: Selegiline Pharmacology, posted by Dave001 on June 20, 2005, at 19:19:12
> ...the effect from l-deprenyl was
quite weak on that parameter; by contrast, *d-deprenyl* was quite potent
at inhibiting dopamine uptake.
-------------
Dave,Thank you for the information. Interesting how much difference a mirror image can make. Thanks again. Good info.
-- Ron
BP II and OCPD
600 mg/day Lithobid
900 mg/day Trileptal
50 mg/day Lamictal
5 mg/day l-Deprenyl (as tx for atypical depression)
Posted by Ron Hill on June 21, 2005, at 11:21:34
In reply to Re: please be civil » Dr. Bob, posted by yldouglas on June 18, 2005, at 10:43:33
> Did you read any of the messages posted after mine, specifically from the chemist. He basically calls me a liar, makes fun of me, and gets testy that I haven't responded.
-----------------yldouglas,
I'm very sorry that you got beat up early on in this thread. When I first read the thread a month or so ago I became very angry. In fact, I was too angry to post at the time. But I think I can trust myself to post now that some time has passed.
I'm also sorry that your living arrangements were disrupted and that you had an unexpected visit to the hospital. How are you doing now? If you don't mind my asking, what is your dx and what are your current meds? Do you feel like your meds are working satisfactorily?
Please know that there are people here that care and I hope you feel welcome and accepted. Let me know if I can help.
-- Ron
BP II and OCPD
600 mg/day Lithobid
900 mg/day Trileptal
50 mg/day Lamictal
5 mg/day Deprenyl (as tx for atypical depression)
Posted by Dr. Bob on June 22, 2005, at 20:24:44
In reply to Re: Med Check. Doing Okay? » yldouglas, posted by Ron Hill on June 21, 2005, at 11:21:34
> I'm very sorry that you got beat up early on in this thread.
It's great to support yldouglas, but please don't post anything that could lead others to feel accused.
If you or others have questions about this or about posting policies in general, or are interested in alternative ways of expressing yourself, please see the FAQ:
http://www.dr-bob.org/babble/faq.html#civil
Follow-ups regarding these issues should be redirected to Psycho-Babble Administration. They, as well as replies to the above post, should of course themselves be civil.
Thanks,
Bob
Posted by yldouglas on June 24, 2005, at 17:30:48
In reply to Re: Med Check. Doing Okay? » yldouglas, posted by Ron Hill on June 21, 2005, at 11:21:34
> > Did you read any of the messages posted after mine, specifically from the chemist. He basically calls me a liar, makes fun of me, and gets testy that I haven't responded.
> -----------------
>
> yldouglas,
>
> I'm very sorry that you got beat up early on in this thread. When I first read the thread a month or so ago I became very angry. In fact, I was too angry to post at the time. But I think I can trust myself to post now that some time has passed.
>
> I'm also sorry that your living arrangements were disrupted and that you had an unexpected visit to the hospital. How are you doing now? If you don't mind my asking, what is your dx and what are your current meds? Do you feel like your meds are working satisfactorily?
>
> Please know that there are people here that care and I hope you feel welcome and accepted. Let me know if I can help.
>
> -- Ron
>
> BP II and OCPD
>
> 600 mg/day Lithobid
>
> 900 mg/day Trileptal
>
> 50 mg/day Lamictal
>
> 5 mg/day Deprenyl (as tx for atypical depression)
>I want you to know I really appreciate your kind words and concern. I tried to answer your posting two days ago and lost it, probably due to the fact I use wifi. I want people to know I don't think I am any expert, I was just reporting what I had been told and thought I knew at the time. I never have a problem saying "I stand corrected." Even if it turns out later I was not incorrect. Macht nichts.
The irony of the entire incident is that the way I got back to this board. I was just checking if there was anything new out there in cyberspace on emsam, so I went to google and typed in emsam patch and the number one listing turned out to be my posting and the thread that followed. Oh the triksters of the universe just love to play with me. I find it very humorous now. But I want to get away from the board. I'm happy to talk offline either by phone or email. But I don't know if there is a policy against listing private email addresses or pnone numbers. So I need someone to advise me on how to proceed. God forbid I should break any more rules.
Thanks again -- Mahalo nui loa
douglas.
Posted by ed_uk on June 24, 2005, at 18:01:52
In reply to Re: Med Check. Doing Okay? » Ron Hill, posted by yldouglas on June 24, 2005, at 17:30:48
Hi,
>But I don't know if there is a policy against listing private email addresses or pnone numbers.
People often post their email address :-)
~Ed
Posted by Ron Hill on June 24, 2005, at 19:51:31
In reply to Re: Med Check. Doing Okay? » Ron Hill, posted by yldouglas on June 24, 2005, at 17:30:48
Douglas,
> But I want to get away from the board.
I'm sorry that you no longer are comfortable at PB. But I think I know what you are feeling.
> I'm happy to talk offline either by phone or email. But I don't know if there is a policy against listing private email addresses or pnone numbers. So I need someone to advise me on how to proceed. God forbid I should break any more rules.
As far as I know, it's not against the PB rules to list private e-mail addresses. However, I wouldn't do it if I were you. The spammers might pick it up. And I definitely would not list a phone number.
Instead, Dr. Bob has given us a safer way. It's called Babblemail. Are you familiar with it? Babblemail messages do not display on any of the boards. I sent you a Babblemail a week or so ago, but I didn’t hear back. Therefore, I assume you do not have the feature turned-on on your end.
Here is a block-copy-and-paste of the Babblemail instructions contained in the FAQ section of the PB site:
<start FAQ excerpt>
This site lets members send messages ("babblemail") directly to each other using just posting names. The messages are sent as email, but by the server, so the sender doesn't need to know the recipient's (and the recipient doesn't find out the sender's) email address. To give it a try, go to the babblemail form. If you want, test it out by sending a message to yourself. Babblemail is turned off by default. To turn it on, update your registration and check the "accept babblemail" box.
If someone abuses this feature, they'll be blocked from using it (and from posting). Likewise, if someone's blocked from posting, they'll be blocked from using babblemail. My plan isn't to monitor babblemail directly, but to ask recipients to contact me if they feel it's been abused. I guess if it comes to that, the usual civility guidelines will apply. To be able to verify that specific babblemails were sent, my idea is to keep a log of who babblemails whom, when, and "fingerprints", but not actual copies, of messages.
<end FAQ excerpt>
Douglas, if you want, please send me a babblemail message and you can tell me your personal e-mail address in a safer environment. I will then reply by sending a message to your personal e-mail address. As it stands right now, I can’t send a Babblemail to you because I don’t think it’s turned-on on your end.
Be well.
-- Ron
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.