“Because You Want More Life to Live:” BiDil, a Heart Failure Prescription for “Self-Identified Blacks”

In June 2005, the US Food and Drug Administration made history by approving the patented pharmaceutical BiDil to treat African American patients suffering from congestive heart failure. BiDil, whose generic name is isosorbide dinitrate/hydralazine hydrochloride, is not the first race-specific pharmaceutical (that distinction may belong to Travatan, a brand of eye drops marketed to black patients1) — but it is the first race-specific pharmaceutical to be awarded federal approval.

Its appearance sparked controversy in the medical and bioethics communities, as some lauded the drug’s development and others deemed it a designer drug that sanctioned racial profiling in medicine2 and loaned credibility to the concept of race as biology. This flurry of excitement was matched in the market: anticipation of the drug’s release caused the value of shares in NitroMed, the company that owned the patent to BiDil, to more than triple in the months leading up to the FDA’s announcement.

Citing the medical establishment’s historic neglect of African American patients, NitroMed has promoted BiDil as a bold step by the pharmaceutical industry and a path-breaking effort to reverse long-standing racial health disparities in heart failure. The drug’s development was also hailed by the NAACP and the Association of Black Cardiologists. But in an article written forScientific American, Jonathan Kahn, expert on race and bioethics, lambasted BiDil’s passage to market as a tangled tale of inconclusive studies, regulatory hurdles and commercial motives.3 Kahn pointed out that BiDil is not a new drug, nor was it initially designed for use in black patients. It is a combination of two generic vasodilators, hydralazine and isosorbide dinitrate (ISDN), which increase the bioavailability of nitric oxide, relax blood vessels, and relieve stress on the pumping heart. H/I was patented as BiDil after a series of pharmaceutical trials appeared to confirm its worth as an improved therapy to treat congestive heart failure in self-identified black patients. This claim rests on three assumptions, each to be examined here. First, the claim asserts that the drug is more effective in black patients than in other patients; second, it posits that heart failure is overrepresented among black patients; and finally, it assumes that black is a meaningful category in medicine. The critique of Bidil challenges these assumptions and argues that they promote structural inequalities in health care and misrepresent sociological determinants as biological facts.

1. Shown to Save the Lives of Black Heart Failure Patients

BiDil’s designation as a race-specific drug results from an attempt to justify the patenting of generic drugs, and in order for this to be accomplished, its innovator was required to manipulate the research design of the pharmaceutical trials that appeared to prove H/I’s efficacy in only certain patients. Jay Cohn, a University of Minnesota cardiologist who began using hydralazine and ISDN in combination to treat heart failure, was unable to secure a patent on the two generics, and also failed in an early attempt to secure FDA approval of the H/I combination. Retrospectively reviewing data from earlier trials, Cohn sought to prove that a sub-population had shown strong response to treatment. Leveraging the results of a prior trial which had enrolled just 49 African Americans, Cohn applied for a patent on the use of H/I to treat heart failure in black patients. Approved in 2000, the patent will last until 2020.3

Subsequently, Cohn organized the African American Heart Failure Trial (A-HeFT) in 2004 with a study population of 1,080self-identified black heart failure patients4 at 150 different study sites, including Morehouse Medical School and other historically black institutions.5 The study’s early results were remarkable: the active arm of the study experienced a 43% reduction in mortality, and the data and safety monitoring board of the study determined that it would be unethical to deny the drug to participants who were receiving only standard contemporary modern care. The trial was halted at the 8-month mark to provide H/I to all participants.5

At the conclusion of the African-American Heart Failure Trial, the investigators filed a new application for the therapy’s approval with the FDA. In just months, the FDA decided to approve BiDil, satisfied the drug had been shown to decrease mortality, to reduce hospitalization, and to improve patients’ functional status, and to slow the progression of heart failure in self-identified blacks.5 But because the A-HeFT included only self-identified black patients, it could not confirm whether BiDil is more effective in black patients than in any other population. The frequently cited hypothesis that H/I would yield similar results in patients of other racial groups remains untested.

2. African Americans: At High Risk for Heart Failure?

A fact sheet from NitroMed’s public relations office states that an estimated 750,000 African Americans are currently diagnosed with heart failure, with the number expected to increase to nearly 900,000 by 2010.6 Elsewhere, NitroMed claims that African-American heart failure patients are disproportionately over-represented in the North American heart failure population and that African Americans aged 45-64 face a mortality risk more than twice that of white heart failure patients.7

While these statistics appear to confirm the popularly held belief that African Americans are prone to suffer cardiac conditions more than other racial groups, NYU sociologist Troy Duster argues that NitroMed’s use of these data is misleading. The age group 45 to 64 only accounts for about 6% of heart failure mortality, and for those over 65, the statistical differences between ‘African Americans and Caucasians’ nearly completely disappear.8 This statement is backed up by CDC data showing that heart-failure-related mortality among African Americans has actually declined since 1988, and that this rate of decline outpaces the decreasing level of heart-failure-related death rates in the Caucasian population.9 Apparently, NitroMed is culling data to create the impression that all African Americans are at high risk for heart failure and premature death.

