We may as well milk it while we can: Zyprexa and prescription drug reform

Here's a victim’s name and face for the prescription drug reform issue. It's a story of cherry-picked studies, aggressive marketing to doctors by pharma salesmen bearing gifts, and an ultimately fatal side effect of Zyprexa:

His prom photo showed he was a handsome teenager with a messy mop of dark brown hair. He went to college to study political science. But within the next year or two John Eric Kauffman developed mental illness--a severe form of bipolar disorder. In 1992, in his late twenties, he suffered his most severe psychotic breakdown. Over the next 8 years, he didn't suffer any psychotic breakdowns, thanks to lithium and Stelazine. After that, a psychiatrist changed his medications, John stopped taking them, his condition worsened, and he was hospitalized. In the hospital he was given Zyprexa in a relatively high dose. He then remained on Zyprexa for 6 years, and gained 100 pounds, developing heart disease. John's weight gain probably contributed to her son's death in his forties from an irregular heart beat, according to a forensic pathologist. (NY Times, 1/5/07). More of John's story can be found here.

Drug maker Eli Lilly had done studies. But tens of thousands of lawsuits contend that Lilly did not fully disclose risks it discovered during studies conducted to get FDA approval for Zyprexa, risks that became more apparent in the years after the drug hit the market.

The preapproval studies lasted six weeks, not nearly time for diabetes to manifest itself, plaintiffs' attorney Joseph Saunders says, but there were red flags. Some 29% of participants gained significant amounts of weight. Rapid weight gain puts people at higher risk of developing diabetes.

Lilly paid $1.2 billion to settle 30,000 claims. And Lilly has more than private attorneys to worry about. Nine states have sued, claiming the company illegally promoted unapproved uses of Zyprexa and downplayed its side effects. The states want to be reimbursed hundreds of millions for Medicaid dollars they paid for Zyprexa.

In 2003, the FDA directed that not only Zyprexa, but all atypical antipsychotics carry a warning about increased risk of hyperglycemia and diabetes.

Lilly continued to market its drug as more effective but no more dangerous than its competitors. Only in Fall, 2007 did the company agree to change Zyprexa's label to state that its tendency to increase blood sugar levels, another diabetes risk factor, is higher than its competitors.

Asked Saunders: "Why did it take 10 years to warn people about something they knew from their clinical trials?"

In the meantime, Eli Lilly marketed Zyprexa aggressively to doctors. Here's a confessional story of one Zyprexa salesman, Shahram Ahari:

Salesmen wooed doctors with free samples, treated them to expensive dinners and paid them to give speeches at seminars.

"It practically sold itself," said Ahari, who sold Zyprexa in New York from 1998 to 2000.

The gravy train hit some bumps. Reps started hearing from doctors concerned about patients "blimping up." Competitors hammered them on it, derisively twisting Zyprexa's generic name, olanzapine, into "olanza-pig."

The Zyprexa sales reps eagerly awaited word from Lilly's brand team on how they should deal with the weight/diabetes issue. Ahari says this is what they came up with: Tell doctors to instruct patients to drink a glass of water before and after they eat, to suppress appetite.

"We'd have to do it with a straight face," Ahari said, "and after a while, it just became uncomfortable."

With doctors he knew well, he said his pitch was blunt: "Would you rather have a skinny, unwell patient or a fat, stable one?"

Doctors started reporting patients developing diabetes. "That was a big, scary thing," Ahari said. If the FDA required that Zyprexa carry a black box warning about diabetes, "it would have been death, market-wise."

He says sales reps were instructed to deflect the issues of weight gain and diabetes. "We were taught to downplay it and negate it, or to change the topic."

Lemons, the Lilly spokeswoman, says the company can't be certain what every sales manager told their sales reps, but "that has never been our corporate policy." She questioned Ahari's objectivity because she said he is now a paid witness for trial attorneys taking on pharmaceutical companies. Ahari says he was a paid witness in just one case, which was about preserving the confidentiality of physicians' prescribing patterns.

Like many critics, Ahari came to feel Zyprexa was effective, appropriate for many people. But he believed that the brass at Lilly downplayed the weight and diabetes problems because the clock on the patents was ticking. The thinking was, "we may as well milk it while we can." (St. Petersburg Times, 12/16/07)

Advice: Urge your government health watchdog agencies to require doctors to disclose their research funding, and require pharma companies to allow doctors to publish whatever results they see fit.

Thanks to Helen Haskell, NY Times reporter Alex Berenson, and St. Petersburg Times reporter Robert Farley.