How deadly drugs like Prozac pass through the approval process and become “blockbusters”
The sordid tale I’m about to share with you centers around two key players.
The first is US drug giant Eli Lilly who, just like the rest of its Big Pharma ilk, loves to shower us with self-aggrandizing sop about what a wonderfully altruistic outfit it is.
“A medicine company that puts health above all,” is how Lilly describes itself.
A cursory examination of Lilly’s corporate rap sheet reveals otherwise. Just since 2000, Lilly has amassed a hefty $3 billion in criminal and civil penalties. The bulk of these fines arose due to unapproved promotion and false claims for its drugs, health insurance fraud, and offences under the Foreign Corrupt Practices Act.
Eli Lilly, in other words, is a serial corporate criminal whose record indicates it puts profits above all else.
By the way, that $3 billion of penalties resulted from government prosecutions. As you’re about to learn, attempts by regular citizens to bring this pharma behemoth to justice have not been nearly as successful.
Lilly’s biggest fine, in 2009, came from pimping its antipsychotic drug Zyprexa for unapproved uses. However, its best known drug is fluoxetine, the toxic and suicide-inducing poison known to most people as Prozac. This blockbuster SSRI was unleashed on the American public in 1988. By July 1991, the FDA had received over 14,000 reports of patients who suffered adverse effects while taking Prozac. At the time, this was by far the highest number of complaints made for any medication.
Relentlessly promoted in popular culture as a “happy pill”, Prozac is quite the nasty drug.
The Wesbecker Mass Murder-Suicide Case
The first big Prozac case to go to court centered around Joseph Wesbecker who, after being prescribed Prozac, opened fire with an AK-47 at the Standard Gravure printing plant in Louisville on September 14, 1989. After killing eight fellow workers and wounding 12 others, he turned the gun on himself and committed suicide.
Survivors and relatives of those killed took Lilly to court in 1994, arguing that Prozac was instrumental in triggering Wesbecker’s horrific meltdown.
Wesbecker’s condition clearly deteriorated after commencing Prozac. However, the case was not a slam dunk due to Wesbecker’s troubled history. Once considered a conscientious and hard worker, relations with his superiors had soured dramatically after a change in management. The company had also downsized, asking more work from fewer employees. Before being prescribed Prozac, Wesbecker had also experienced two failed marriages. As the strain began to overwhelm him, he was voluntarily hospitalized for mental problems and even tried to commit suicide.
So the problem for the plaintiffs was that Lilly’s lawyers would seize upon the shooter’s disturbed past in their quest to absolve Prozac.
The problem for Lilly, meanwhile, was that Prozac’s ability to induce suicidal behaviour was not mere speculation but an observation published in the peer-reviewed literature. Prozac’s record-breaking form for triggering adverse event reports didn’t exactly help either.
Prozac Kills
Lilly knew damn well their superstar drug was dangerous. Like other SSRIs, the drug has solid form for causing restlessness, agitation, and a most unpleasant state called akathisia - an intense feeling of inner restlessness and an uncontrollable need to move that can cause anxiety and distress.
The last thing you want to do to a depressed person is put them in an agitated state. Depressed people often feel like life is not worth living, but thankfully most do not act upon suicidal thoughts. Putting them in an agitated and restless state, however, is akin to fixing a supercharger to their negative thoughts. Akathisia caused by antipsychotic drugs has long been recognised as a trigger for suicidal and homicidal-suicidal feelings.
Lilly’s own internal documents show akathisia triggered by Prozac was identified as early as 1978. On August 2 of that year, when only three trials were under way, minutes of a meeting of the Fluoxetine (Prozac) Project Team reported:
“There have been a fairly large number of reports of adverse reactions... Another depressed patient developed psychosis... Akathisia and restlessness were reported in some patients.”
A similar meeting 10 days earlier had noted “some patients have converted from severe depression to agitation within a few days; in one case the agitation was marked and the patient had to be taken off [the] drug.”
