Monday, August 12, 2013

The BiDil Scam

Of all the facts and figures in Dorothy Roberts’ book, Fatal Invention: How Science, Politics, and Big Business Re-create Race in the Twenty-First Century (New Press: 2011), the BiDil scam best gives the flavor of how this re-creation of race is being done. Targeting a serious health problem among African Americans—heart failure—the BiDil ‘inventors’ promoted a type of pill said to be specific for blacks. They thus not only tried to make a fortune on the misfortune of a downtrodden group, but also reinforced the idea that major illnesses are genetic—due to defective genes—rather than based in social and cultural deprivation. As Roberts argues tirelessly throughout the book, the current focus on genetic difference is just a new and more insidious way of establishing that racial differences, the concept of race itself, are real and biological rather than the product of societies that wish to justify their exploitation of some groups as biologically inferior.

Heart failure affects millions of Americans each year when the heart muscle, weakened by a heart attack, high blood pressure or infection, no longer pumps a sufficient supply of blood. Patients become weak, short of breath, and most die within five years of diagnosis. A cardiologist named Jay Cohn around 1970 hypothesized that vasodilators—drugs that relax blood vessels—might help as a treatment. The prevailing vasodilator, sodium nitroprusside, had to be administered by injection. Cohn came up with the idea of combining two generic vasodilators, Hydralazine and Isosorbide nitrate, into a single pill that could be taken orally. By helping the body make more nitrous oxide, the vasodilator combination would widen arteries and let more blood flow through. The key, though, is that no new drug was involved here. Cohn simply combined two already-available generics into a single pill, and patented them as a new drug for a new purpose. When he and other cardiologists ran a trial on 642 black and white patients, they found that the combination pill did lower the death rate. This was great news for Cohn initially. But then a new trial was conducted, this time comparing the effectiveness of the H-I combined pill with an “angiotensin-converting enzyme (ACE) inhibitor called enalapril.”  The study found that enalapril was even more effective than H-I at lowering the death rate, and these ACE inhibitors subsequently became the preferred treatment for heart failure.

Cohn at this point had no useful drug to peddle, but he wasn’t discouraged; after all, the era of making millions on a patented drug was in full swing. So Cohn filed a patent in 1989 for his combined H-I pill, not mentioning race, and then became partners with a biotech firm, Medco, to whom he licensed the property rights. In 1996, Medco applied to the FDA for a New Drug Application for the drug it christened BiDil, also never mentioning its efficacy or lack thereof for any particular race. Long story short, the FDA refused to approve the new drug, finding that the case for BiDil was not convincing. At this point, Medco gave up and returned the rights to Cohn, who was now in a bind. He had only 10 years left on his patent and he needed something to give it new life. Then he had another eureka moment: he decided to patent BiDil—which he had previously patented without regard to race—as a therapy specifically for African Americans. He and one of his researchers named Carson returned to the original data, broke down the statistics by race, and published the new results in the Journal of Cardiac Failure claiming that, based on their retrospective analysis of the original trial, “the H-I combination appears to be particularly effective in prolonging survival in black patients.” They also claimed that enalapril worked especially well with whites, and concluded that “therapy for heart failure might appropriately be racially tailored” (Roberts, p. 170).

Despite the clear problems with the small size of the test sample and the real possibility that other factors might have contributed to the different outcomes for whites and blacks, Cohn kept pushing, and in 1999 relicensed his intellectual property rights to yet another pharmaceutical company called NitroMed. The new patent submitted by Cohn and Carson stated that “the present invention provides methods for treating and preventing mortality associated with heart failure in an African American patient.” One of the great benefits of the new patent was that where his original patent was due to expire in 2007, the new one gave Cohn another 13 years, till 2020, of control over his drug. This was not because he had invented a new drug, but rather had reinvented “an existing therapy as race-specific.”

