The information below is a cut and paste from the founders statement at SSRI Citizen.  The site has long been shut down.  It is my guess, another financial settlement was paid, which with GSK, comes with a gag order.  You decide....  

Shortly, at the bottom of this page, I will post a full seven page gag order that GlaxoSmithKline has one sign when a financial agreement is reached.

The History of Paxil (and a whole lot more)

"Penetrating so many secrets we cease to believe in the unknowable. But there it sits nevertheless, calmly licking its chops." — H.L. Mencken

"Ferrosan"
In the 1960's a small Danish company called Ferrosan entered into (according to their web site) "a successful venture into CNS (Central Nervous System) research, which led to the discovery and launch of the antidepressant Seroxat / Paxil, now owned by GlaxoSmithKline".

Ferrosan is almost always referred to as a Danish company — but in a document issued by the United States Federal Court of Appeals concerning a highly technical and convoluted patent dispute relative to paroxetine (See: SmithKline Beecham Corporation and Beecham Group, P.L.C. v. Apotex Corp., Apotex, Inc., and Torpharm, Inc. ) — Ferrosan is referred to as "a British company." In any event, Ferrosan was a family owned enterprise; the Danish part of the group remained so until 1986 when it was acquired by Novo Industri A/S (now Novo Nordisk A/S). After the acquisition, the CNS (Central Nervous System) research activities, the distribution of prescription medicine, and the veterinary medicine activities were all merged into the corresponding divisions of Novo Industri A/S.]

By the way, the suit just mentioned was resolved on April 23rd, 2004 in favor of Apotex Corp., Apotex, Inc., and Torpharm, Inc.

Leading the research team of Ferrosan was an individual, Dr. Jorgen Buus-Lassen, who supported the theory that the specific enhancement of serotonin might lift a depressive mood. But Dr. Buus-Lassen was not a doctor in the ordinary sense of the word, but rather a "DVM" or "Doctor of Veterinary Medicine". In other words: Buus-Lassen is licensed to be an animal doctor. Buus-Lassen received his DVM credentials from the Royal School of Veterinary and Agriculture Science in Copenhagen.

With his associates Buus-Lassen explored approximately 100 compounds before deciding on the one that the world would come to know as "paroxetine" and, ultimately, Paxil in the United States. Buus-Lassen's first paper on paroxetine was published in 1975.

In 1989 Buus-Lassen wrote a piece entitled "Introduction to the development of paroxetine, a novel antidepressant." [Acta psychiatr. scand. (1989) 80: 13.] I found Buus-Lassen's choice of the word "novel" mephistophelean; he uses it to indicate a compound "of a kind not seen before". He sure got that right — because Paxil is the spawn of Hell. God willing, the world will never see another "novel" antidepressant like it.

I arranged to obtain a copy of the Buus-Lassen "intro" with hopes it would provide a "ham hock of history" I could toss into the investigatory stew I was in the process of cooking up. When it arrived, the document turned out to be a terse four paragraphs. Of those, two were single sentences. At the bottom of the page were nine footnotes.


Jorgen Buus-Lassen, DVM
Primogenitor of Paxil

Later, Buus-Lassen would recall during an interview with the "Guardian Unlimited", a British newspaper, that "It (paroxetine) didn't work with all patients. In most studies we could just show that we had about the same efficacy as the older tricyclic antidepressants. We didn't see a better effect."

A better effect? Like ... drug withdrawals sent from Hell? If you'd like to email Buus-Lassen a note you can do so care of: ns@neurosearch.dk. I expect tens (perhaps hundreds) of thousands of you have a word (or two) you'd like to share with Mr. Buus-Lassen. (Be sure to mention the SSRI Citizen web site.) My bet is after he's received a few thousand emails a firewall will be installed to screen out incoming "slings and arrows". If so, don't be disappointed ... we'll find another address for him faster than you can pitch a new prescription for Paxil in the closest garbage can. Failing that, there's always "snail mail", and of course the phone.

Ferrosan patented the formula for the "Buus-Lassen compound" in 1977 under U.S. Patent #4,007,196. The patent claims paroxetine and its salts and discloses their antidepressant properties. Ferrosan eventually developed a process to produce the crystalline hydrochloride salt of paroxetine, or paroxetine hydrochloride (PHC).

In 1980, Ferrosan licensed the #4,007,196 patent and its other "PHC-related technology" to SmithKline. SmithKline began manufacturing PHC in its Harlow plant in England.

In March 1985, a chemist in SmithKline’s Worthing, England laboratory, Alan Curzons, created a new crystalline form of PHC while attempting to improve PHC production. Curzons’ test results established that the new product was the hemihydrous form of PHC (PHC hemihydrate), while Ferrosan’s original form was anhydrous PHC (PHC anhydrate). PHC anhydrate comprises crystals of PHC without bound water molecules. PHC hemihydrate comprises PHC crystals with one bound water molecule for every two PHC molecules. PHC hemihydrate proved more stable and thus more easily packaged and preserved.

