The FDA May Tighten Rules on Omniscan, a GE MRI Drug

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In the past, the agency has tended to follow recommendations from the panel, comprising outside doctors and scientists.

Bayer, in its filing, said the NSF risk for Magnevist is lower than that of Omniscan and Optimark. Mallinckrodt, Optimark's manufacturer, told the FDA that it was revising package labeling to contraindicate, or recommend against, use of Optimark in patients with the most serious kidney impairment. European regulators already have contraindicated use of Omniscan, Magnevist, and Optimark for patients in that class.

In 2007, two FDA medical reviewers independently recommended that Omniscan be contraindicated, as first disclosed in the October story by BusinessWeek and ProPublica. But their boss, R. Dwaine Rieves, rejected the findings. He said that his 2007 decision to treat all the drugs as equally risky was based in significant part on "a very limited database."

an Omniscan "signal for NSF?"

Rieves, who heads the FDA division that oversees imaging drugs, again will help to decide whether the agency should take action based on the panel's input and the agency's new assessment, which relied on a deeper statistical study and additional marketing data.

The review ranks Omniscan highest, by far, on a ratio indicating whether a drug has a "signal for NSF." It also rates Omniscan as the least chemically stable agent, just ahead of Optimark, based on a formula "consistent with real-life conditions." Two weeks ago, European regulators reported a similar finding on chemical stability in a study.

GE says in its latest FDA filing that theories relying on chemical stability "as explanations for the development of NSF are incomplete and flawed." The company also said the relatively high number of NSF cases linked to Omniscan might reflect reporting bias.

The FDA cited 382 cases in which Omniscan was named as the single imaging agent in an NSF report. Magnevist was named in 195 reports and Optimark in 35.

NSF: a mystery in need of research

The FDA put Omniscan's market share from 2005 through 2007 at only 32%, compared with 49% for Magnevist and 10% for Optimark. In the first half of this year, Omniscan's market share had fallen to 17%, the agency said.

Scientists say NSF remains a mystery whose solution could open new insights into related diseases that affect many Americans, such as heart disease. But research into NSF has been slow to gain steam, and the FDA's review singled out GE for tardiness.

The company is the sole drugmaker that has yet to comply with a 2½-year-old FDA mandate that each manufacturer conduct trials on 600 patients with severe kidney disease and on 400 with moderate impairment, a crucial step to solving the mystery of NSF.

"Omniscan has not presented a final protocol for studying" the most severe patients, while all the other drugs are at more advanced stages, the FDA said.

The potential risks of such testing may explain why.

Would Omniscan testing be unethical?

In healthy patients, the kidneys quickly excrete gadolinium agents. So far, the universe of NSF patients consists almost entirely of those with severe kidney disease, which affects a few hundred thousand Americans. A handful of NSF cases are patients with more moderate kidney disease, a condition affecting several million Americans.

Doctors involved with NSF say the FDA's requirement to test patients with severe kidney disease could be problematic, given the known association with Omniscan.

"It would be unethical for any institutional review board or any physician to approve any such study today for Omniscan with that patient population," said Dr. Emanuel Kanal, a University of Pittsburgh professor of radiology who heads the American College of Radiology's blue-ribbon panel on magnetic resonance safety.

GE said that in contacting 684 research centers, none would agree to sponsor a test for a patient with severe kidney disease; only four agreed to trials with moderately impaired patients. With the FDA's approval, the company is looking to conduct the latter trials in Europe and Asia.

Editor's Note: An earlier version of this story incorrectly reported that GE's Omniscan had 58% of the U.S. market for gadolinium-based contrast agents between 2002 and 2007. The company says the 58% figure, which it reported to the U.S. Food and Drug Administration, actually represents the share of Omniscan's worldwide sales inside the U.S.

Gerth is a reporter with ProPublica, a nonprofit journalism organization in New York.