On May 25, 1984, according to Lilly’s internal documents, a letter from the German licensing authority, the Bundes Gesundheit Amt (BGA), stated:
“During the treatment with the preparation [Prozac], 16 suicide attempts were made, two of these with success. As patients with a risk of suicide were excluded from the studies, it is probable that this high proportion can be attributed to an action of the preparation.”
In other words, an unusually large number of participants in Lilly’s Prozac trials were attempting suicide, and Lilly’s standby excuse that the fault lay with their depression and not Prozac just didn’t cut it.
In January 1985, the Germans told Lilly they would not license the drug, citing “suicidal risk” as one of the reasons. Lilly’s scientists continued trying to persuade the BGA, but focused most of their efforts on the US. During the US licensing process, Lilly did not tell the FDA of the German concerns.
And despite what they knew about fluoxetine, the BGA eventually allowed Prozac to market on the proviso it carry a warning, stating there was a “risk of suicide”. Despite resistance from Lilly, the warning finally appeared on the German package insert in 1992.
While all this was going on, the company conducted a sustained campaign to diminish the idea Prozac could induce violence or suicide. In response to criticism emanating from the UK, a February 7, 1990 internal memo from from Leigh Thompson, one of Lilly’s chief scientists, warned:
“Anything that happens in the UK (England) can threaten this drug (Prozac) in the US and worldwide. We are now expending enormous efforts fending off attacks because of (1) relationship to murder and (2) inducing suicidal ideation.”
Another memo from Thompson that same day revealed just how high the stakes were for Lilly:
“I am concerned about reports I get re UK attitude toward Prozac safety … I hope Patrick [probably a Lilly employee, but not identified fully in the memo] realises that Lilly can go down the tubes if we lose Prozac, and just one event in the UK can cost us that.” (Bold emphasis added)
We see here a senior Lilly executive stressing that Lilly could “go down the tubes” if Prozac’s deadly attributes became common knowledge.
Lilly desperately needed the world to remain oblivious to Prozac’s harms and instead keep subscribing to the nonsensical “Listening to Prozac” fluff of people like Peter Kramer.
Eli Lilly, therefore, had a lot riding on the hallmark Wesbecker case.
The plaintiffs also had a lot riding on the case. Which begged the question as to why their lawyer, Dallas attorney Paul Smith, did such a lackluster job in court.
His lame duck performance led to a close jury decision in favor of Lilly.
Presiding judge John W. Potter smelled a rat, and toward the trial’s conclusion asked both sides if they’d made a secret settlement. Both sides denied it.
Some months later, Potter’s suspicions were confirmed. During a divorce hearing involving one of the plaintiffs in the case, it was revealed he was expecting a substantial payment from Lilly. The close jury decision in Lilly’s favor, it turned out, was the result of collusion between plaintiffs and defendant. Lilly had secretly given a huge sum of money to Smith and his clients in return for him presenting a watered-down case to the jury.
A disgusted Potter threw out the jury verdict and changed it to a settlement with prejudice by Eli Lilly and Co.
Incredibly, both Smith and Lilly then had the gall to appeal Potter’s decision with Kentucky’s Court of Appeals – not because they denied rigging the outcome, but on the grounds that Potter did not have the power to reverse his original decision. Sickeningly, the appeals court concurred and ruled against Potter, arguing he no longer had jurisdiction.
The case was then appealed to the Kentucky Supreme Court which, on May 23, 1996, decided unanimously in favor of Judge Potter.
The amount of the secret settlement was never revealed by Lilly or Smith, but in 2000 the Indianapolis Star reported an amount of $20 million - an amount subsequently confirmed by two of the plaintiffs in 2019.
So that’s an intro to Eli Lilly - an entity only too willing to get down and dirty in its pursuit of profits.
The other key figure in this story is the late John Virapen, a former senior Eli Lilly sales manager who passed away in 2015 from diabetes complications. From 1979 to 1988, Virapen worked for Lilly affiliates in Copenhagen and Stockholm, becoming Swedish national manager in 1982. After falling for a Puerto Rican woman, in early 1988 he assumed the position of Lilly’s Director of Pharmaceutical Marketing for Puerto Rico. However, after only six weeks, his employment was unceremoniously terminated.