Further review of the SmithKline samples showed that the Harlow plant had unwittingly made PHC hemihydrate as early as December of 1984.

In May 1985, SmithKline began double-blind clinical tests in the United States to determine the "safety and efficacy" of PHC hemihydrate capsules to treat depression symptoms.

On October 25, 1985 SmithKline filed a patent application in the British Patent Office relating to “crystalline paroxetine hydrochloride, its preparation and its uses as a therapeutic agent.” The British application identified the invention as both the hemihydrate and the anhydrate form of PHC, as well as mixtures that contain a major portion of either form.

On October 23, 1986, SmithKline filed a U.S. application claiming priority to a British application that issued as the #4,721,723 patent in 1988. The ’723 patent does not claim PHC anhydrate and does not claim mixtures of the two PHC forms.

If you would like to take an in-depth look at all of the U.S. patent records as they pertain to Paxil click here.

And while you're there: Who can explain the patent for "Methods and compositions for reducing toxicity of a toxic agent are provided in which a polysaccharide, galactomannan is co-administered with a therapeutic agent in a liquid formulation to a subject to reduce toxicity of the agent for the subject." Click here for link

Scroll down through this record to where it reads: "Examples of therapeutic agents with toxic side effects that may be administered with galactomannan to reduce their toxicity include the following: Anti-infectives including antibiotics, antivirals and vaccines, antineoplastics, cardiovascular drugs including antiarrythmics, antihypertensives etc., central nervous system drugs including analgesics, anorectics, anticonvulsants, anti-inflammatories and tranquilizers etc. OTICS, Opthalmics, gastrointestinal including anti-ulcer drugs, anticholinergic drugs etc. hormones, respiratory drugs including allergy medications, bronchodilators and decongestants, topical drugs and vitamins and minerals. Particular examples in the above categories are provided by way of illustration. Prilosec (AstraZeneca) described in U.S. Pat. No. 4,255,431 and Prevacid (TAP) described in U.S. Pat. No. 4,628,098; Lipitor (Pfizer) an anti-cholesterol drug described in U.S. Pat. No. 5,273,995. The antihyper-lipidemic agent, Zocor (Merck) U.S. Pat. No. 4,444,784; anti-depressants such as Prozac (Eli Lilly) described in U.S. Pat. No. 4,314,081; and Zoloft (Pfizer) described in U.S. Pat. No. 4,536,518; Paxil (SmithKline Beecham) U.S. Pat. Nos. 3,923,743 and 4,007,196; 4,721,723; antipsychotic agents such as Zyprexa (Eli Lilly) hematinic agents such as Epogen (Amgen), also known as Erythropoietin, and anti-inflammatory agents such as Celebrex (Searle).

It seems a bit odd that three of the four antidepressants which are the focus of the SSRI Citizen web site — Prozac, Zoloft and Paxil — are included as specific "examples of therapeutic agents with toxic side effects that may be administered with galactomannan to reduce their toxicity". What happened to FDA approved "safe and effective"? My doctor didn't mention anything about "toxic side effects" when she dashed off my prescription for Paxil. Did yours?

"Have nothing to do with the evil deeds of darkness, but rather expose them." — Ephesians 5:11

"SmithKline Beecham and the Gates Of Hell"
Beecham — patent #4,007,196 licensing in hand from Ferrosan — after merging with another drug company called SmithKline & French (to become SmithKline Beecham a.k.a. SKB), would eventually become the company responsible for flinging wide the laboratory "gates of hell", thereby allowing the "demon of Paxil" to find its new home in the medicine cabinets of America (and the world.)

Of course, before Paxil could be sold in the United States SKB had to gain approval from the Food And Drug Administration certifying Paxil as " safe and effective". So in the 1980's SKB undertook a series of Paxil human clinical trials. Most interesting (to me as a Paxil survivor) were those conducted in Yugoslavia in the late 1980's. To SKB's dismay the Yugoslavia trials were an unmitigated disaster; the company was having a hell of a time coming up with tests they could present to the FDA proving the drug was safe and effective. Billions of dollars in anticipated profits were imperiled. So what did SKB do? Using a bit of " the devil's math" they "fixed" the studies so Paxil would "wow" the FDA. Which led to the following lawsuit against SKB (now GSK): paxilcomplaint.html

Exiting Yugoslavia (phony studies in hand) SKB submitted Paxil's application to the FDA and — through a combination of agency ineptitude, stupidity and insider collusion — Paxil was approved by the FDA for sale in the U.S. on October 5th, 1992.

