Race-related controversy causes drug flop

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Jay Cohn, a cardiologist for more than 50 years, was fighting a losing battle against heart failure in the 1980s. Treatments of the day weren’t working, and people were dying at a rate of 20 percent per year.

Nearly two decades later, the University of Minnesota Medical School professor was thrilled when BiDil, the drug he called “remarkably lifesaving,” received approval from the U.S. Food and Drug Administration in 2005 to treat heart failure.

But the fanfare was short-lived; the drug flopped.

Much of its financial failure is because of controversy over its approval for use in black patients only.

Some retaliated, saying researchers had no basis to market the drug to a specific race. Cohn disagrees and says confusion surrounding the issue has crippled BiDil’s ability to treat patients who need it.

“The ultimate prejudice is to not treat black people with heart failure with this drug,” he said.

A tale of two compounds

Nitrate and Hydralazine – a combination that would form BiDil – was originally studied in 1980 on a group of 642 male veterans. The 186 patients who received the drug combination showed a slight reduction in mortality compared to those who didn’t.

Several trials later, the researchers brought the combination to the FDA for approval in 1996, but it was rejected due to lack of evidence.

Revisiting the original study, Cohn noted a particular benefit in the black patients compared to white patients, prompting a repeat of the trial in 2001 on only black patients.

The African-American Heart Failure Trial studied the effects of the drug on 1,050 black heart failure patients already on standard therapy regimens.

With a 43 percent reduction in mortality and 39 percent decrease in hospital visits among patients, the study was stopped early and BiDil was approved.

The significant benefit in blacks warrants marketing the drug to them, said study chairwoman Anne Taylor, now vice dean of academic affairs at Columbia University Medical Center.

“However, I don’t think it absolves us of the responsibility to understand what the specific mechanism is,” she said, “and whether that mechanism exists in lesser prevalence in other populations.”

Cohn and Taylor conducted the BiDil trial, with its manufacturer, NitroMed, footing the bill.

The National Institutes of Health is considering mounting a new BiDil study on white patients, Cohn said.

The prevailing hypothesis is that BiDil supplements nitric oxide, a chemical that blacks tend to lack more than other populations, Cohn said.

“That’s the basic mechanism by which the drug acts and the rationale for why it’s more effective in black people,” he said.

But not everyone agrees.

In the past, clinical trials have always used white patients to approve drugs for everyone, Dorothy Roberts, a law professor at Northwestern University, said in a speech at the University of Minnesota in February.

“All of a sudden, a trial involving only African-Americans could only prove it works in blacks,” she said at the lecture. “By approving BiDil for use only on blacks, the FDA emphasized the supposed distinctive – some might say substandard – quality in blacks. The message is black people can’t represent all of humanity the way that white people can.”

What the FDA should have done, she said, is rejected the researcher’s request for race-specific approval and approved the drug for all patients.

‘There’s nothing wrong with different’

The simple fact is that there are distinct physical differences among racial populations that help

doctors characterize their patients, Cohn said.

“To claim that there are no differences is absurdly naïve,” he said.

These differences put blacks at a greater likelihood of hypertension, kidney failure and cardiovascular disease, much of which can be accounted for by their nitric oxide deficiency, Cohn said.

Although race-specific drugs may seem like an effective tool, for some, it could be used as a means of segregation, Selwyn Vickers, professor and chairman of the University Medical School’s surgery department, said.

“As an African-American, you may find that not an asset but a stigma and liability,” he said, “because now a third party insurance company now has a marker that keeps you from getting insurance or that keeps you from getting a job or that keeps you from doing any number of things.”

A few months ago, Vickers received a $4 million NIH grant to develop better minority recruitment strategies for clinical trials.

“Right now, trials reflect those who have access,” he said, “not the majority of our population as it relates to the future.”

Reinforcing a false, biological definition of race in pharmaceuticals would worsen racial inequities, Roberts said.

Taylor likened racial differences to flowers in a garden. When someone plants lilacs and roses, there’s no question of better or worse; rather, it’s a matter of tending to their specific horticultural needs.

Discourse in the United States is poisoned by the assumption that racial difference means one must be better than the other, she said.

“It doesn’t at all; it just means different,” she said, “and there’s nothing wrong with different.”