FDA Unanimously Approves a New Controversial Heart Drug for African-Americans

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• JEFFREY BROWN:

  The Food & Drug Administration must now decide whether to approve a new drug that raises difficult ethical questions about medicine and race. The drug, known as BiDil, is to be marketed by its manufacturer, Nitromed, as a treatment for African-American patients suffering from heart failure. If approved, it would be the first pill to target a specific racial group.

  BiDil is a combination of two generic drugs. Eight years ago, the FDA withheld approval for use by the general public, deciding at the time that the research did not show a significant benefit. But a more recent study of the drug, focusing only on African-Americans, found that BiDil did make a difference, reducing the death rate among blacks by 43 percent, compared to the use of standard heart medications and a placebo.

  Yesterday, an FDA panel voted unanimously to recommend approval of BiDil. And a majority of the panel agreed with the company that the drug could be labeled as specifically for African-Americans. Vivian Ota Wang served on that panel. She is with the National Human Genome Research Institute. Also with us is Dr. Keith Ferdinand, a member of the Association of Black Cardiologists and a clinical investigator for Nitromed in the recent study of BiDil's effectiveness. Welcome to both of you.

• DR. KEITH FERDINAND:

  How are you doing?

• JEFFREY BROWN:

  Dr. Ferdinand, starting with you let's explain what this drug is. What does it do? Define heart failure for us and who would this help?

• DR. KEITH FERDINAND:

  First of all, heart failure is a very serious condition. Over 700,000 African-Americans have this condition. It has the death rate, or mortality rate, similar to that seen with certain cancers. Once a person has moderate to severe heart failure, the death rate can be as much as 50 percent over three years.

  So if the person has a heart that's dilated, it's not pumping well, what the study we did showed was that if you add a combination of a drug known as isosorbide dinitrate and hydralazine – it would be marketed under the brand name of BiDil – this drug would, added to the conventional medications, cut death rate or mortality rate by 39 – 43 percent and hospitalization by 39 percent. So that's really important cause here you have a disease that can kill, that causes hospitalization, causes quality of life concerns and the medication that helps.

• JEFFREY BROWN:

  When would the drug be given, at what point for a patient?

• DR. KEITH FERDINAND:

  Well, it's added to conventional medicines. So you have the ace inhibiters, the angiotensin receptor blockers, beta blockers, diuretics. This is modern medicine. You add the medicine to the conventional therapy that already has been utilized, and we use the term African-Americans but as you know, one of the controversies is that these were self-identified African-Americans.

  And the reason we did that is because that particular population appeared in earlier studies to respond to isosorbide and hydralazine, which is now going to be marketed as BiDil, seemed to respond in an advantageous way. The larger trial was over a thousand blacks. And that's important because this is a population that has a higher rate of heart failure, it comes on earlier, more hypertension and more death rates from heart failure.

• JEFFREY BROWN:

  Now, having done this study and staying with you, Dr. Ferdinand, why might there be more benefits to black patients than to white patients?

• DR. KEITH FERDINAND:

  Well, the study didn't prove that. The older study's concerned that there may be a little bit better of an effect in blacks versus whites. But this study identified an effect only in blacks. So then the question becomes: What should the labeling be? Should it be a medication that's added to conventional medicine for treating heart failure only in blacks? I don't really think so.

  That may be the label at that the FDA utilizes when it finally makes its recommendations. I think what it should say is the following: This drug has been shown to be beneficial when added to conventional modern therapy in patients who have moderate to severe heart failure and it was based on a study of 1,050 self-identified African-Americans — period.

• JEFFREY BROWN:

  That's as far as you want to go in saying that it would benefit more to black patients than to white patients?

• DR. KEITH FERDINAND:

  We don't know what it's based on. There's no genetic marker that says who's black, who's white. And I'm sure Dr. Ota Wang is going to tell you that most people are all the same. The human genome says that we're 99 percent the same and we all come from, what, 10,000 people in East Africa? So it's really difficult to say that there's a marker that says a person who's self-identified as an African-American will respond to a drug versus another person.

• JEFFREY BROWN:

  All right. Well, you've put on the table some of the key questions here. Now, Dr. Ota Wang, you voted in favor of approving the drug, but you were in the minority on the panel that said it should not be labeled specifically for African-Americans, correct?

• VIVIAN OTA WANG:

  Correct.

• JEFFREY BROWN:

  Why?

• VIVIAN OTA WANG:

  For — part of the reasoning is that I don't really — I was not convinced by the scientific evidence that actually it was effective for this broad range of a very, variable group called African-American. I think that the whole issue of — this brings up the whole issue of: Is race biological?