In 1993, SmithKline placed "its" antidepressant drug (with PHC hemihydrate as the active ingredient) on the market under the name Paxil. (For the record: Paxil was actually first sold in the UK, in 1991, under the trade-name "Seroxat", but I'll leave that history for someone else to pick apart.)

What has followed is a mind-boggling swath of human misery (and sometimes death) for God-only-knows how many people. And its far from over; for that you can thank people like football-legend-turned-Paxil-pitchman Terry Bradshaw who is now being paid millions of dollars to serve as GSK's "Pied Piper of Paxil"; in effect, luring thousands of unsuspecting new victims over the edge and into depths of the Paxilian abyss. Much more on him later (elsewhere at this web site.)

But the real story of Paxil is only beginning. For reasons still not fully apparent a trademark for Paxil was applied for on March 28th, 1980 with the United States Patent and Trademark Office (under "Goods & Services") as a "hypnotic drug for human use". But not by Ferrosan or Beecham, but instead by the German drug company of Boehringer Ingelheim G.m.b.H. To view this U.S. government database record go to the following web page and click on "Search Trademarks". A new window will appear. Under the "Select The Search Form" click on "New User Form Search (Basic)". As the next page appears type the word "Paxil" in the "Search Term" field. Next, click on the "Submit Query" button. Another page with records set up in a grid format will appear. Scroll down to the record which displays serial number "73255881". Right of that is a registration number: "1170889". Click on the word "Paxil" just right of the registration number, and the full record will be retrieved. Note: The official registration date for the Boehringer Ingelheim trademark is listed as September 29, 1981 and a "termination" date of April 7, 1988.

The existence of this seemingly (at first glance) ordinary record educed an extraordinary question: Did Boehringer Ingelheim enter into a joint venture with Ferrosan in the 1960's — whereby Jorgen Buus-Lassen was provided the (approximately) 100 compounds he studied — of which one went on to become Paxil?" Ferrosan was a relatively small company, and it is my surmise they did not create the 100 or so compounds Buus-Lassen studied, but rather acquired them "off the shelf" from a much larger company with the resources to make them ... like Boehringer Ingelheim. What followed would have been an agreement whereby Boehringer Ingelheim told Ferrosan if it came up with anything marketable from the compounds they would serve as distributor.

If this is not the case, why did Boehringer Ingelheim and not Ferrosan, or Beecham (later becoming SKB), register Paxil on March 28th, 1980, with the United States Patent and Trademark Office? The only logical (and inescapable) explanation is Ferrosan and Boehringer Ingelheim had a substantial business agreement regarding Paxil. One that apparently went "poof" the very same year Ferrosan licensed SmithKline the #4,007,196 patent and its other "PHC-related technology". This connection spurred me to take a closer look at Boehringer Ingelheim.

But before doing that, there's a bit more yet to that Boehringer Ingelheim trademark registration. Why, I wondered, did Boehringer Ingelheim classify Paxil as a "hypnotic" — and not an antidepressant? That was not a random designation. Far from it: One of the two companies, either Ferrosan or Boehringer Ingelheim, had conducted research and studies that suggested this was the best way to, pharmacologically speaking, describe the drug's effect. Where is that data now? In SKB's (now GSK) confidential company files?

This led to another question: Why did SKB begin selling Paxil in the United States as an antidepressant and not a hypnotic? And still another: How was "Paxil the hypnotic" transformed by SKB into "Paxil the antidepressant"? After all, hypnotics are central nervous system (CNS) depressants. (Webster's dictionary defines a hypnotic as "Any agent that produces, or tends to produce, sleep: an opiate; a soporific; a narcotic." One medical dictionary simply defines a hypnotic as a "sleeping-tablet".) Why, you might ask, does it matter?

Perhaps it doesn't. However, it might have been (rigged studies notwithstanding) more difficult to gain FDA approval if SKB had tried to "pitch" Paxil to the agency as a hypnotic. Worse yet, it might have led to Paxil's scheduling by the FDA as a "controlled substance". (Which it should be.) Or maybe it would have been harder to position Paxil in the marketplace to compete with Lilly's multi-billion dollar Prozac profit engine ... which was being sold as an antidepressant. Or maybe all of the above.

Whatever the case, one has to wonder if Paxil is soon destined to end up in the pharmaceutical trash-bin of history ... just like Halcion (another hypnotic) did. If the name of that drug (which was banned in Britain) doesn't jog your memory ... here's a Newsweek magazine article that will.

Other questions that must be asked and which will — one day soon — be answered by SKB (now GSK) include:

*What did the companies involved in the creation and eventual distribution of Paxil know about the drug's propensity to induce addiction and dependency? When did they know?

*About the horrifying and protracted drug withdrawals Paxil can induce? When did they know?

*About Paxil's potential to trigger homicidal or suicidal behavior? When did they know?

