July 28, 2010 — The Orthopedic and Rehabilitation Devices Panel of the US Food and Drug Administration's (FDA's) Medical Devices Advisory Committee has voted to endorse approval of Medtronic's novel spine stabilizing device, provided the company performs the appropriate follow-up studies to monitor for cancer, birth defects, and other adverse events.
The panel voted 9 to 4, with 1 abstention, in favor of the safety and 10 to 3, with 1 abstention, in favor of the effectiveness of the Amplify recombinant human bone morphogenetic protein 2 (rhBMP2) matrix device for spinal fusion in patients with degenerative disk disease.
The panel was more evenly split when it weighed the risks and benefits of the new device, which uses recombinant bone morphogenetic protein 2 to promote the formation of new bone. Six panel members voted yes when asked if the device worked well enough to outweigh the risks, but 5 voted no and 3 abstained.
Panel members spent a great deal of time discussing the increased cancer risk seen with the device. In studies presented by Medtronic to the FDA, cancer rates were 3.8% at 2 years and 5% at 5 years in patients receiving the device compared with 0.9% at 2 years and 1.8% at 5 years in patients receiving the standard hip bone graft spinal fusion procedure.
Most of the panel, including cancer experts, was not particularly bothered by this increase. The consensus was that the increase was not statistically significant and could simply be because many patients getting the experimental device were Medicare beneficiaries, a population known for its increased incidence of cancer.
"Is it a meaningful excess? I don't think it is. It doesn't hit me in the face," said Alfred Neuget, MD, PhD, from Columbia University Medical Center in New York City. "There are no cancer clusters. There were 3 cases of pancreatic cancer in the Amplify group, but this was in Medicare patients aged 67, 76, and 77. If these cases were in people in their 40s, they would stand out like a sore thumb, but using the Medicare group to see a marginal gain in cancer is going to be difficult.
"I see clusters all the time, so I'd say don't worry about it," he said.
But Carmen Allegra, MD, another cancer specialist on the panel, from University of Florida, Gainesville, admitted he was concerned about a potential for cancer. "We are putting patients on a growth factor and might stimulate the growth of a latent cancer. I think we need to follow this further, and I'm not sure a Medicare database is the right place to look. At any rate, we need more information."
William Rohr, MD, a physician with a private practice in Fort Bragg, California, told the FDA that the reservations he had about the cancer issue were put to rest by the cancer experts on the panel but that he still worried about unexpected effects of the device.
"We received virtually no information in our packet, and the information I saw today did not make me feel any more confident," he said.
Antibodies to rhBMP2
Dr. Rohr was concerned that 2 patients developed antibodies to rhBMP2. "I can't tell from the data if the sponsor has presented whether or not there is an effect related to the immune system, and without this information I cannot personally feel that this is a safe drug."
Asked by panel chair John Kelly IV, MD, from the University of Pennsylvania, Philadelphia, whether a change in the labeling to reflect this potential risk might cause him to change his no vote to a yes, Dr. Rohr replied, "A change in the labeling would not change my decision. A drug is safe or it is unsafe or it is safe at a certain concentration. Labeling doesn't change that fact."
Another naysayer to all 3 voting questions was Raj Rao, MD, from the Medical College of Wisconsin, Milwaukee. "For all 3 questions it boils down to a question of marginal increase in efficacy of the product vs the potential high risk of adverse effects from the product. I based my decision on a relative risk-benefit ratio, and that explains my 'no' vote."
Hollis Potter, MD, from the Hospital for Special Surgery, New York City, said she did not feel that the risk-benefit ratio was adequate because of the lack of data on heterotropic ossification and thecal sac encroachment. "For a BMP product, I think that is necessary."
John Kirkpatrick, MD, from the University of Florida College of Medicine, Jacksonville, said he voted no about efficacy because he could not tell from the data that the sponsor presented who would be good candidates for the new device. He suggested that Medtronic continue to follow up the patients already enrolled in their trials and follow them up for the development of any adverse events. "This will give us a better sense of the safety and efficacy of this device."
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Cite this: FDA Devices Panel Gives a Reserved Yes to Medtronic's Amplify - Medscape - Jul 28, 2010.