The new drug application claiming treatment of a single, self-identified racial group raised a storm of controversy.
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Isosorbide dinitrate/hydralazine is a fixed dose combination drug treatment specifically approved by the US FDA to be used to treat self-identified black people with congestive heart failure. It is a combination of hydralazine (an antihypertensive) and isosorbide dinitrate (a vasodilator). It is the first race-based prescription drug in the United States.: 7
The combination preparation is marketed in the United States under the trade name BiDil by Arbor Pharmaceuticals, Inc. which purchased the rights to market the drug in December 2011 from NitroMed.
From 1980 to 1985 Dr. Jay Cohn of the University of Minnesota led a clinical trial in collaboration with the US Veterans Administration called the Vasodilator-Heart Failure Trial (V-HeFT I) that tested whether the combination of Isosorbide dinitrate and hydralazine increased survival in patients with heart failure; the results were promising and the study was followed by V-HeFT II, which tested the combination against enalapril. In the meantime, Cohn applied for a patent on the combination treatment, which issued in 1989 as US Patent 4868179. Cohn licensed the patent to a company called Medco, and Medco spent the early 1990s preparing a New Drug Application (NDA) to get the FDA to approve BiDil on the basis of the V-HeFT trials. However, the trials were not designed to support an NDA, and in 1997 the FDA rejected the application because it did not have enough statistical power to show whether the combination really worked.
Cohn re-analyzed the data and found a signal that the drug combination appeared to work better in self-identified African-Americans in the V-HeFT trial, and published a paper on that work, and filed a new patent on the use of BiDil in black patients. It had already been known that African-Americans with congestive heart failure (CHF) respond less effectively to conventional CHF treatments (particularly ACE inhibitors) than caucasians.
The new patent and the old patent were licensed to a company called NitroMed, which ran a clinical called the African-American Heart Failure Trial (A-HeFT), the results of which were published in 2004 in the New England Journal of Medicine. The clinical trial was stopped early because the drug worked so well; it reduced mortality by 43%, reduced hospitalizations by 39%, and improved quality of life markers in African-American patients with CHF.
On the basis of A-HeFT, the FDA approved BiDil in June 2005. In 2006, the Heart Failure Society of America included the use of the fixed dose combination of isosorbide dinitrate/hydralazine as the standard of care in the treatment of heart failure in blacks.: e44
Though BiDil must still be taken three times daily, as must the component pills in separate ISDN-H treatment, the reduction in pill burden has been suggested to improve compliance, and thus a better medical outcome.
The new drug application claiming treatment of a single, self-identified racial group raised a storm of controversy. Some hailed the development of BiDil as a breakthrough for Black Americans (such groups included the congressional Black Caucus, the Association of Black Cardiologists, the National Medical Association, and the National Association for the Advancement of Colored People) and a step to addressing the unique health care needs and health disparities of the African American community.
Others who criticized the preliminary studies argued that the original study did not have a significant number of Black-American subjects to make the BiDil's race specific claims, and that the results of only one clinical trial where Black-Americans were tested does not provide a full and comprehensive study. Furthermore, critics argued that self-identified racial identifications from patients as an indicator for race during the trials were not a sufficient categorization method because these self-identifications were socially constructed and have no biological connection to genomic data.
They argued that the trials represented a new form of scientific racism where race, a socially constructed category, would continue to be present in research as a placeholder for genomic identification.
Additionally, some disagreed with the design of the A-HeFT trial because the trial failed to include any non-African American test subjects. The trial was designed to include only Black American test subjects, therefore failing to show that BiDil has a greater effectiveness in Black Americans than in those of other races.
According to Jay Cohn, the pill's developer, the reason for including only Black American test subjects was the lack of funding for doing a trial in the full population. Meanwhile the patent for the drug was running out and the FDA refused to approve it due to lack of clinical trials, so a loophole was needed to make the sale possible for the company.
- Ferdinand, KC; Elkayam, U; Mancini, D; Ofili, E; Piña, I; Anand, I; Feldman, AM; McNamara, D; Leggett, C (1 July 2014). "Use of isosorbide dinitrate and hydralazine in African-Americans with heart failure 9 years after the African-American Heart Failure Trial". The American Journal of Cardiology. 114 (1): 151–9. doi:10.1016/j.amjcard.2014.04.018. PMID 24846808.
- Whitmarsh, Ian; Jones, David S., eds. (2010). What's the Use of Race?: Modern Governance and the Biology of Difference (PDF). Cambridge (MA): MIT Press. ISBN 978-0-262-51424-8. Archived from the original (PDF) on 5 March 2016. Retrieved 8 December 2013. Lay summary (28 April 2013).
- Jonathan Kahn. BiDil and Racialized Medicine. Chapter 7 in Race and the Genetic Revolution: Science, Myth, and Culture, Eds Sheldon Krimsky and Kathleen Sloan. Columbia University Press. ISBN 978-0-231-52769-9
- Carson P, et al. Racial differences in response to therapy for heart failure: analysis of the vasodilator-heart failure trials. Vasodilator-Heart Failure Trial Study Group J Card Fail. 1999 Sep;5(3):178-87.
- US Patent 6465463
- Exner DV, Dries DL, Domanski MJ, Cohn JN (2001). "Lesser response to angiotensin-converting-enzyme inhibitor therapy in blacks as compared with white patients with left ventricular dysfunction". N Engl J Med. 344 (18): 1351–7. doi:10.1056/NEJM200105033441802. PMID 11333991.
- Taylor AL, Ziesche S, Yancy C, Carson P, D'Agostino R Jr, Ferdinand K, Taylor M, Adams K, Sabolinski M, Worcel M, Cohn JN (2004). "Combination of isosorbide dinitrate and hydralazine in blacks with heart failure". N Engl J Med. 351 (20): 2049–57. doi:10.1056/NEJMoa042934. PMID 15533851.
- FDA approval process page
- FDA approval press release
- Heart Failure Society of America. HFSA 2006 Comprehensive Heart Failure Practice Guideline Archived 2011-07-28 at the Wayback Machine J Card Fail. 2006 Feb;12(1):e1-e122.
- Steve Stiles (13 December 2006), BiDil, regulatory milestone but a tough sell for insurers and patients, charts uncertain course
- Dorothy Roberts. The Color Coded Pill. Chapter 8 in Fatal Invention: How Science, Politics, and Big Business Re-create Race in the Twenty-first Century. The New Press. ISBN 978-1-595-58834-0
- Roberts 2011, p. 171
- Roberts 2011, p. 174
- Roberts 2011, p. 175
- WNYC Radiolab audio story about racial issues surrounding Bidil
- Editors, Scientific American. July 31, 2007 Race-Based Medicine: A Recipe for Controversy
- Scientific American article criticizing approval of Bidil
- Scientific American article response by manufacturer to previous article's criticism
- Response for FDA's Robert Temple to Scientific American article
- Puckrein, G. (2006). BiDil: From Another Vantage Point. Health Affairs . Retrieved October 1, 2013, from http://content.healthaffairs.org/content/25/5/w368.long
- Margaret Kimberly, AlterNet. June 27, 2005 A Bitter Pill for Black Hearts
- Saini, Angela (2019). Superior: The Return of Race Science. Beacon Press. p. 246. ISBN 978-0807076910.