In the Common Questions portion of its website, NitroMed answers the question Why are African Americans at greater risk for heart failure? in two sentences:

Two well-known contributors to the increased risk are much higher rates of high blood pressure and diabetes in the African American community. Other potential risk factors being explored are African Americans’ lower access to and use of health care services, greater exposure to environmental pollutants, and greater tendencies to be overweight and to get less exercise.10

Interestingly, this statement does not mention genetic risk factors, although NitroMed is currently supporting research to isolate gene sequences related to heart failure. However, heart failure is not a genetic disease. As NitroMed correctly states in its own FAQ, the etiology of heart failure is shaped by multiple inputs. As anthropologists W.W. Dressler and colleagues propose, attempts to link hypertension rates in African Americans to single variables (genetic factors, higher rates of obesity and smoking, and socioeconomic status) have failed to explain race-bound health disparities completely.11 And as Troy Duster has argued, the role of racism in the heart health of African Americans may represent the most meaningful link between race and disease prevalence.12 In short, the marketing of BiDil is a misguided – or cynical – attempt to medicalize the stress of racism, and to convert a social problem into profit.

3. Target Markets and Self-Identified Blackness

Finally, the FDA’s approval of BiDil raises a practical problem: How are doctors to determine who is black? Though BiDil’s legally approved patient population consists of self-identified blacks, Bidil.com uses the term African-Americaninterchangeably with black, and company personnel are slippery on the issue of who is eligible for the prescription. In response to a query, a NitroMed representative wrote:

If a multiracial or a dark skinned individual decides that they are a self identified black and a physician believes that BiDil is an appropriate option for their heart failure, then they would be an appropriate candidate for BiDil.13

Self-identified black is a catch-all category that could include patients whose origins are African American, Melanesian, or South African, but the A-HeFT’s study design recognized no distinctions between such populations: a patient might have joined the A-HeFT on the basis of ancestral, regional, genetic, phenotypic, or even cultural blackness. Sidestepping responsibility for racing its participants, the study design of the A-HeFT did not require researchers to confirm that a study participant conformed to any given definition of blackness: though subjects were meant to be screened in on the basis of diagnosis and race, the trial was administered colorblind.14 This point was pressed home at an FDA advisory committee meeting, when a woman of apparent Asian ancestry asked whether she would have been admitted to the study if she’d self-identified as black. The study investigators responded ‘Yes.’14 By refusing to define who may be reasonably considered blackin clinical trials, NitroMed also maximized its market of potential patient-consumers.

Despite early enthusiasm about BiDil, its high public profile, and its strategic efforts to appeal to as many patients as possible, the drug ultimately faced a challenging capital marketing environment. In BiDil’s first year on the market, physicians only wrote 84,000 prescriptions, due partly to insurers’ reluctance to reimburse.14 NitroMed was criticized for the drug’s high cost, which at $1.80 a pill (or $5.40 a day) equaled 4 to 7 times the price of generic isosorbide plus hydralazine. Some physicians prescribed patients to the two generics, despite the difficulty of establishing the correct ratio in a dose.15

In its first year, BiDil turned profits of only $11M, far short of the $100M that analysts anticipated. By January 2008, NitroMed had ceased corporate expenditure for the sales and marketing of BiDil, cut staff from 90 to 20, and retained an investment bank to explore strategic alternatives.16 Roughly translated, NitroMed is for sale.

Though BiDil’s disappointing performance might come as a relief to its critics, its probable disappearance from the market represents a setback for the 5 million Americans who face an incapacitating and potentially fatal disease, and for whom the value of this therapy has barely been realized. The development of race-based therapies or, beyond that threshold,personalized medicine may allow pharmaceutical corporations to create and corner target markets that provide more effective therapies for people with specific conditions, creating an opportunity for improved health for some and higher profits for drug companies. Though pharmaceutical companies often cite these advantages to justify the development of designer therapies, such endeavors siphon resources from research that will address the needs of the greatest number of patients, produce more expensive drugs that may not be affordable to those most in need, and encourage the confusion of sociological factors with biological facts. BiDil’s short-lived moment on the market illustrates the perils of leaving decisions about drug development in the hands of corporate managers whose bottom line is their balance sheet, not public health.

 

Martha Lincoln is a doctoral student in the PhD Program in Anthropology ay the CUNY Graduate Center, New York, New York.

 

References

1. Rose N. 2006. The Politics of Life Itself: Biomedicine, Power, and Subjectivity in the Twenty-First Century. Princeton, New Jersey: Princeton University Press. 2006, p. 181.
2. Schwartz R.S. Racial Profiling in Medical Research. New England Journal of Medicine 2001; 344:1392-1393. 
3. Kahn J. Race in a Bottle. Scientific American. 2007; 297(2): 40-45. 
4. A-HeFT. 2007. A-HeFT.org: The Web site of the African American Heart Failure Trial (A-HeFT.) Available at: http://www.aheft.org/. Retrieved October 30, 2007.
5. Kramer J, Vice President of Corporate Communications, NitroMed, personal communication, October 6, 2007.
6. . Heart Failure Backgrounder. Available at: http://www.nitromed.com/pdf/Heart%20Failure%20backgrounder.pdf, retrieved October 8, 2007.
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10. NitroMed. 2007. Common Questions. Available at: http://www.bidil.com/pnt/questions.php#18, retrieved December 13, 2007.
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12. Dreifus C. 2005. A Sociologist Confronts ‘The Messy Stuff.’ New York Times, October 18. 2005. Available at :http://www.nytimes.com/2005/10/18/science/18conv.html 
13. Neil J. (BiDil Product Manager, personal email, 11/28/2007)
14. Kreimer S. 2007. BiDil not Widely Prescribed. DOC News 4(7): 23. 
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16. NitroMed Reports on BiDil XR(TM) Progress Following FDA Meeting, Announces Restructuring and Suspension of BiDil(R) Sales Force, and Retains Investment Bank to Advise on Strategic Options. 2008. Available at: http://phx.corporate-ir.net/phoenix.zhtml?c= 130535&p=irol-newsArticle&ID=1096799&highlight= retrieved January 21, 2008.