*Is it possible the answers going to be found in Boehringer Ingelheim files passed onto Ferrosan?

*Or was it Ferrosan who first discovered the horrifying truth about Paxil? (After Buus-Lassen's mice dosed with paroxetine started chewing their own legs and tails off, or attacking other mice.)

*Or was it SmithKline Beecham?

The world will soon have the answer to these questions (and a whole lot more) when the first Paxil withdrawal lawsuit goes to trial. For now, only the drug companies and the plaintiffs' attorneys know the ultimate answers.

"For our struggle is not against flesh and blood, but against the rulers, against the powers, against the world forces of this darkness, against the spiritual forces of wickedness in the heavenly places." — Ephesians 6:12

"Boehringer Ingelheim: Black Widow At
The Center Of The 'SSRI Web'?"
The net effect of the questions I've posed thus far prompted me to begin looking a bit closer at Boehringer Ingelheim. Here's what I discovered: Boehringer Ingelheim is one of the twenty largest drug companies in the world; it has strategic partnerships with many other multi-national pharmaceutical corporations, including SSRI giants GSK and Lilly — as well as a new company called NeuroSearch which is headed up by none other than the "father of Paxil" himself — Jorgen Buus-Lassen. Much more on this in a few minutes (read on). Boehringer Ingelheim's web site

Probing the history of Boehringer Ingelheim, I discovered the company garnered some bad press after it was widely reported it had, under the direction of Richard von Weizsacker, supplied the United States government with large quantities of a highly toxic and dangerous herbicide called dioxin (a.k.a. "Agent Orange") during the Vietnam War. Weizsacker eventually left the company and went on to become president of the Federal Republic of Germany in 1984.

In a 1991 article that appeared in "The Mirror" in Germany, dioxin was described as "the most poisonous chemical in the world". Elsewhere, I have come across estimates that suggest as many as one million Vietnamese died as a result of exposure to dioxin delivered by U.S. war planes. Dioxin is, in short, a weapon of mass destruction.

By the way ... Weizacker's father, Baron Ernst von Weizsacker, served as state secretary in the foreign ministry of the German Republic from 1938-1943; in 1949 he was sentenced at the Nuremberg trials to seven years imprisonment for "crimes against humanity". Specifically, he was convicted for his use of diplomatic pressure to make possible the deportation of Slovakian and Italian Jews to Nazi death camps. His sentence was later commuted to "time served".

Baron Ernst von Weizsacker, defendant, during the Nueremburg trials. His son Richard von Weizsacker, who worked at Boehringer Ingelheim in the 1960's, was later linked to the "Agent Orange" dioxin scandal.
In the 1990's, a study published in the journal of the United States National Cancer Institute provided conclusive evidence of a direct relationship between industry and the cancer-causing effects of dioxin. Generally ignored by the mainstream press, the study revealed that many thousands of workers in the U.S. chemical industry died of various cancer-related illnesses as a result of exposure to dioxin. Pooling data from more than 5,000 workers from 12 different factories across the United States, the study found that workers with the highest dioxin exposure had a 60 percent greater risk of dying from cancer than the U.S. national average.

Before reading on would you like to venture a guess as to where dioxin came from?

Dioxin was discovered in Hamburg, Germany in 1954 — at the company of C.H. Boehringer — by a scientist named Karl–Heinz Schulz who conducted a series of (depraved) experiments using "76 assorted Boehringer products".

The ultimate parent company of the Boehringer Ingelheim corporation is C.H. Boehringer Sohn. Boehringer Ingelheim GmbH, which is a subsidiary of C. H. Boehringer Sohn, is the central holding company for administrative purposes — the corporate central body which manages and directs the worldwide family of Boehringer Ingelheim companies and which delivers central services to all companies of the corporation.) For a bit more background information click here.

Schulz's sadistic dioxin experiments involved the use of live rabbits. Schulz would rub the ears of a control group of the animals with one of the 76 Boehringer chemicals. A second group of rabbits — housed alongside the control group and in open cages — was not treated with a test chemical. A few days after the first experiment commenced hideous boils appeared on the test rabbits' ears. Incredibly, the untreated rabbits in the cages next to the test rabbits were also affected — even though they did not come in direct contact with one of the chemicals; they began dying of liver necrosis (a condition whereby liver tissue practically rots). Schulz concluded the untreated rabbits were inhaling the chemicals applied to the control group rabbits. The one thing that all of the chemicals being tested had in common? They contained varying amounts of dioxin.

Subsequent to his rabbit experiments, Schulz reported to his employer that the compounds containing dioxin were, in his opinion, “too deadly” for any conceivable use. What did Boehringer management make of Schulz's report? They didn't like it, because the company had decided it wanted to unload many of the compounds into the American market — so they hid the test results. Boehringer subsequently sold most of these compounds to Dow Chemical in, according to one source, 1960. One of the compounds sold to Dow Chemical was the isolate dioxin. (Is any of this sounding familiar yet?)

