The Torturous Tale of Anemia Drugs: How Many People Did They Harm?

Three anemia drugs–Epogen, Procrit and Aranesp–have generated more than $8 billion in U.S. sales. Epogen became the single costliest medicine under Medicare, and taxpayers shell out as much as $3 billion a year for these drugs.

A growing body of research has shown that the drugs’ benefits, including quality-of-life issues such as “happiness,” are seriously overstated. Worse, according to a long story in The Washington Post, their potentially lethal side effects, including cancer and strokes, were long overlooked.

Anemia occurs when the body produces too few red blood cells, which carry oxygen from the lungs to the rest of the body. The drugs are artificial versions of a natural hormone called erythropoietin, which stimulates the body to produce red blood cells. Before the drugs’ advent, patients were given transfusions of red blood cells, a cumbersome process that can take hours.

Epogen and Procrit were approved by the FDA in 1989 for patients with kidney disease. Amgen manufactured both; Procrit was licensed by Johnson & Johnson. Amgen’s Aranesp was approved in 2001.

Last year, an 84-page Medicare research study determined that among most kidney dialysis patients, who compose the drugs’ largest market — the kidneys are where the natural hormone is made — there was no solid evidence that they made people feel better, improved their survival or had any “clinical benefit” except a higher red blood cell count. As The Post said, “It was a remarkable finding of futility: While drugmakers had seen billions in profits over 22 years, much of it from taxpayers, millions of patients had been subjected to dangerous doses that might have had little advantage.”

One of those patients was Jim Lenox. On the day the frail cancer patient received his last injection in 2008, he was awaiting discharge from the Baltimore Washington Medical Center. Then a nurse said he needed another dose of anemia drugs.

His wife, Sherry, wondered why, because his blood readings had been close to normal. But the Lenoxes deferred to the professionals and accepted an injection of Procrit, which his cancer clinic normally billed for $2,500 each.

Hours later, Lenox was dead.

The story behind the anemia drugs is long and complicated, and illustrates how the financial incentives that are integral to the U.S. health-care system contribute to its inefficiency and lethal potential. We wrote about this smarmy situation last year.

Drug trials conducted by both Amgen and Johnson & Johnson missed the dangers and promoted the benefits that years later would be deemed unproven. The companies took more than a decade to fulfill their research commitments. And when bureaucrats tried to curb the largest doses, Congressional lobbyists were successful, and regulators opened the spigot.

The fault of dangerous drugs being promoted on the open market is shared by doctors, clinics and hospitals, whose budgetary pressures contribute to a “more is more” philosophy. The more they treat, the more they earn, the bigger the dose, the bigger the payoff.

Unlike medications you fill at a pharmacy, drugs administered by physicians, such as the anemia group, can be profitable for them.

Big Pharma offered doctors incentives to give large doses and they offered volume discounts. Most critical, The Post says, was the lobbying pressure, under which Congress and Medicare administrators forged a system in which doctors and hospitals were reimbursed more for the drug than they paid-as much as 30 percent, according to the Medicare Payment Advisory Commission, a group that advises Congress. The markup on patients covered by private insurance was even larger.

At the peak of the drugs’ use in 2007, more than 8 in 10 Medicare dialysis patients were receiving the drug at levels higher than the FDA now considers safe, according to federal statistics. (Other patients got the drugs, but records kept on dialysis patients are better.)

“An oncologist could make anywhere from $100,000 to $300,000 a year from this alone. And all the while they were told that it was good for the patient,” Charles Bennett, from the Medication Safety and Efficacy Center of Economic Excellence at the University of South Carolina, told The Post.

During his cancer treatment, Jim Lenox was given Aranesp several times at a clinic. The insurance company reimbursed it about $900 for each, although the clinic would have paid about $600.

The profit margin for Amgen was far higher than the industry average. Much of it came from the pockets of taxpayers. A Washington University professor of medicine who had been paid by Amgen to promote the drug, called its success “a paradigm for the pharmaceutical industry.” He later turned critic after Aranesp’s dangers became known while Amgen continued to promote higher doses.

Both companies declined the paper’s requests for interviews and claimed that their primary interests were serving patient needs and providing consumer information.

The market expanded to nearly all dialysis patients, not just the estimated 16 in 100 who require blood transfusions, and the size of the average dose more than tripled. The FDA approved the drugs to treat anemia in cancer and AIDS patients, as well as those getting hip and knee surgery.

The drugmakers agreed to conduct safety studies, but the full results were never published. Amgen filed a “clinical study report” with the FDA in 1995, claiming its research commitment was fulfilled. The FDA did not deem the study completed until March 2004, almost 15 years after the company agreed to conduct it.

Another study in conjunction with the drugs’ approval was supposed to have 400 patients. Eleven years after initiating it, Johnson & Johnson said it was having difficulty recruiting enough, so statistically significant conclusions were elusive. And the FDA said significant amounts of data were missing.

With FDA approval, Johnson & Johnson halted the study in 2004. Medicare researchers later noted that patients in the trial who took the drugs appeared more likely to die than those who took a placebo, or fake, inert drug.

The drugmakers committed to doing another study, which was supposed to be completed by 2008. It still isn’t finished and Amgen doesn’t expect to finish until 2017 – nearly 25 years after the drug was approved for use in cancer patients.

Still another study funded by Amgen involved dialysis patients with a history of heart trouble. It was supposed to study the effect of the drugs in boosting certain blood levels close to normal, instead of simply higher than the anemic levels, which had been medically acceptable. That trial was stopped three years after it began because patients in the “normal” higher-dose group were dying or having heart attacks at a higher rate than those in the lower-dose, lower-level group.

What should have been a clear warning wasn’t: The FDA didn’t limit the recommended dosing levels, and the reason for the “increased mortality” at the higher doses, according to the label, “is unknown.”

In 2006, a study published in the New England Journal of Medicine reported that kidney patients taking higher doses were linked to higher risks of hospitalization, strokes and death. Some Danish researchers stopped a trial of Aranesp in cancer patients because of an increase in deaths and tumor growths.

Finally, the FDA ruled out the drugs’ use for cancer patients considered curable and for patients considered only slightly anemic. Maximum recommended doses were lowered, and the agency told doctors to use the smallest amount possible to avoid a blood transfusion. The agency removed the quality-of-life claims from the label.

Last year, nearly two decades after the Office of the Inspector General first suggested it, economic incentives to use more of the drugs on patients in dialysis were withdrawn. Medicare implemented a system under which health-care providers are allowed a certain amount of money per dialysis patient, rather than more money for each dose.

“The effects were immediate,” The Post reports, “suggesting again that health is not the only factor that doctors weigh in treating patients. After a quarterly sales plunge in April, Amgen chief operating officer and President Robert Bradway blamed the drop on the new payment scheme.”

Still, no major class-action lawsuits have been mounted, presumably at least in part because the patients taking the drugs were already ill. Amgen has been hit with whistleblower lawsuits alleging that the company engaged in illegal sales tactics.

But for people like Sherry Lenox, questions remain: Although her husband’s death certificate says he died of cancer, did he? Or was he he killed by the drugs he took to treat it?

Patrick Malone & Associates, P.C. listed in Best Lawyers Rated by Super Lawyers Patrick A. Malone
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