West Coast Editor

"Racial profiling" is a phrase almost guaranteed to incite controversy in most contexts, and maybe that's why the words are seldom heard in talks about NitroMed Inc.'s BiDil, a heart-failure drug designed specifically to target African-Americans, who suffer the condition about twice as often as whites.

At least, not lately.

When scientists several years ago discovered that the compound - which combines the generic drugs isosorbide dinitrate and hydralazine - worked better in that population than others, the decision about whether to go ahead with BiDil's development seemed a matter of black and white.

And last month, when Lexington, Mass.-based NitroMed halted a confirmatory trial with BiDil based on early positive results, the company's shares skyrocketed more than 73 percent, validating the drug, the approach and the people who had championed BiDil from the start. (See BioWorld Today, July 20, 2004.)

It has not always been so. In 2001, an article in the New York Times headlined "Skin Deep: Shouldn't a Pill Be Colorblind?" noted that "the NitroMed study comes as the federal government is spending millions to research and eliminate racial disparities in health, a goal that reinforces the idea that, in medicine, race is important. But it isn't, say a growing number of scientists, who have concluded that race is purely a social convention, with no biological significance."

Another pair of editorials appeared several years ago in the New England Journal of Medicine, one of which bore the headline: "Racial Profiling in Medicine," recalled Anne Taylor, head of the steering committee for the BiDil trial and professor at the University of Minnesota School of Medicine. She called the headline "horrible" and the editorial itself "scurrilous," adding that the noise since has died down somewhat.

"The issue hasn't gone away completely, but it's kind of quiet now," she told BioWorld Today. "I think the troops are reconvening, trying to figure out where to yell and scream about this [next]."

Biology long has recognized population-specific genetic markers, and certain genetic illnesses are known to be more common in particular groups, such as the lysosomal storage disorder (LSD) Tay-Sachs in Ashkenazi Jews, primarily due to the lack of genetic heterogeneity. LSDs "usually are single-gene diseases, and heart failure is not," Taylor noted.

"What we've done is identify a mechanism not used in previous therapy," she said. The task now is to discover what factor or factors allow BiDil to work, "whether it's genetic, metabolic, by risk profile" or some other way, she added.

"It's a very rich database," Taylor said of the data from the study. "Thought was given at the beginning of the trial to identify predictors of response that transcend ethnicity."

Anyway, prevalence of heart failure in blacks is relative, she said.

"I don't believe for one minute there are people of other ethnicity who will not benefit [from BiDil]," she said. "Heart failure's a terrible disease. I don't think any physician treating advanced heart failure is going to say, Black folks' medicine, can't use it, I'm going to let my white patients die.'"

Generics Could Threaten Politically Correct' Drug

Analyst Chao said BiDil's prospects might be more threatened by something other than pundits on the op-ed pages.

"The concern over generic threat is not a new one for this sort of agent," she told BioWorld Today. "Could generics try to fuel use of these separate components [in the pill] by using NitroMed's visibility? They could." But physicians would have to write two prescriptions, and patients would need to take two pills instead of one.

In terms of expected pricing, "we're talking about the difference of a dollar to $1.50 per day," with the extra cost matched by BiDil's convenience, she said.

"People who are aggressively negative can find vulnerability" in the stock, Chao said. "They can run to the unknown, which is intellectual property."

NitroMed has two issued method-of-use patents, one of which covers isosorbide dinitrate combined with hydralazine to treat heart failure in African-Americans. Known as 463, it expires in 2020. The other, known as 179, covers the combo drug when used to reduce mortality associated with chronic congestive heart failure, and expires in 2007, although the Hatch-Waxman Act could provide protection for the 179 patent through the first half of 2008 - by which time BiDil could be well established.

The 463 patent is another matter, since it narrows the BiDil claims (to African-Americans) rather than broadens them, as is customary in successive patents. Chao called the precedents for securing protection under 463 "less clear," but also said the strong results with BiDil mean its use might eventually extend beyond the African-American subset and even "offstream into less-severe heart failure patients."

Chao forecast BiDil revenue of $122 million in 2005, $190 million in 2006, $269 million in 2007 and $347 million in 2008. When the data are analyzed and disclosed at the American Heart Association meeting in November, something of a reversal in attitude might come about.

"I would anticipate that it would be politically incorrect not to acknowledge the validity of this survival benefit," she said.

NitroMed's stock (NASDAQ:NTMD) rose 35 cents Friday to close at $18.45. n