Interestingly enough, a year prior to the sale of the dioxin et al. rights to DOW a representative of the United States Army Chemical Corps traveled to Boehringer to see what he could find out about dioxin's potential use — as a chemical weapon. Based on his report the U.S. military concluded that dioxin was too dangerous to be handled safely — although the U.S. military later discovered dioxin worked wonders when used as a defoliant (sprayed from airplanes) to clear vast tracts of lush vegetation in Vietnam (during the Vietnam war).

Digging further into Boehringer Ingelheim's past I tried to ascertain what, exactly, the company was doing in the 1930's and 1940's when Germany was controlled by the Nazi party. Specifically, what activities did Boehringer Ingelheim engage in during Hitler's reign that would prompt the company — after the collapse of the Third Reich — to join the German Forced/Slave Labor Compensation Fund? Does it have anything to do (as reported by the Shoah Project) with Boehringer "Compound 2516" studies ordered by Heinrich Himmler and carried out under the aegis of "Dr." Claus Shilling at the Dachau concentration camp? See for yourself. Go to the "Google" search engine at google and type in: "dachau" "boehringer" "2516". One of the first links that will appear should be one that reads "Shoah Project Dokumentation KZ Dachau"; immediately right of this phrase click on the text that reads "Translate this page". A new page will appear with German text translated into (approximate) English. Scroll down to the bottom of the page to the following passage which reads (verbatim):

Professor Dr. Claus Schilling
a set of experiments with the malaria preparation Boehringer 2516 let
accomplish. None of the 1200 chose ever in agreement explained
themselves or freieillig announced themselves. For these attempts
clergyman were often selected. The prisoners were infected by the
injection of the mosquitoes themselves or by injections of Extracten
from the Schleimdruesen of the mosquitoes with malaria.

Note: The Shoah Project's main web site can be found at:
www.shoahproject.org

Traveling back to the late 1800's I discovered that C.H. Boehringer & Sohn had "jumped into the cocaine trade" and was involved in the business for several decades ... possibly well into 1940's through World War II. See: "The Rise and Demise of Cocaine" by Paul Gootenberg at:

Today, Boehringer Ingelheim is participating in another "war". But this war is, ostensibly, for a noble cause. And potentially a very lucrative one. It is the "war on AIDS". Yet how Boehringer Ingelheim is participating in this war is raising some disturbing questions. For example: Boehringer Ingelheim is the manufacturer of an experimental AIDS drug called "Viramune" (nevirapine). The drug is being used in "clinical trials" involving infants and children at a place in New York's Washington Heights called the "Incarnation Children's Services" — as well as at Columbia Presbyterian and, in fact, at hundreds of participating hospitals in pediatric AIDS clinics nationwide. Coincidentally, GlaxoSmithKline (formerly SKB) is also participating in these "studies" with two of its drugs: Retrovir (AZT) and Epivir (3TC, lamivudine). Res ipsa loquitur: For further details visit "The House That AIDS Built."

"Cymbalta: Spawn of Boehringer Ingelheim and Eli Lilly"
In November, 2002, Boehringer Ingelheim and Eli Lilly (Prozac's manufacturer) signed a long-term agreement to work together and develop the commercialized use of a compound called duloxetine hydrochloride. Duloxetine, (trademark named "Cymbalta") is currently being developed for the treatment of a condition known as "stress urinary incontinence"... as well as depression. Lilly and its investors are counting on Cymbalta to be its next blockbuster antidepressant seller since Prozac has gone off patent and profits have gone "poof". Approval for Cymbalta by the FDA as "safe and effective" is right around the corner. But is it safe and effective? Read the following Philadelphia Inquirer article entitled "Suicide Of A Human Guinea Pig."

"A Family Reunion of Sorts: Boehringer Ingelheim
and Jorgen Buus-Lassen"
Boehringer Ingelheim is also hooked up with Jorgen Buus-Lassen (formerly of Ferrosan, creator of Paxil) who is now head of his own company called NeuroSearch (a Danish biopharmaceutical company listed on the Copenhagen Stock Exchange: NEUS:CO)

For its part Boehringer Ingelheim is investing a total of DKK 680 million in exchange for sales rights to a drug for Alzheimer’s and Parkinson’s disease that NeuroSearch is developing. DKK 170 million is being made available now, with the rest to follow over the coming years. Boehringer Ingelheim is taking on the future development costs of the drug. “It is the most important agreement in NeuroSearch’s history. The cash injection ensures that we can develop the drug for the ever more prevalent Alzheimer’s and Parkinson’s disease and bring it to market” says Buus-Lassen.

