CHICAGO A new analysis showing a link between Medtronic Inc's growth protein used in spine surgery and cancer is likely to hasten the product's sales decline and calls for new scrutiny from health officials, analysts and doctors said.
The study released last Thursday at the annual North American Spine Society meeting in Chicago was a focal point of the gathering.
Since then, surgeons have called for more research on the product, which is already under investigation by lawmakers. Some said the Food and Drug Administration should take another look at the recombinant bone morphogenetic protein-2, or BMP.
Infuse is approved for use in some spinal fusion surgeries, in conjunction with another Medtronic product, to help join, or fuse, discs in the lower back. It is also approved for repair of the shin bone and some dental procedures.
Dr. Eugene Carragee, a Stanford University School of Medicine professor and editor-in-chief of the Spine Journal, analyzed available data and found a stronger-than-expected association between BMPs, which stimulate bone growth, and pancreatic, breast and prostate cancers.
Carragee reviewed pooled data on Medtronic's low-dose Infuse, which has been on the U.S. market since 2002, and its high-dose version Amplify, which the FDA refused to approve last year because of concern over cancer risks.
Surgeons at the meeting said they will sharply curb their use of Infuse, which has been used in hundreds of thousands of patients in the last decade.
Wall Street analysts see sales particularly vulnerable to a crackdown on off-label use, estimated to account for as much as 85 to 90 percent of total use, such as application to other areas of the spine.
Sales of Infuse were about $800 million in fiscal 2011. In August, the company said sales were declining in the high teen percentages after news the U.S. Senate was investigating omissions of safety problems from the drug's clinical trials and the Department of Justice was probing off-label marketing.
Dr. Rick Sasso, a surgeon at the Indiana Spine Group, said he has used Infuse for many years, but will not use the product as often after hearing Carragee's analysis.
"The big concern has been Amplify. This is the first time I heard concern about lower doses ... I think it was the first time for a lot of us," he said. "Until that's cleared up, we'll all have to be very cognizant about what we are doing with BMPs."
Sasso said he would like to see FDA call a panel to review the data, much like the agency did after safety concerns were raised with Merck & Co Inc's Vioxx painkiller. In 2004, Merck notified the FDA it would pull the drug due to its own evidence that it raised the risk of heart attacks.
More recently, doctors raised concern over GlaxoSmithKline Plc's widely used diabetes drug, Avandia. The FDA conducted a further review of the medicine and imposed severe restrictions on its use last year.
Dr. Rocco Calderone, a spine surgeon based in Camarillo, California, said he was concerned about Carragee's findings and will be much more cautious.
"If the patient has a family history (of cancer) or is elderly, I probably won't use it. I'll still use it in selected case," Calderone said. "But more studies are needed. This showed an association, not a direct cause."
Medtronic spokeswoman Marybeth Thorsgaard said the company believes the safety profile reported to the FDA supports the safe use of Infuse for the approved indications.
RESERVED FOR COMPLICATED CASES
Wells Fargo analyst Larry Biegelsen expects surgeons to seek out less expensive biologic alternatives and use Infuse only in the most complicated cases.
"We believe that surgeons are also less willing to use Infuse off-label, which we estimate at about 85 percent of overall use, due to potential lawsuits if a patient has a complication," Biegelsen wrote in a research note on Monday.
"We continue to hear that surgeons are moving away from Infuse, given safety concerns," added Mizuho Securities analyst Mike Matson. "We think cancer concerns could worsen the decline in Medtronic's Infuse sales and could prompt an increase in product liability lawsuits."
Rick Wise, an analyst with Leerink Swann, said that one doctor with a high volume of patients noted that, in the past, "he 'used it all the time -- now I use it four or five times a year.' And he is seeing similar dramatic declines in Infuse use among his peers."
Carragee said he would not like to see Infuse taken off the market because it can help certain patients who have few options. He hopes that, over time, new technology will allow much lower doses of the drug to be used in combination with other growth factors or agents.
"The risk is too high to be used off-label," he said. "I suspect the next step will be a more cautious use of the drug in patients and directing the use to patients at high risk for the bones not healing well."
An FDA spokeswoman said the agency is aware of the cancer issue with the higher dose Amplify and declined to comment further. Medtronic's Thorsgaard said the company has not been contacted by FDA about Carragee's findings.
She said Medtronic has been in ongoing discussions with the FDA since July 2010 when a panel of experts reviewed Amplify.
NASS said it does not have a position statement on the use of BMP, but had asked Carragee to do the cancer risk analysis.
"NASS supports an active, scientific discussion about the published data to identify the roles and limitations of BMP in spine care that optimize patient benefit and reduce risk," said NASS President Dr. Michael Heggeness.
"As a physician and scientist, I must stress that the enormous potential for this powerful molecule in carefully selected situations is undeniable."
(Reporting by Debra Sherman; editing by Michele Gershberg and Andre Grenon)