One of the most controversial drugs ever made could disappear if a new marketing plan can’t save it.
Widely known as the “race-based” medicine, BiDil (isosorbide dinitrate and hydralazine hydrochloride) was launched in July 2005 by Lexington, MA-based NitroMed (NASDAQ: [[ticker:NTMD]]) for treatment of heart failure in black patients. The wording of that approval caused quite a fuss, as people debated the up- and down-sides of prescribing drugs based on skin color.
But despite having lots of free publicity and remarkable clinical trial results, the pill has made a dismal showing. NitroMed did not come close to its original 2006 guidance of $20 million in sales. Instead, it earned a paltry $12 million or so from BiDil last year, and its doing only slightly better now. Things are so bad, NitroMed’s stock is currently hovering just above the dreaded $1 mark. The company has ditched all R&D, except work on a once-daily version of BiDil, and last year it completely retooled its marketing plan to try and rescue the drug.
Ironically, NitroMed says part of the problem was that BiDil was approved faster than anticipated. Pressed to start marketing before they were fully prepared, management turned to a contract sales force. “That is not ideal,” says Gerald Bruce, senior vice president of commercial operations. NitroMed was also slow to get the drug onto key formularies, making it too expensive for many patients.
Bruce came on in early 2006 to lead the new charge. A pharma veteran who has worked at Bristol Myers Squibb and Johnson & Johnson, Bruce says, “Our focus now is on growth. We will meet our targets and go from there.” There are promising signs. The company has finally gotten the drug onto enough formularies that about 80 percent of patients should have affordable access, per a company press release. Management also dumped the contract sales team for “A small but experienced internal specialty sales force focused on key hospitals and the high-prescribing doctors,” says Bruce.
But will that be enough to save the drug? One odd thing about BiDil’s predicament is that no one has ever disputed that it works. It makes such a huge difference, decreasing the rate of death among heart failure patients’ by about a half, that the Phase III trial (called A-HeFT) was stopped early so all patients could be switched to the new drug.
What riled people about BiDil was that, for one thing, it is a combination of two generic pills. So why can’t doctors just prescribe the two cheap pills instead of BiDil? NitroMed argued that there was an advantage to BiDil, and the company recently served up published clinical data that show that BiDil releases the two drugs into the system at a different rate and concentration. “This shows you can’t just substitute the generic components and get the same effect as the fixed dose combination,” says Welton O’Neal, vice president of Medical Affairs at NitroMed.
Then, there’s the race issue.
Some people charged the company with exploiting a tragic racial health disparity to make quick money. Heart failure is one of the many diseases that kill blacks at a much higher rate than whites. NitroMed was able to speed BiDil to market because its components are already approved, and there was earlier data on the combination’s effects. In fact, a careful review of that data pointed to a new use for the drug: In a mixed race trial, the combination showed no benefits overall. Blacks, however, seemed to do better on the drug.
NitroMed decided to pick up that data and run with it, all the way to FDA, which gave them approval to conduct A-HeFT — the first ever black-only trial for heart failure. The company also rallied many minority organizations, including the Association of Black Cardiologists, which co-sponsored A-HeFT. Within just a few years after that crucial first FDA meeting, BiDil was approved for use in “self-identified” blacks.
Support from minority groups didn’t spare NitroMed the barbs, however. Critics charged that race-based medicine would deepen the racial divide and that the company should have spent the time and money to find a better marker of who would benefit from the drug than self-determined race. “I realize it’s all they have now, but I’m just concerned that skin color is not a good enough measure of who responds,” says Stephen B. Liggett a professor at the University of Maryland, School of Medicine. African Americans are really a diverse population, he argues, and “Race-based medicine is a very tiny step, and one that could give the wrong message.”
Liggett and others are pioneering the use of new genetic markers to more accurately guide prescribing. NitroMed has done a little looking for such markers itself, but the genetics underlying response to the drug are still murky. In fact, it’s not even clear yet exactly why the combination works, let alone who responds best to it.
In the end though, the debate about race is probably not the root of BiDil’s woes. “Those issues are raised at academic conferences, but the medical community is driven by data and what the FDA says,” says Ken Bate, who became NitroMed’s new CEO in early 2007. “That’s not something our sales people confront with any frequency whatsoever.” Among the factors that could be impairing BiDil’s market uptake are side effects. Although the company calls these effects manageable, the drug does cause more headaches and dizziness than traditional therapy.
NitroMed also knows that “BiDil is promotionally sensitive,” says Bruce. If the company gets its message out to doctors, prescriptions should go up, he says, “Because the number-one driver physicians focus on is mortality benefit.”
That message should now be getting to the right people. But if the drug still misses the mark, it’s unlikely NitroMed will get many more chances to rescue it. And marketing muscle alone doesn’t make a product, as Pfizer and Nektar recently learned with their multi-billion dollar bomb Exubera, the inhaled insulin.
Unless NitroMed can snag a partner for the drug, BiDil’s fortunes—and those of NitroMed—will rise or fall along with the trajectory of the next few month’s sales figures. “I expect to see some impact [of the new program] at the end of this quarter,” says Bruce.