"All About NeuroSearch"
NeuroSearch was founded in April of 1989 by Buus-Lassen and five fellow researchers (Asger Aamund, Jørgen Drejer, Frank Wätjen, Leif Helth Jensen, Henrik K. Moltke and Peter Wulff) who left Ferrosan and struck out on their own, pledging their homes to get a startup loan. They first opened shop in a cellar at Danochemo (which specializes in laboratory medical equipment) based in Ballerup, Denmark. They obtained private financing in the amount of DKK 29.7 million for start up capital.

Today, the company is still located in Ballerup, Denmark (between the Copenhagen (DK) area and Skania in Sweden) in the so-called "Medicon Valley" (think Silicon Valley) which, as of October, 2002, was home to 26 hospitals and 12 universities with 4,000 researchers and 135,000 students. The area provides over 30,000 jobs in more than 160 biotechnology companies. See: www.mediconvalley.com

NeuroSearch's goal is to become an international leader in pharmaceutical research and development, with an intense focus on the central nervous system. The company intends to develop each of its compounds "in-house" to maximize the opportunity for potential profits. In other words: It won't buy bulk compounds "off the shelf" to experiment with — like Ferrosan did in the 1960's. (We won't make that mistake again. Right Mr. Buus-Lassen?)

Typically, NeuroSearch tries to broker agreements with large pharmaceutical companies to "optimize development and/or marketing". At the same time NeuroSearch seeks to preserve commercial rights for its compounds in the Nordic and Baltic countries "with the possibility of expanding these primary markets to larger parts of Europe".

NeuroSearch operates under an "in-house as long as possible followed by collaboration" model based on the following concepts:
1) "Collaborations established during the late clinical phases of a compound's development are generally more profitable than those started during the initial stages".

2) "A gradual increase in NeuroSearch's capabilities in the areas of drug development, manufacturing of compounds on a larger scale for extended clinical trials and, in the long term, sales of marketable products".

NeuroSearch currently has agreements not only with Boehringer Ingelheim and GSK (as noted above) but also Abbott Laboratories, along with partnerships enjoining Pharmexa and Pierre Fabre, and equity interests in eight biotech companies, including Bavarian Nordic A/S, NsGene A/S, and Sophion Bioscience A/S.

NeuroSearch maintains an Internet site at: www.neurosearch.com
Note: The site is not Macintosh accessible.

For a complete timeline highlighting NeuroSearch's history see: NeuroSearchHistory.html

"The SSRI Ties That Bind: NeuroSearch,
Jorgen Buus-Lassen and GlaxoSmithKline"
NeuroSearch's first accord involving GlaxoSmithKline (GSK) came (as noted in the history of the company, see link above) in 1993 with then Glaxo Group Research Ltd.

Ten years later and on December 13th, 2003, NeuroSearch and GlaxoSmithKline (which remember, now owns the patent for Paxil — first licensed to SKB from Ferrosan — the company Buus-Lassen used to work for) announced a landmark five-year research and development alliance. The alliance comprises a number of research programs, including the treatment of purported "diseases of the central nervous system" — like depression and anxiety.

NeuroSearch compound NS2710, intended to treat the "disease of anxiety", was originally slated for distribution by pharmaceutical giant Pharmacia & Upjohn; however, "problems" arose during the clinical "Phase II" human trials. Not that the compound wasn't "effective" according to NeuroSearch, but rather some patients experienced sedation or an allergic reaction. In other words NS2710 knocked them out or made them sick. The disclosure of these problems was serious enough that Pharmacia & Upjohn immediately ended the partnership. Perhaps NS2710 has been relegated to "veterinary use only". Or perhaps a variation of it will turn out to be GSK"s "new Paxil". By the way ... about those pesky-sounding "allergic reactions" — is that a NeuroSearch-GSK euphemism for some sort of nasty "withdrawal syndrome?" Just thought I'd ask (it never hurts).

For the "disease of depression" GSK and NeuroSearch were, until March of 2002, banking on the success of compound NS2389 which was being hyped as a "triple action", or "mixed monoamine re-uptake inhibitor". Recently though, abnormal cell growth observed in experiments on rats and dogs scuttled further development.

You will probably be hearing much more hype about mixed monoamine re-uptake inhibitors (MMRI's for short) in the near future. In a 2002 interview with the Guardian, a British newspaper, Buus-Lassen spoke of early clinical studies that suggest MMRI's work on some patients who do not respond to "serotonin enhancement" alone. "But we still have to learn and see if this is right," he says. "Until we've had a full program, it's still a kind of prediction. We have many pieces, but we don't know why not all patients are being cured. Several pieces we do not understand." "Cured" did he say? As in cured like Paxil "cures" you? Personally I'm not interested in being "cured" by anything that comes out of a Buus-Lassen lab. How about you?

