Back in mid-March, when a paper in the medical journal Circulation raised questions about possible kidney problems associated with Johnson & Johnson's (JNJ ) heart-failure drug Natrecor, the company moved swiftly to defend the potential blockbuster. Execs argued that much of the journal data was based on doses well above those approved and used by doctors. At approved doses, they pointed out, no evidence of increased risk of kidney failure or need for dialysis has emerged. Wall Street was reassured, and J&J's stock actually gained ground in the days after the paper's publication.
But despite J&J's public relations push, the Natrecor controversy is only beginning. Several top cardiologists, including two on the Food & Drug Administration panel that recommended approval of the drug in 2001, are now voicing an even greater concern: A key trial of the drug showed it might be linked to a higher death rate. If those fears prove true, it could limit the potential of a drug that some on Wall Street expected to surpass $1 billion in sales by 2007.
Scios, the J&J unit that developed Natrecor, continues to insist it is safe. And so far, the FDA has not pushed for a new trial to assess the mortality risks, nor has the company completed a study specifically on the issue. But given the recent problems with Vioxx and other drugs, experts say J&J needs to take Natrecor's potential problems more seriously. "We've had data for some time that mortality goes in the wrong direction with this drug," says Dr. Milton Packer, a cardiologist who chaired the FDA panel that recommended the drug's approval. He says the panel made its decision because the drug appeared to ease the labored breathing of patients hospitalized with congestive heart failure. But he says the panel also said the drug warranted further study.
In the key trial done to gain approval, the mortality rate for patients six months after they got the drug was higher than for those who received the older drug nitroglycerin. While the trial wasn't large enough to prove conclusively that there was a higher death rate, it was a sign of a possible problem.
Scios insists complications muddied results from that trial. Dr. Darlene Horton, the company's senior vice-president for clinical research, says the people who got Natrecor were higher risk patients than those getting nitroglycerin due to kidney and other problems. So when you adjust for the differences in health between the two groups, the increased death rate disappears. And while she acknowledges that the issue of a higher mortality rate has not been definitively answered, she says Scios has a large clinical trial program under way that will ultimately answer the question.
Until now, the FDA hasn't been too concerned either. Dr. Robert J. Temple, associate director of medical policy, says the agency didn't require another trial to answer the mortality question for many reasons, one being that the class of drugs including Natrecor, which work by relaxing blood vessels, haven't been linked to big safety problems in the past.
But more and more people are taking the drug -- and some for longer periods than originally intended. While Natrecor was studied for short-term treatment of acute heart-failure symptoms, cardiologists say some doctors are giving it to patients over several weeks in the hope that it cuts down on rehospitalizations and deaths. And while Scios is conducting studies looking at longer-term use, for now there's limited data on the potential risks or benefits.
If successful, those trials could open up a big new market. No doubt J&J, which paid $2.4 billion for Scios in 2003 in part due to the promise of Natrecor, is putting big bucks behind exploring all the potential benefits of the drug. But the pressure is building to provide answers to nagging questions about risks.
By Amy Barrett in Philadelphia with John Carey in Washington