According to court summaries, Lilly claims to have fired Virapen due to his “failure to act within Lilly’s norms, philosophy and practice, as well as his disrespectful behavior towards his subordinates and peers.” No further information about Virapen’s alleged behavior can be gleaned online, but it does seem odd that someone with the company for almost a decade, who rose to be a star salesman and manager, suddenly forgot how to “act within Lilly’s norms, philosophy and practice.”
Virapen - born in Guyana to Indian-descended parents - proffered an alternative explanation, which formed the basis for a lawsuit against the company. He alleged the real reason he was fired by Lilly was because of racial and age discrimination.
Before moving to Puerto Rico, Virapen said he was informed by several Lilly US executives at a training course in Indianapolis that Puerto Ricans did not like Indians. After being in Puerto Rico for one month he was allegedly told by Robert Barkei, Lilly’s International Area Director, “I don’t like you.” He further stated in his evidence he was told “the Indians are taking over” in reference to the appointment as General Manager of Andrew Mascarenhas, an Indian native.
In any remotely competent company, poor job performance would be the subject of discussions with the allegedly errant employee, and possibly lead to reprimands and ultimatums. However, Virapen stated Lilly never discussed with him the alleged incidents which led to his dismissal - a claim the court acknowledged “is buttressed by the fact that no evaluation reports exist as to his performance due to his brief six-week tenure at Lilly.”
On the face of it, to this jaded observer of Big Pharma shitefookery, Virapen’s story seems the most plausible. However, in this David vs Goliath battle, the courts sided with Goliath and dismissed Virapen’s case and subsequent appeal.
The Sordid Truth Starts to Emerge
In 2007, with no love lost between Virapen and Lilly, the former testified against the latter in a lawsuit brought by Georgia widow Dawn Porter. She contended Lilly was responsible for the suicide of her husband, Leland “Lee” Porter, because it failed to adequately warn of Prozac’s potential risk for suicide.
Under Georgia law, Porter was required to prove that, but for the alleged inadequate warning, her husband’s physician would not have prescribed Prozac to decedent.
Unfortunately, Lee’s physician was one Bernard Behr Wolfberg, a physician board-certified in psychiatry who, judging by Internet search results, is still practicing in Georgia.
Wolfberg stands as a striking testament as to why you should do your own research before mindlessly gulping down anything prescribed by your doctor. Wolfberg acknowledged he wasn’t familiar with much of the literature concerning SSRI-induced suicidality in adults and did not recall what the Prozac label said about suicide risk in July 2003.
Nevertheless, he maintained he did not regard Lee Porter as a suicide risk and that the treatment he gave was appropriate based on what he knew at the time. He unequivocally testified that even if he had received the warning that Porter claimed Lilly should have provided, he still would have prescribed Prozac.
Instead of being kicked out of medicine as a menace to patients, Wolfberg’s testimony was embraced by the court and proved fatal to Porter’s failure-to-warn claim on causation grounds.
Lilly once again avoided culpability for the effects of a drug it knew early on was potentially deadly.
Virapen had been brought to testify in Porter’s case by her lawyer, Andy Vickery. His testimony regarded his inside knowledge of Prozac and Lilly’s dubious behaviour, especially when it came to marketing and obtaining regulatory approvals.
And Virapen knew plenty.
Disappointed by the outcome, and realizing his testimony would be buried along with the Porter case, Virapen became more vocal in his criticism of Lilly. He began spilling the beans on his former employer by writing a number of books, including Side Effects: Death. Confessions of a Pharma-Insider.
Selling Your Soul to the Pharma Devil
Virapen was born in Guyana in 1943. After a childhood marred by poverty, racism and sexual abuse at the hands of a priest, he migrated from his homeland while still in his teens. After meeting a Swedish girl in London, he eventually married and settled in Sweden. It was there, in 1968, that he began working as a sales representative for a series of smaller pharmaceutical companies.
Virapen quickly proved himself to be a gifted salesperson. He embraced the drug industry practice of building profiles on all the doctors he visited, learning not only what types of patients they catered to and what type of illnesses they were most likely to encounter, but also their birthdays, marital status, number of children … even their favourite hobbies, wines, cars and music.