What Buus-Lassen didn't mention in his interview with the Guardian is the fact that an older class of antidepressants, commonly referred to as "tricyclics", also inhibit monoamine re-uptake. And it was SSRIs (Paxil et al.) that were — according to drug company propaganda — a great leap forward over the tricyclics in both safety and efficacy. We now know this is not true. For example: According to Dr. Robert Temple, Associate Director for Medical Policy United States Food and Drug Administration who (on Monday, September 11th, 2000, during the course of a public hearing conducted under cover of the FDA Pediatric Subcommittee of the Anti-Infective Drugs Advisory Committee) said "....the new antidepressants do not differ in effectiveness from the old antidepressants." So I'm a bit confused: It appears as if GSK and NeuroSearch are simply "recycling" tricyclics — and repackaging them as "new and improved". Triple action, no less! (A toothpaste I buy is also sold as a "triple action" product.)

If you are an drug stocks investor you might be saying "darn!" by now. But not to worry ... GSK-NeuroSearch's NS2359 for the treatment of " Attention Deficit Hyperactivity Disorder", or ADHD, is still alive and kicking. In a number of pre-clinical models, NeuroSearch's scientists claim to have shown NS2359 "improves" the function of the neurotransmitters dopamine, nor-adrenaline and serotonin. On the basis of these pre-clinical (and clinical Phase I results) NeuroSearch anticipates NS2359 will provide a better "therapeutic effect" in the treatment of patients (mostly children) purported to have ADHD.

NS2359 has been tested in 125 healthy volunteers in five Phase I clinical studies, and is alleged to be "well tolerated". In another study involving 54 volunteers (carried out by Professor K. Wesnes, Cognitive Drug Research Ltd.) it was "proven" NS2359 increases attention and improves the ability to recall verbal information. (Could you repeat that?)

NeuroSearch has now initiated a Phase II study with NS2359 at three clinical centers in the U.S. The study includes 100 adult (so called) " ADHD patients", of which 50 be treated with a half milligram of NS2359 once a day, while the other 50 will receive placebo. The stated goal of the study is to gauge the efficacy of NS2359 in the treatment of ADHD symptoms as well as its "tolerability". The treatment period is eight weeks, and the study is expected to be finalized in 2004. Would anyone care to forecast what the results will be? No? Then I will. I predict the NS2359 trials will be reported as a resounding success.

By the way, NS2359 has also been studied in cocaine addicts in collaboration with the United States National Institute on Drug Abuse. What's next? Pediatric cocaine addicts with ADHD?

"Watching Every Neurosearch-GSK (ADHD) Move:
Lilly on the Prowl"
No doubt Lilly is watching this development very carefully, because if NS2359 eventually passes the cursory FDA "sniff test" then its own ADHD drug "Strattera" might have a new competitor to deal with — one backed by GSK's own mega marketing machine.

Strattera, by the way, is a selective nor-epinephrine re-uptake inhibitor (SNRI) — as is another drug targeted by this web site: Effexor. For more company propaganda regarding Strattera visit the Lilly web site where you'll be greeted by three smiling girls leaning on one another's shoulder in a sort of "Norman Rockwell" knock-off pose. (Note: You may have to click "reload" on your browser several times to get the "three girls" image to load.) One presumes they are taking Strattera— and loving it. Or maybe they're just models. In any event: Strattera is approved "by the FDA" for use in children and adolescents, as well as adults.

Adults? Surely by now you've seen Lilly's glitzy 30 second TV Strattera "infomercials" or come across a glossy full-page magazine Strattera ad seeking to educate the public about the "grown up" version of ADHD, Adult "Attention-Deficit Disorder". Visitors stopping by the Strattera web site are provided an " opportunity" to find out if they are "living with ADD" by taking an online "screening test". According to Lilly, many adults have been living with the condition — but don't recognize it. Why? "Because its symptoms are often mistaken for a stressful life". Lilly suggests: "If you've felt this type of frustration most of your life, you may have Adult ADD; a condition your doctor can help diagnose and treat." And after what — a (typical) five minute visit with a physician — one hounded by a Lilly professional sales rep (a.k.a. "detail man") to prescribe Strattera?

