Pfizer faces criminal charges in Nigeria

You all thought that John Le Carre’s ‘The Constant Gardner’ was fiction did you?

Joe Stephens in the Washington Post writes:

Officials in Nigeria have brought criminal charges for the drugmaker’s alleged role in the deaths of numerous children who received an unapproved drug during a meningitis epidemic, The Washington Post reports. Authorities in Kano, the country’s largest state, filed eight charges this month related to the 1996 clinical trial, including counts of criminal conspiracy and voluntarily causing grievous harm. They also filed a civil lawsuit seeking more than $2 billion in damages and restitution.

The move represents a rare – perhaps unprecedented – instance in which the developing world’s anger at multinational drug companies has boiled over into criminal charges, The Post writes. It also represents the latest in a string of public-relations blows stemming from the decade-old clinical trial, in which Pfizer says it acted ethically.

The government alleges that Pfizer researchers selected 200 children and infants from crowds at a makeshift epidemic camp in Kano and gave about half of the group an untested antibiotic called Trovan. Researchers gave the other children what the lawsuit describes as a dangerously low dose of a comparison drug made by Hoffmann-La Roche. Nigerian officials say Pfizer’s actions resulted in the deaths of an unspecified number of children and left others deaf, paralyzed, blind or brain-damaged.

The lawsuit says that the researchers did not obtain consent from the children’s families and that the researchers knew Trovan to be an experimental drug with life-threatening side effects that was “unfit for human use.” Parents were banned from the ward where the drug trial occurred, the suit says, and the company left no medical records in Nigeria. Pfizer and its doctors “agreed to do an illegal act,” the criminal charges state, and behaved “in a manner so rash and negligent as to endanger human life.”

Aliyu Umar, who served as Kano attorney general until earlier this month says “We realize we are the Third World and we need assistance,” Umar said. “But we frown on people who think they can take advantage of us, especially if it’s for profit. That’s why we decided we needed to take action against Pfizer. Those people responsible should be punished, whether in Nigeria or in the United States, for what they did to our people.”

Le Carre himself said about The Constant Gardner “By comparison with the reality, my story [is] as tame as a holiday postcard.”

Avandia negative data – “Why would you publicize it?” says JP Garnier

More on Glaxo and Avandia – Andrea Gerlin at Bloomberg continues to investigate the drug maker and its latest problem medicine:

Glaxo, Top Ad Spender, Didn’t Publicize Avandia Risks
GlaxoSmithKline Plc was the drug industry’s top advertiser last year [2006], promoting its asthma and diabetes treatments to patients and doctors. Information the company didn’t make well known is now drawing more attention.

London-based Glaxo knew its Avandia diabetes pill posed a risk for heart and circulatory complications as early as 1999, when the medicine won U.S. approval. The cardiovascular concern wasn’t widely disseminated until May 21 [2007] when a Cleveland Clinic Foundation analysis reported that Avandia may cause a 43 percent higher risk of heart attacks than other drugs.

A similar review, begun in 2005 by Glaxo, found that Avandia raised the risk of reduced blood flow to the heart, including heart attacks, by 31 percent. The company gave the review to U.S. regulators and put it on its Web site last year amid more than 2,000 studies. Glaxo says the heart-risk studies, including its own, are flawed and it isn’t obligated, or legally required, to highlight every study done on its drugs.

“Why would you publicize it?,” Glaxo Chief Executive Officer Jean-Pierre Garnier told reporters at the company’s annual meeting May 23 in London. “We don’t publicize every submission we make to the Food and Drug Administration.”

Glaxo, the world’s second-largest drugmaker after New York- based Pfizer Inc., spent $849 million on consumer advertising last year, the most of any pharmaceutical company, according to Nielsen Monitor Plus, a unit of New York-based Nielsen Media Research Inc.

$3 Billion in Sales
Avandia generated $3 billion for Glaxo last year, or 7 percent of total sales, and at least $12 billion since 1999. Analysts had estimated sales of $4 billion in 2007. The medicine helps the body better use insulin to lower high blood sugar, which in excessive amounts can cause complications such as heart disease, and kidney and eye damage. Glaxo says the treatment has risks similar to other oral diabetes medicines.

By 2005, the drugmaker had spent almost $200 million on advertisements advising U.S. consumers to ask their doctors about Avandia, its second best-selling product. Advertising included warnings contained in prescribing information, such as “Avandia may cause fluid retention or swelling, which can make some heart problems worse or lead to heart failure,” from a 2005 television commercial.

