Federal Inquiry May Hinder Plans to Expand Market for Biliary Stents

A $1.8 billion market for metal tubes used to clear blocked arteries outside the heart may be upended by a US probe into marketing practices by Johnson & Johnson, Boston Scientific Corp., and Abbott Laboratories. 

The FDA said the device makers have already curtailed what the government views as improper sales practices since the Justice Department notified them of the inquiry earlier this summer. The companies are seeking new studies to justify implanting similar stents in veins and arteries, and face a slowdown in sales that have reached $900 million with the unauthorized uses.

While the FDA approved the stents only for clearing bile ducts in liver cancer patients, unsanctioned uses for keeping veins and arteries unclogged increased revenues 10-fold, according to  research published in the American Journal of Therapeutics. At that rate, J&J in June estimated a $1.8 billion market for the stents by 2012, which now seems unlikely, said Frost & Sullivan Inc. analyst Venkat Rajan.

“If they want to expand this market beyond what it has been, then it’s now going to involve new trials,” Rajan, based in San Antonio, said.

Federal Crackdown

The FDA warned device makers about promoting biliary stents for uses other than treating cancer during a March 2007 meeting, said Ann Simoneau, an FDA attorney.

In one case, an unidentified manufacturer’s biliary Web site included a graphic diagram of the circulatory system and no mention of the liver or pancreas, Simoneau said. The agency also asked companies to revise brochures and to stop pitching the stents at meetings for vascular doctors, she said.

“If you’re at a conference where the primary audience is not gastrointestinal or interventional radiologists, which would be the people that you’d expect to use these products, then it gives the impression that you’re trying to reach another audience,” Simoneau said.

The FDA has identified safety risks with unapproved use of biliary stents, agency spokeswoman Karen Riley said.

More than 90% of biliary stent injuries or malfunctions reported to the FDA from 2001 to 2006 involved off- label use, according to an agency study in the July issue of the Journal of Vascular and Interventional Radiology. The number of annual injuries or malfunctions more than tripled during this time frame, to 339 in 2006. A total of 14 deaths from off-label use were reported to the FDA in the six-year period.

FDA Clearance

Applications by the companies to conduct clinical trials for stents to treat so-called peripheral vascular disease are up since the meeting, and companies seem to have cleaned up their marketing, Simoneau said. Peripheral vascular disease affects about 125 million people worldwide.

The New Brunswick, NJ-based J&J promotes its products “only for the FDA-cleared indications,” said spokeswoman Carol Goodrich.  Representatives for Natick, MA-based Boston Scientific and Abbott Park, IL-based Abbott declined to discuss the investigation or their marketing practices. The three companies do not break out individual sales for the devices.

While doctors can employ a drug or device approved by the FDA for any purpose, so-called off-label use can’t be legally promoted by companies. The US Attorney’s Office also declined to comment. J&J, Boston Scientific and Abbott announced the investigation in regulatory filings in July and August.

Off-Label Use

“The majority of use for the stents is off-label,” said Jan David Wald,  an analyst who covers the device makers for Stanford Group Co. in Boston, MA. If there is a federal crackdown on how the stents can be promoted, the market may hold at about $900 million, or about half J&J’s June estimate, he said.

The non-sanctioned use “isn’t built into the forecast” of any of the companies’ performance, Wald said. “What we’d be looking for is some kind of a decision or an event where it’s a high probability” of new restrictions or guidelines, such as regulators convening an advisory panel on the issue, he said.

Approved Without Trials

Biliary stents, used to clear bile ducts blocked by tumors that cause pain and discomfort in terminal cases, were approved without human trials for humanitarian reasons, said William Maisel, a Harvard University cardiologist who consults on stents for the FDA.

Stents implanted in locations away from the heart help prevent the body from forming clots that can spur heart attacks and strokes. For such a use, the FDA traditionally requires trials that can take two to three years to conduct, add “tens of millions” of dollars to the cost of product development and risk failure, Maisel said.

No one doubts terminal cancer patients deserve quick access to new medical technology, he said. “The problem is the industry recognized and appreciated this was a backdoor to get some other devices approved.”

Companies have contacted the FDA to discuss clinical trials for new stents to treat peripheral artery disease, said agency spokeswoman Riley. For competitive reasons, the agency doesn’t disclose if companies have applied to hold trials or if they have sought device approvals.

J&J hasn’t sought or received approval for new biliary stents or trials in the past year, spokeswoman Goodrich said in an e-mail. The company has finished enrolling patients in a previously approved study of a stent for treating obstructive superficial femoral artery disease, she said.

Three Studies

Abbott is working on three studies of stents for peripheral artery disease, said spokesman Jonathon Hamilton. Paul Donovan,  a spokesman for Boston Scientific, declined to comment.

Doctors have implanted 1 million biliary stents for unsanctioned uses over the last four years, 90% of all implants during that time, according to Maisel’s study published in the American Journal of Therapeutics in January.

Physicians have used biliary stents for peripheral vascular disease for more than a decade, said Frank Pomposelli, a surgeon at Beth Israel Deaconess Medical Center in Boston, MA. Veins and arteries in the legs and elsewhere are larger than ones around the heart, requiring larger devices.

While company sales representatives are careful to state the product is approved only for use in the bile duct, they “let you know they’re being used” elsewhere too, Pomposelli said.

Biliary stents, which are larger than similar devices made to be used near the heart, have “revolutionized the treatment of peripheral vascular disease,” he said. “They’ve allowed us to get away from surgery, which allows less pain, less recovery time.”

SOURCE: Bloomberg.com