  And I am from the persuasion that it is at this point not biological, that, in fact, the self-identification of racial identity is a complex sort of process that includes social, cultural, and psychological issues and that it really serves as a biological proxy in this particular study.

• JEFFREY BROWN:

  And, of course, there's a lot of disturbing history that comes with seeing race that — in that way.

• VIVIAN OTA WANG:

  Right. And one of the issues that came up in the panel yesterday is the variable nature and subjective nature of being self-identified. And I think it really comes to the issue of the scientific community's comfort level of the — of people identifying themselves racially and that being biologically meaningful.

• JEFFREY BROWN:

  And yet, the tests did, of course, show that it had a benefit for black patients. Is that not important?

• VIVIAN OTA WANG:

  That is exactly one of the reasons why I did vote for approval for the drug. But I am — I'm more hesitant to do the specific labeling mainly because I think it gives us a false sense of biological validity on — that its effectiveness is on a particular group of people who self-identified as black when, in fact, it's such a broad range of people.

  And that, in fact, what we should be looking at are some of the underlying processes related to heart failure. For example, maybe the people who responded better were actually — their heart failure was due to hypertension versus coronary artery disease, and that we shouldn't globally generalize it for all people.

• JEFFREY BROWN:

  You both use the term "self-identify." Explain what you mean by that.

• VIVIAN OTA WANG:

  I think that it's the difference between who I think I am versus who you think I should be. So the example I gave yesterday on the panel is I challenged the people saying if I were to come in to the trial and say I were African-American, would they accept me?

• JEFFREY BROWN:

  Dr. Ferdinand, how do you see the questions raised by having a drug specifically labeled for African-Americans?

• DR. KEITH FERDINAND:

  Actually, we agree more than you would think. We studied African-Americans because if you look at heart failure drugs — and this actually goes for a wide range of medicines, including the cholesterol medicines, which we know are life saving — the percentage of blacks or African-Americans in many of those studies is very, very low.

  Some studies with thousands of patients may have five, ten, or a hundred blacks. And we generalized those responses across all the demographics. So what we wanted to do was to make sure that in this very high-risk patient who has had a signal in the past that they may respond to BiDil that, indeed, there is a response. So we took 1,050 African-Americans, conventional medicines, modern medicines, and then added either placebo in one arm or BiDil in another arm and sit back and see what happens.

  And what happens was there was a decrease in mortality, a decrease in hospitalization and an improvement of quality of life. Self-identified African-American status, some people think, may be a proxy for some genetic marker. I'm not willing to go that far. We really don't know; there may be a physiological answer that's not necessarily genetic.

  For instance, if a person has long-standing hypertension, they may damage their vasculature such that isosorbide dinitrate, which gives a substance called nitric oxide, vasal dilates and preserves the vasculature and hydralazine, which is also a vasal dilator, works as an antioxidant and allows the isosorbide dinitrate to work better. So the physiology may be related to blood pressure, socioeconomic status, stress, socioeconomic disadvantages. We don't know what it is.

• JEFFREY BROWN:

  All kinds of things, which are not biological.

• DR. KEITH FERDINAND:

  In New Orleans where I'm from we call it a gumbo. It could be a mixture of things that causes the response to BiDil.

• JEFFREY BROWN:

  Dr. Ota Wang, if the drug is approved, doctors could give it to anyone, could they not?

• VIVIAN OTA WANG:

  Right. But I think — I agree that I think the labeling becomes important because I'm also very respectful of the time limitations clinicians have in the clinic. And it's much easier to sort of read the label and not sort of think much more broadly of the consequences of such a label.

• DR. KEITH FERDINAND:

  Dr. Ota Wang, let me tell you what I would do. I have a large number of patients of all various racial backgrounds. If I saw a person who self-identified as black, I would treat that person with the best medicine available. If I saw someone who self-identified as Asian, Hispanic or white, I would do the same.

  So although the labeling may be restricted, most good clinicians know that you have to sit down and treat that patient one-on-one. You have to do the best you can for that particular patient.

• JEFFREY BROWN:

  Do you see us, Dr. Ota Wang, moving towards this kind of question more and more as we get more precise information about our makeup?

• VIVIAN OTA WANG:

  I think that in the public it's been raised a lot.

• JEFFREY BROWN:

  This kind of targeted medicine?

• VIVIAN OTA WANG:

  Targeted medicine. But I think that what we have to distinguish is when we talk about targeted medicine, to really target the biological processes of the disease, rather than looking at social proxies that may categorize people that may not correlate very directly with the disease process.

• JEFFREY BROWN:

  All right. Vivian Ota Wang and Keith Ferdinand, thank you both very much.

• DR. KEITH FERDINAND:

  Thank you.

• VIVIAN OTA WANG:

  Thank you.