Cohn and NitroMed then went to the FDA to get approval for BiDil as a drug specifically for African Americans. The FDA said that if the applicants could prove in a specific trial that the drug worked specifically for African American patients, they might approve it. NitroMed and its CEO, Michael Loberg set out to raise the money for a drug trial, promising millions in revenues the very first year blacks started using the pill. Rather quickly, $34 million in financing showed up, with investors and even banks salivating at the prospect of such a bonanza. Thus, the African American Heart Failure Trial (A-HeFT) began in 2001. The trial included about 1000 African American men only (no whites or other groups) supplied mainly by the Association of Black Cardiologists, who were enthusiastic. Half the subjects received BiDil in addition to standard heart failure medicine, while half got only the standard therapies. The results were so positive for BiDil that the trial was stopped ahead of schedule; BiDil increased survival by as much as 43 percent. Loberg and NitroMed were ecstatic, releasing a report claiming that 750,000 diagnosed African Americans with heart failure (900,000 expected by decade’s end) would be using the drug for a projected income of nearly $1 billion.

BiDil’s chances were improved for FDA approval by the lobbying of many African American groups who saw the chance to finally have therapies, equal to white therapies, designed for black Americans. Even the Congressional Black Caucus urged approval. But the FDA was concerned about the lack of any real scientific evidence to support the claim that the drug worked specifically for blacks. Nor was there any control group of white or other groups for comparison to back up the claim. The FDA also said there was little precedent for designating a drug for any particular racial group: drugs tested on mostly whites were not designated “white drugs.” But with the chair of the FDA approval committee arguing in its favor, the FDA finally approved NitroMed’s application for BiDil, even without scientific much less genetic proof about why it worked for blacks. They were satisfied by the claim that there is an unknown physiological mechanism that explains how BiDil works, and race, blackness (specifically blacks self-identifying as African American), was perhaps a proxy or signal for that unknown factor—probably genes. Cohn and Carson in their patent application speculated along these lines, writing that “blacks, particularly with a hypertensive history, may have a greater deficiency of nitric oxide generation that is restored” (177) by their drug. In 2005, the FDA even claimed that its approval of BiDil was an important step towards the long-desired “promise of personalized medicine.”

In the end, however, even with FDA approval, BiDil failed; so did NitroMed, and so did Jay Cohn’s dream of making a fortune. Roberts says this by way of an initial explanation:

NitroMed did not make money from a drug that was developed to treat heart failure in black patients. It made money by converting a drug for heart failure into a drug for African Americans based on unsubstantiated claims about racial difference. (p. 185)
Here is how it broke down: even with the encouragement of the NAACP and the African American Cardiologist’s Association, only a mere 1% of those 750,000 black heart-failure patients bought prescriptions for BiDil. Part of it had to do with the price. BiDil pills were priced at $1.80 per pill, with a recommended dose of 6 pills daily. That would be $10.80 per day, or nearly $4,000 per year. That adds up to 4 to 7 times the price for the generic drugs of which it is made, so the insurance companies refused to pay the approximately $3,000 extra per year for BiDil compared to the identical two generics. So did Medicare part D and Medicaid. And they were right. BiDil was not a new drug; it was just a clever combination of two drugs already available in generic form! It was a drug that had not originally been targeted to black people or white people or any specific group. Only when the original FDA application failed did the ‘clever’ cardiologist named Jay Cohn come up with a new ploy: market it specifically to black people; and then show how it works; and then massage the marketing to appeal to the sense among African Americans that no one cares about their specific health problems; and Eureka, you’re a billionaire.

            Fortunately, BiDil and NitroMed crashed and burned. People of color were not so dumb after all; rather, they were suspicious from the get go. But it makes one wonder: how many other “miracle” drugs have been hatched and marketed the same way? In a pill-crazy culture like the United States, one would have to guess “a lot” (just think of all the statins taken by Americans desperate to reduce their cholesterol).  Sadly, though, the underlying problem exhaustively chronicled by Roberts is sure to recur. Race-based pharmaceuticals—what have been called pharmacogenics or pharmacoethnicity—are sure to return again and again. It’s as old as snake oil: there’s gold in them thar hills. And cardiologists—I know, having consulted them for some time now—and pharmaceutical companies are among the nation’s most avid and mercenary prospectors.

Lawrence DiStasi

No comments: