According to data presented at a national conference of spine surgeons, a bioengineered protein used as part of a surgical procedure could potentially increase patient cancer risks. The spine surgery product known as bone morphogenetic protein-2, or BMP-2, is the bone growth stimulating biological agent used in Medtronic’s Infuse, which has been approved by the FDA, and Amplify, an unapproved product that was the subject of the data presented at the conference. BMP-2 use in spinal surgery has increased, because by stimulating bone growth, it can eliminate the need to harvest a small amount of a patient’s own bone for use in spinal fusion surgery.
The Infuse product was approved by the FDA for its narrow use after an earlier clinical trial showed it worked about as well as a standard hip bone graft in a specific kind of spinal fusion surgery. Once considered a major advance in spine surgery, the Infuse product is now the subject of investigations by the U.S. Senate and the Department of Justice over omissions of safety problems from the clinical trial data. With Amplify, Medtronic was seeking additional FDA-approval for a higher-dose formulation of the BMP-2 spinal fusion product. The FDA refused to grant approval earlier this year, a decision Medtronic is appealing.
Clinical trial results demonstrated a significantly higher number of cancers in the test group when compared to a control group of patients that received bone graft as part of a spinal fusion. An FDA advisory panel last year had narrowly recommended approval of Amplify, but was split over possible cancer risks. In March of this year, the agency notified Medtronic in a “nonapprovable” letter that the FDA would need additional information in order to continue. Based on information provided by Medtronic, the FDA rejected that higher-dose formulation, citing concern about cancer risks. At the national conference, additional findings of the Medtronic-sponsored clinical trial not disclosed in the FDA’s rejection were made public.
The studies indicated that cancer risks were significantly elevated. Three years after surgery, there were 20 cancers in the Amplify group versus five cases in the bone graft group. The accelerated rate of cancer development indicates that BMP-2 may play a role in promoting cancer rather than causing it. The implications for the currently approved Infuse are unknown.
The researchers had information showing that at two and three years after being implanted with the genetically engineered protein, significantly higher numbers of Amplify patients were being diagnosed with cancer. A Journal Sentinel (Milwaukee) investigation revealed that Medtronic and doctors had become aware of information about a ninth cancer case, which pushed the concern to a critical level, at least two months before the paper was published in 2009. Additionally, doctors who received millions of dollars from Medtronic failed to report serious complications with the protein in 13 papers over the span of a decade.
The increasing pressure on the FDA to speed up its approval process for medical devices only exacerbates any future flaws or failings of the approvals system. Industry generally favors a speedier approvals process in order to get products to market, noting that the current process gives advantage to European-based industry. Conversely, the FDA’s changes are being considered when concern for the oversight ability of the FDA about the safety and effectiveness of devices is at a heightened level. The battle between industry and the FDA will certainly intensify as Congress considers legislation governing industry fees paid to the agency.