"Back to the NeuroSearch-GSK Hydra"
Before we head too far off on a tangent (albeit one that might lead to yet another equally interesting inquiry) let's revisit that corporate Hydra borne of GSK and NeuroSearch: Under the terms of the five-year agreement NeuroSearch will receive some "triple action" funding — a total of EUR 82 million (DKK 610 million) in guaranteed payments from GSK. NeuroSearch will further receive EUR 46.8 million (DKK 348 million), comprising EUR 29.1 million (DKK 217 million) of up-front and research payments, and EUR 17.7 million (DKK 132 million) for 616,000 new NeuroSearch shares to be issued to GSK. The shares correspond to an 8.7% increase of the share capital equal to GSK having a strategic equity interest in NeuroSearch of 8.0% after the capital increase. The purchase price of DKK 214 per share of DKK 20 represents a 30% premium to the average market price over thirty days before the agreement was signed. For new development candidates selected by GSK, the terms of the agreement continue until the patents regarding the selected candidates expires. The agreement may only be terminated by GSK in case of NeuroSearch's insolvency, material breach or in case the controlling interest in NeuroSearch is transferred to a new owner.

Perhaps this deal is, in an oblique manner and after the fact, a way for GSK to say "thank you!" to Buus-Lassen for inventing Paxil which last year earned GSK several billion dollars — just like it has for many years now.

Regarding the GSK-NeuroSearch agreement Dr. Tadataka Yamada, Chairman of Research and Development at GSK, fawned: "Diseases of the central nervous system are particularly debilitating and represent a massive unmet medical need. Combining the skills and resources of GSK and NeuroSearch will accelerate and augment our current efforts to make effective new treatments available to patients as quickly as possible. GSK particularly values the collaborative culture at NeuroSearch, which bodes well for the success of our alliance."

Dr. Yamada, by the way, was one of the top GSK executives deposed in the Donald Shell Paxil homicide/suicide case. (trial exhibits, more depositions and trial transcripts.) Here's just a smattering of what Yamada had to say (about drug warning labels) when questioned under oath by Houston attorney Andy Vickery:

Dr. Yamada: ....We also have the pressure to understand that our drugs aren't safe and that every drug — although every drug — every drug has potential complications but the benefits outweigh the risks.

Andy Vickery: And in that context, what is the importance of proper labeling as a means to accommodate these two competing interests? We need to get this drug out there on the one hand to people but the drug might hurt some people. Can that be ameliorated in some degree by proper labeling?

Dr. Yamada: That is the hope. That is the hope. It's not — It's not always been borne out, and so the FDA is rethinking about what they want to do, how they actually control the physician. I mean one of the problems is that — Maybe I'm saying too much here, Chuck. (Note: "Chuck" is GSK's counsel.)

Andy Vickery: I can't ask you what he said yesterday, but I bet one of them was just answer his questions. But I appreciate your helpfulness.

Dr. Yamada: It's like a pack of cigarettes. You see on there Surgeon General's warning.

Andy Vickery: Right.

Dr. Yamada: Nobody pays any attention to it.

Andy Vickery: Right.

And another excerpt from the Yamada deposition:

Andy Vickery: Dr. Yamada, as a physician, clinician, academician who not only practiced medicine but taught other doctors how to practice medicine for many years, would you agree that as a general proposition that if language appears in the warnings section in boldface that it is more likely that doctors will take heed of that information than if it's put back in the post-marketing surveillance section and it's not in boldface?

Dr. Yamada: Well, my experience would be that doctors just don't look at the label, period. Now, it could be because I was in an academic institution and that's what we did. Maybe we felt that we were more up-to-date and therefore we didn't need no label. I don't know, but my experience is that most physicians don't look at the label very carefully. And I'm not certain — I personally am not certain whether it would make a difference whether something was in a black box or in a warning section or in a precaution section, and if you would ask 20 young physicians, I'm not sure they could tell you the difference between those three.

Andy Vickery: Do you know that in the information disseminating process one of the truly important ways that your company communicates both the indications and the side effects of your medications to doctors is through the — I forget what title we were using about the detail men, as I call them, the people that call on doctors?

Dr. Yamada: Yes.

Andy Vickery: That's a very important conduit for information; isn't it?

Dr. Yamada: I believe it is, yes.

Andy Vickery: And do you know that your people are trained, your salespeople that call on doctors are trained to emphasize and reemphasize information that is in the warning section of the labels to doctors for the very reasons that you talk about?

Dr. Yamada: I believe so, but I don't know for a fact.

Andy Vickery: Okay, sir. How are you doing comfort wise?

Dr. Yamada: I'm fine. I'm fine.

Andy Vickery: Any time you want to take a break —

***

It seems fitting to conclude the history of Paxil by closing with Jorgen Buus-Lassen. The "father" of Paxil. In bed (again) with Boehringer Ingelheim. Now head of his own company, NeuroSearch, and joined at the hip with GSK — which owns Paxil. "I am pleased that we were able to conclude this important strategic alliance with GSK as our two companies have had a well-functioning and trustful partnership within depression research for three years. I have a strong expectation that this extended partnership will be a major success for both companies. This agreement is one of the most important milestones in our history and is a major recognition of NeuroSearch's competencies within research and development. The agreement significantly increases the generation of value in NeuroSearch and strengthens our financial resources considerably."