“You create a psychological profile,” wrote Virapen, “That’s part of the technique, the craft.” This profiling allowed pharma sales reps to befriend and bond with doctors, breaking down any resistance or skepticism they might have towards the products they were being offered.
The “craft” even extended to having affairs with secretaries in order to get closer to doctors. Virapen’s extramarital sales techniques eventually led to the breakdown of his first marriage.
In 1979, Virapen was offered a job at Eli Lilly’s Nordic division, and two years later was appointed the company’s Swedish sales manager. “Sweden,” according to Virapen, “was Eli Lilly’s Achilles’ heel. It had a low level of awareness, hardly any product acceptance and meager sales figures.”
Virapen promptly turned things around. Between 1981, the year he was appointed national sales manager, and 1988, Lilly’s Swedish sales increased more than twenty-fold. An internal appraisal declared Virapen the company’s high-flying “Achiever” and he was appointed General Manager of Eli Lilly & Company in Sweden. Along the way, Virapen also attained a degree in medicine and a PhD in psychology.
Virapen developed and implemented marketing campaigns for what he later admitted in his memoirs to be “dangerous and widely-used” drugs. Lilly’s ample resources meant he had an extensive arsenal at his disposal, including:
-‘Scientific’ conferences that in reality were marketing sessions for Lilly’s products.
-Expensive gifts to doctors, while “opinion leaders” were given free trips and payments for authoring supportive journal papers.
-Brothel visits awarded to “particularly high-maintenance” clients. As an illustrative example, Virapen described a trip in which Lilly flew a group of doctors to Singapore. The trip “was officially called training,” said Virapen, who then quickly dismissed any notion Lilly really flew a group of sun-starved physicians half-way around the globe just to have them sit in seminar rooms for two weeks.
“No, the men were supposed to have fun, and that’s what they got. The beach wasn’t far, the brothel and the casino weren’t far either. We saw to it that it was a superb experience.”
The purpose of such trips was to cultivate a fraternal “what happens in Vegas, stays in Vegas” bond between the Lilly reps and the physicians. “And it worked,” said Virapen; “the physicians we’d invited gladly remembered us and always had an open ear when our representatives paid a call. They marketed our products to their patients.”
Plying doctors with prostitutes was hardly the only salacious activity Virapen used to push Lilly’s wares.
“[B]ribing authorities,” admitted Virapen, “also became a part of my sad repertoire.”
One of these bribery cases would turn out to be the defining event of his career. “It was the bribing of an independent expert,” revealed Virapen, “employed by the regulatory agencies of a country, to gain approval of a drug.”
That “flagship” case would prove to be the one from his eventful 35-year career that he said later tormented him the most. “I had performed a criminal act,” acknowledged Virapen. Not only that, but under pressure from his employer, he says he used bribery to “influence drug approval, even though I knew the drug would harm people.”
That drug was fluoxetine.
A Drug So Safe and Effective You Have to Lie and Bribe to Get it Approved
When Lilly began petitioning regulatory agencies around the world for approval of fluoxetine, the company was still recovering from the benoxaprofen saga. A non-steroidal anti-inflammatory drug (NSAID), benoxaprofen first appeared on the European market in 1980 under the name Opren. In May 1982, it became available in the US as Oraflex.
Launched with a barrage of fanfare and exaggerated claims, benoxaprofen was set to become Lilly’s next blockbuster. One US industry analyst predicted Oraflex would reach annual sales of $250 million by 1985 and become a go-to drug for the country’s large and growing population of elderly arthritis patients.
Then the poo-poo hit the fan.
Only ten weeks after its US release, benoxaprofen was pulled from pharmacy shelves after US and UK authorities received thousands of adverse event reports, including the deaths of over 70 people, mostly from liver and kidney failure.
Lilly, in typical drug industry fashion, went into denial mode. ‘’We were convinced - and we remain convinced - that the drug is safe and effective when it is used properly,’‘ claimed Eugene L. Step, president of Lilly’s Pharmaceutical Division, shortly after the withdrawal. He asserted that sales of the drug were suspended in an “environment of hysteria.”
