Medtronic Inc.’s experimental spinal fusion device Amplify didn’t work as well after five years as it did in two-year tests previously reported by the company, according to U.S. regulators weighing its approval for sale.
After two years, surgeries were successful in 61 percent of Amplify patients, compared with 56 percent for those who had standard procedures using a bone graft from the hip, the Food and Drug Administration said today in a report. Amplify resulted in successful operations in 44 percent of patients after five years, compared with 35 percent for standard care, the agency said. A higher number of cancer cases were seen in the Amplify group, FDA reviewers said in the report.
Medtronic, the world’s largest maker of heart-devices, has been trying to reinvigorate growth in its spinal products business, which accounted for 22 percent of the Minneapolis- based company’s $15.8 billion in revenue for its 2010 fiscal year ended in April. Spine division sales grew 3 percent to $3.5 billion last year. If approved, Amplify may add as much as $175 million, or 8 cents a share, to earnings in its first year, Leerink Swann analyst Rick Wise said in a research report today.
“We now put the likelihood of a positive panel recommendation at just 40 percent,” Michael Weinstein, a New York-based analyst at JPMorgan Securities, wrote in a note to investors today. “Cancer risk could trip up approval.”
After two years, 3.8 percent of Amplify patients had cancer, compared with 0.9 percent on standard surgery. The malignancy rate for Amplify increased to 5 percent after five years, compared with 1.8 percent for traditional grafts, according to the FDA report.
Medtronic shares fell 19 cents to $36.58 at 4:15 p.m. in New York Stock Exchange composite trading. The stock has increased 6.4 percent in the past 12 months.
Outside advisers to the FDA will meet July 27 to evaluate Amplify. The agency generally follows the recommendations of its advisory panels, though it isn’t required to do so.
“At the panel, we will present preclinical and clinical study data, along with expert opinion, that no plausible biological mechanism for cancer induction or promotion has been identified,” Medtronic spokeswoman Marybeth Thorsgaard said in a July 21 telephone interview.
The five-year rates don’t show a statistically significant increase in cancer rates between the two study groups, Weinstein wrote in the note. “However, the documents do note that this numerical difference comes close to reaching significance with the FDA describing it as ‘borderline,’” he wrote.
The advisers will focus on the clinical and statistical significance of cancer rates, especially pancreatic cancers, in current studies and determine whether additional evaluations are needed, the FDA said in its report.
The panel also will look at how the overall surgical success rates for the two study groups were determined and at a greater number of serious back and leg pain side effects reported by patients in the Amplify group, according to the documents. A successful surgery was defined as an operation in which the vertebrae or bones were joined together and stabilized.
About 660,000 back surgeries were performed in the U.S. in 2009, according to Millenium Research Group, a medical market research company in Toronto. In spinal fusion surgery, doctors use bone grafts in an area of the spine to lock together, or “fuse,” the area between two or more vertebrae to treat back pain cause by spinal disease and injuries.
A standard spinal-fusion procedure requires two surgeries, often done at the same time, Martin Yahiro, Medtronic’s senior director of clinical and regulatory affairs, said in a July 21 telephone interview. First, doctors operate to take a section of hip bone for use as a graft for the second procedure that repairs the spine, he said.
Amplify combines the company’s bone growth protein, known as rhBMP-2, with a ceramic device implanted in the spine for posterior spinal fusion through the patient’s lower back. The bone protein, marketed as Infuse, won U.S. approval in 2002 for anterior fusion surgeries, a lower-back operation performed through an incision in the front of the patient. It is also cleared for dental procedures and to repair lower leg fractures.
Infuse generates as much as $800 million in annual revenue for Medtronic, with sales unchanged the past two years, Weinstein said.
The Amplify product uses a higher dose of the bone mineral protein than the Infuse device, the FDA staff report noted.
In the two-year study of 463 patients that Medtronic used to seek approval of Amplify, those treated with the device had shorter surgical times, less blood loss, and needed fewer repeat operations compared with those who had the standard procedure, according to results published in July 2009 in the Journal of Bone and Joint Surgery.
If the FDA decides to approve Amplify, Weinstein said it is likely to require a large study after the product goes onto the market to assess cancer risk.
“The FDA is saying that the historical data on Infuse safety is of limited significance because you’ve upped the dosing by three times,” Weinstein said in a telephone interview. “So even if there’s not a significant cancer risk with Infuse, you’ve tripled the dosage and how do you get the FDA panel comfortable with that?”
Amplify’s advantage “seems to boil down to saving 20 minutes in the operating room,” said Richard Deyo, a spine expert at Oregon Health & Science University in Portland, in a July 21 telephone interview. Complications from the hip bone grafts “should not be trivialized but it’s not clear to me that there is a big problem there.” Deyo was not involved in Medtronic’s study.