The Cleveland Clinic report released in the New England Journal of Medicine has caused Glaxo shares to decline 12 percent since then, cutting 9.94 billion pounds ($19.7 billion) from the company’s market value. Glaxo shares fell 18 pence, or 1.4 percent, to 1292 pence in London, the lowest price in two years.

“It’s fair to say that from early on there have always been a few events of cardiovascular nature,” Glaxo Chief Medical Officer Ron Krall said May 21.

Call for Research
As far back as April 1999, executives of SmithKline Beecham Plc, which a year later merged with GlaxoWellcome Plc to become GlaxoSmithKline Plc, told the FDA that Avandia caused “minimal” cardiovascular side effects and “mild to moderate” fluid buildup. Fluid in the lungs or bloodstream can increase the heart’s workload.

The agency cleared the drug for sale the next month. Some advisory committee members called for more research on potential complications.

In February 2001, after the drug was on the market, Glaxo agreed to an FDA request to change the drug’s prescribing label to warn doctors that Avandia, like other drugs in its class, can cause fluid retention.

Company sales representatives who knew the risks “denied their existence” three months later in oral presentations at the American Association of Clinical Endocrinologists’ meeting in San Antonio, Texas, FDA officials noted in a July 2001 letter to Glaxo.

FDA Criticism
The FDA told Glaxo in that letter that its marketers should stop denying or minimizing the increased risk of “heart failure or other cardiovascular adverse events” in patients taking the drug with insulin, according to the FDA’s Web site. The agency criticized Glaxo for continuing to “engage in false or misleading promotion of Avandia.”

Analysts at Citigroup Inc. and Morgan Stanley had noted possible cardiovascular side effects in notes to investors last year.

“The key issue in addition to at least equivalent efficacy of Avandia to metformin and glyburide is cardiovascular safety,” Citigroup analysts wrote in a Nov. 23 report.

The next month, as results of a large-scale, company-funded trial were published, Glaxo executives said the overall risk of death, heart attack and stroke with Avandia was similar to other diabetes medicines.

`We Can’t Deny’
Diabetes researcher Rury Holman of Oxford University in the U.K., an investigator in the $100 million company study, known as ADOPT, said in a Dec. 3 interview that the results would cause concern.

“These people are early diagnosis, they haven’t got complications,” Holman said. “The fact that we’re seeing these cardiovascular effects in them, we can’t deny that. The concern when these data come out is you’ve got relatively healthy patients and still there’s a little bit of a signal.”

Earlier this year, cardiologist Steven Nissen and co- researcher Kathy Wolski of the Cleveland Clinic found Glaxo’s own analysis of Avandia studies while scouring the company’s Web site. The two uncovered the analysis after failing to gain the company’s cooperation for their review, Nissen said in an interview May 23.

“I just built this piece by piece until I had enough,” Nissen said. “Then I stumble upon the company’s own meta analysis deeply buried on their Web site, and it shows the same thing. It was a eureka moment for sure.”

Glaxo Responds
Earlier this week, Glaxo began a campaign to challenge Nissen’s findings that helped its stock recover. Chris Viehbacher, the president of Glaxo’s U.S. pharmaceuticals unit, met with reporters May 30 to take exception to the report and the “sensationalizing” of it in media coverage. Krall wrote a May 30 letter to the U.K. medical journal The Lancet which the company said “clarifies the safety record of Avandia.”

Since 1999, the company and the FDA have monitored and updated Avandia’s label for adverse events and continue to do so, the company said today in an e-mailed statement.

“The totality of data provide clear evidence that Avandia has a comparable cardiovascular profile to other oral diabetes medicines and that these data are more scientifically rigorous and more clinically meaningful than the recently published meta analysis,” Glaxo said in the statement.

The company’s failure to place as much emphasis on Avandia’s risks as it placed on the drug’s benefits may hurt it because of possible legal liability, Morgan Stanley analysts led by Andrew Baum said May 21 in a note. Avandia is facing competition from newer treatments, and reports of a heart risk may hurt sales by as much as 50 percent, analysts estimate.

GlaxoSmithKline’s “robust defense of Avandia safety and their conduct comes with a high risk if evidence of poor disclosure subsequently emerges,” Baum wrote.

To contact the reporters on this story: Andrea Gerlin in London at agerlin@bloomberg.net Michelle Fay Cortez in Minneapolis at mcortez@bloomberg.net