Turns out the “hysteria” was well-founded. As Virapen planned his marketing efforts for benoxaprofen in Sweden, he’d heard rumors of problems in the pre-marketing clinical trials for approval in Denmark. “Harmful side effects became apparent, which most notably affected the kidney and liver.”
But it was not until August 1985 – three years after the drug was withdrawn – that Lilly finally admitted to an Indianapolis courtroom it knew full well of the adverse events and deaths in Britain, but failed to disclose them when seeking FDA approval. It even launched a multi-million dollar marketing campaign upon gaining the May 1982 approval, which included 6,100 press kits that the even the pharma-friendly FDA deemed “false and misleading.”
Despite Lilly’s nefarious behavior and the unnecessary deaths it caused, the company received a negligible penalty. The drug giant received a mere $25,000 fine, while its former chief medical officer Ian Sheddon (who had since moved over to Glaxo Pharmaceuticals in the UK) was fined a similarly paltry $15,000. He could have faced up to fifteen years in prison, reported New Scientist, but it seems the court took into account a congressional committee’s conclusion that “Lilly’s failure to make such reports appeared consistent with current industrial practice.”
Everybody does it, so what’s the big deal, right?
The only cause for concern, it seemed, was Lilly’s share price and future earnings potential. After the benoxaprofen withdrawal, the company’s share price slipped 20% and analysts predicted the company was facing a major retrenchment with lower earnings and slowed growth.
Given the pressure by investors to protect future earnings, and the laughable ‘penalty’ imposed upon Lilly for its deceitful behaviour, it is hardly surprising the company embarked on a similar cover-up during the approval process for its next blockbuster: Prozac.
Getting a Bad Drug Approved
As general manager for Eli Lilly in Sweden, it was Virapen’s job to ensure fluoxetine attained regulatory approval in that country. He and his team began by showing some Swedish psychiatrists a selection of data for fluoxetine. When told that Lilly planned to seek approval for the drug in Sweden, the psychiatrists laughed and shook their heads. Virapen quickly realized he had a problem. He’d heard rumours circulating that the fluoxetine clinical studies “simply hadn’t been good enough.” Now here was a group of psychiatrists who thought Lilly’s plan to seek approval for this questionable drug was so foolish they couldn’t help but break into laughter.
But there was no turning back. Desperate to recover from the benoxaprofen fallout, Lilly forged ahead, undaunted.
After an internal company seminar in London, Virapen shared a limousine to the airport with none other than European Lilly head, Sidney Taurel. After what proved to be a tense ride, Virapen emerged with the realization his career depended upon the approval of fluoxetine in Sweden. The pressure on Virapen increased when he learned one of the experts assigned by the Swedish regulatory authority to review fluoxetine was none-too-impressed with the drug. She was an accomplished psychiatrist who had performed research with fluoxetine. However, her research involved only 5 milligram dosages, which she believed to be the absolute maximum in view of the drug’s risks. Lilly, on the other hand, had applied for approval of 20 milligram doses.
To compound Virapen’s woes, Taurel had paid him another visit and ominously advised him to “Think about your career.”
Virapen had to think of something, and urgently. One night, a Machiavellian idea came to him.
When a drug company submitted clinical trial data to the Swedish authorities as part of the approval process, the data would first be evaluated by an independent expert. That expert conducted the preliminary work for the agency, performing the formidable task of analyzing and deciphering the columns of data, one by one. To ensure the independent expert remained independent, his identity was kept from the company making the application.
But what if Virapen could uncover the identity of the independent evaluator?
“If we knew who he was,” explained Virapen, “we could create a profile for him. We could find out how high the threshold was, which we had to cross, to cut a deal with him.” Virapen went into detective mode and soon learned, based on qualifications and status, that only one of five doctors in Sweden could be the independent expert. One by one, Virapen and his colleagues whittled down their list until they had their “Mr. Unknown,” a psychiatric professor from the west coast of Sweden.
