BALTIMORE -- A Medicare advisory committee has voted that there is not enough evidence to warrant off-label use of recombinant human bone morphogenetic protein, or BMP, for bone surgery.
The bone growth agent is increasingly being used as a substitute for iliac crest bone graft during spinal fusion and tibial fractures.
Currently, two recombinant BMPs -- BMP-2 and BMP-7 -- have some form of FDA approval and are commercially available in the U.S. There are only six uses explicitly approved by the FDA.
But, in an analysis presented at Wednesday's meeting of the Medicare Evidence Development and Coverage Advisory Committee (MEDCAC), a Blue Cross Blue Shield Association researcher estimated that up to 73% of all procedures using BMP are for off-label uses.
Other estimates place that figure closer to 85%.
Although many off-label uses are considered safe, notable concerns have surfaced recently, including formation of bone in unwanted locations and the potential for the protein to fuel the growth of cancer cells or spark adverse immune system reactions.
The MEDCAC panel voted that there is adequate evidence to support using BMP for FDA-approved uses for lumbar spine fusion and open tibial fractures.
But the panel was not at all confident about endorsing the use of the proteins for another lumbar spine indication for which the FDA granted special humanitarian device exemption. Such exemptions are granted for drugs or devices to treat conditions that affect fewer than 4,000 people, but does not require the company to demonstrate effectiveness.
The panel also expressed extremely low confidence that using BMPs off-label in the cervical spine would produce any clinically meaningful health outcomes, echoing a study published in the Journal of the American Medical Association last year that found that BMP increased complications. (See Spinal Fusion Agent Raises Costs, Complication Rates).
"There is some evidence to support [BMPs] if you confine your use to FDA-approved indications," said panel vice-chairman Saty Satya-Murti, a neurologist in Wichita, Kan. "There is not enough evidence to support off-label use."
Panelists at Thursday's meeting did not address whether or when Medicare should pay for BMPs -- that meeting is likely still a few years off. Rather, Thursday's meeting was more of a message to industry on what questions still must be answered about the protein, Satya-Murti told 鶹ý. Chief among them: What are the long-term effects of using BMPs?
About 90% of all studies on BMPs are funded by industry -- an issue that has raised eyebrows in the past.
When a group of FDA advisers met in January 2002 to consider whether to recommend marketing approval for BMP-2, one of them raised a question about the research findings that Medtronic, the maker of Infuse, filed with the agency as part of its application process.
The advisory panel member pointed out that nine of the doctors who authored the BMP-2 research submitted to the FDA had a financial stake in the product. Moreover, the studies by those nine all had findings that were twice as good as studies from researchers who did not have a financial interest in the product.
Several MEDCAC panelists expressed concern about the dearth of nonindustry funded BMP studies. However, getting those studies would mean the federal government would need to put up some funding for research grants, said Satya-Murti.
The FDA is expected to make a decision soon on whether to grant marketing approval for Medtronic's investigational spine stabilization device Amplify, which uses rhBMP-2. In July an FDA advisory panel split over whether to recommend approval for Amplify, citing lack of data to prove that the benefits outweigh the risks for degenerative disc disease patients.
Although Medtronic's other spine device, Infuse, also uses rhBMP-2, Amplify is the first combination product utilizing rhBMP-2 for posterolateral fusion treatment of degenerative disc disease.