The courting of Mr Unknown consisted of two restaurant dinners. During the first, the professor told Virapen he didn’t like fluoxetine at all. But the two got along well and Virapen sensed he had an opening. “He was an asshole and I was one too,” said Virapen, “so we fitted like a glove.” At the second dinner, Virapen felt comfortable enough to ask Mr Unknown what it would take for him to give fluoxetine his stamp of approval.
According to Virapen, the reply from this fellow asshole was: “Money is always useful”.
The next day, Virapen says he called Lilly’s northern regional head office in Copenhagen and told them it would cost 100,000 crowns to get a “speedy” approval for fluoxetine in Sweden. At the time, this was equivalent to around US $20,000. After consulting with the Lilly office in Geneva, the Copenhagen director called him back the following day. “John, do whatever you think is necessary. We won’t put any obstacles in your way.”
When Virapen met with Mr Unknown to give him the good news, he was met with an extra surprise demand. Mr Unknown was additionally demanding he and his colleagues receive a Lilly-funded research assignment for fluoxetine - the same drug he had laughed and “snootily” shaken his head at only two weeks earlier. The research grant Mr Unknown was seeking would provide him and his colleagues with a lucrative income stream for years to come.
Even Virapen was taken aback by the newly corrupted psychiatrist’s audacity. But Lilly wasn’t fussed. It had to award someone with the contract anyway, and with Mr Unknown they at least knew the results would be favorable.
Mr Unknown clearly had no scruples, which was just what Lilly needed. He worked the data like a masseuse, shuffling the statistics in a way that made fluoxetine seem far better than it was. Deaths disappeared in small footnotes, and suicides were re-labelled with far more benign descriptors such as “miscellaneous effects.” As a finishing touch, he even added his own personal letter of recommendation.
Shortly after Mr Unknown submitted his fraudulent analysis, Virapen was asked to contact the state authority responsible for pharmaceutical pricing. They wished to commence price negotiations for fluoxetine. This was welcome news to Virapen, as such requests meant the drug was close to being approved. During the negotiation, the affable Virapen and his officious, seemingly uncompromising female colleague worked the state official with a good cop, bad cop-style performance. According to Virapen, it worked a treat because he came away with the favourable price he was after: $1.20 per 20 milligram dose.
The unexpected twist to this story is that, despite the willingness of Dr Unknown to prostitute himself and write up a glowing report for fluoxetine, the Swedish authorities initially refused to give approval to fluoxetine. The drug faced an insurmountable roadblock in the form of the regulatory board member and highly respected scientist who maintained fluoxetine should be limited to 5 milligram dosages. She had stuck to her guns and flatly refused to approve a 20 milligram dose unless a 5 milligram dose was concomitantly approved. Lilly would have none of that, as a 5 milligram dose meant a 75% reduction in the revenue they were hoping for. Agreeing to a 5 milligram dose would have also set an unfavourable precedent for other regulatory agencies around the world.
Given all that had transpired thus far, one would assume the failure to get approval for fluoxetine in Sweden greatly disappointed Virapen and his Lilly colleagues. It turns out, according to Virapen, they were delighted. While fluoxetine would not be sold in Sweden, the successful price negotiations set a precedent for negotiations in other countries. “And in that regard,” wrote Virapen, “it had all been worth it. Fluoxetine became a large commercial success – especially in the United States and Great Britain – like there had never been before in the history of the pharmaceutical industry, using the 20 mg dose and ‘my’ price.”
In September 1995, fluoxetine was finally approved for sale in Sweden in both 4 and 20 mg doses, marketed under the name Fontex.
According to Läkemedelsvärlden, a Swedish medical and pharmaceutical news publication, the actions of the National Board of Health and Welfare’s external expert - the man dubbed by Virapen in his book as “Mr Unknown” - were investigated by Swedish prosecutors in 1995, who determined his role as an external consultant was not covered by the bribery laws in effect at the time. He could therefore not be held accountable for his actions. Läkemedelsvärlden reports Swedish law was amended in 1999 as a result of this case; today, such conduct would have been a criminal offense.