Medtronic Inc.’s Infuse, designed to help bones heal after spinal surgery, works no better than a graft and carries side effects including an increased risk of cancer, two independent reviews found.
The studies published in the Annals of Internal Medicine may help doctors weigh when to recommend the product, used in more than 1 million patients. The $2.5 million review of Infuse was commissioned by Minneapolis-based Medtronic in 2011 after the product’s risk-benefit profile was called into question by research linking it to male sterility, infections and cancer.
The most recent studies carry a mixed message that needs to be carefully explained so patients “can make informed choices about the type of surgery they would prefer,” the researchers wrote. While Infuse is less invasive than a bone graft, which can require a separate surgery, the rise in cancer rates and other potential risk are worrisome, they said.
“I remain concerned that products like these are approved with too little study before they reach the market and too little afterward,” Harlan Krumholz, the Yale University professor who was in charge of the project, said in a telephone interview. “There is a tremendous amount of uncertainty about the benefit it provides and how safe it is.”
Medtronic, the world’s biggest maker of spinal treatments, fell 1.1 percent to $52.92 at the close in New York. The shares have gained 39 percent in the past 12 months.
Infuse was the first product reviewed as part of Krumholz’s Yale University Open Data Access project. The information on Infuse is now contained in databases that other researchers can access and analyze.
Earlier studies that said Infuse was risk-free were marred by reports of financial ties between the researchers and the company, and one of the new reviews found those publications misrepresented the risks and benefits. Chief Executive Officer Omar Ishrak, who authorized Yale University to conduct the review two months after he took the helm at Medtronic, cited it as a key element in the company’s growth prospects.
The latest reviews show Infuse is equivalent or better than the gold standard treatment for spinal fusion, which is bone grafts using material that must first be harvested from the hip, said Chris O’Connell, president of Medtronic’s Restorative Therapies Group.
The rates of cancer were low and the risk from Infuse was inconclusive, O’Connell said. Medtronic is looking for ways to continue studying the product, he said.
“This is a really important product and it’s one that deserves a lot of attention from the standpoint of clinical research,” O’Connell said in a telephone interview.
Infuse is a reasonable treatment for some fusions in the lower spine, wrote Daniel Resnick from the University of Wisconsin and Kevin Bozic, from the University of California, San Francisco, in an editorial that accompanied the research released yesterday.
It shouldn’t be used at the top of the spine, where it isn’t approved, without a compelling reason because of higher complication rates, they said. The small and perhaps temporary increased risk of cancer should be evaluated for each patient, they said in an editorial accompanying the reviews.
The role of Infuse “in spinal surgery is still being defined,” according to the editorial. “Clinicians should carefully weigh the demonstrated and potential benefits and harms as well as the costs when considering the adoption and use of new health care technologies.”
Sales of Infuse may dip, primarily because of the increased risk of cancer noted in the report, said Derrick Sung, an analyst with Sanford C. Bernstein. Analysts projected future declines in Infuse revenue notes to clients today, though they varied with how steep the drop will be.
“Most surgeons are well aware of the risks associated with Infuse and have years of personal experience on which to base their assessments of efficacy,” Sung wrote. “Our sense is that most surgeons have made up their mind around appropriate usage of Infuse,” he said. “The negative finding around increased cancer risk somewhat outweighs the positive finding around the lack of other adverse events.”
Infuse, which generated $528 million worldwide in the year ended April 26, accounts for 3 percent of the company’s business, Ishrak said at the Bernstein Strategic Decisions Conference on May 31.
The product is unlikely to return to the widespread use of earlier years, when orthopedic surgeons were giving it so often that it was unclear which procedures had regulatory approval, said Joanne Wuensch, a New York-based analyst at BMO Capital Markets. Infuse’s sales have plunged 37 percent since its $221 million peak in the first quarter of 2009.
“It became like the magic sprinkle powder in orthopedic and spinal surgeries, and other operations throughout the body,” Wuensch said by telephone. “I don’t think we ever go back to that. The physician’s market has right-sized itself.”
While there are rival products from Nuvasive Inc. and Johnson & Johnson’s Synthes unit, they haven’t been rigorously studied in the same patients and don’t have the same approvals from U.S. regulators, she said.
Doctors administered Infuse for a variety of conditions, believing it carried few side effects, according to the reports released today. While the bone growth protein is approved for tibia fractures, facial surgery and fusing damaged vertebrae in the lower spine, it was widely used in the upper, cervical spine and other areas, doctors said.
The Yale review analyzed findings from two research groups, one at the Oregon Health & Sciences University in Portland and the University of York in the U.K. The two groups were given detailed data from 17 spinal studies using Infuse on more than 2,000 patients, as well as safety reports given to U.S. regulators and other publications about the product.
The Oregon review found that Infuse was similar to bone grafts in overall success, fusion rates and risks when used in lumbar spine fusion, though some published studies incorrectly said Infuse performed better.
For other types of surgery, Infuse patients had higher, though not always significant, increases in retrograde ejaculation, urogenital problems, bone spurs that can cause nerve pain and wound complications.
“We couldn’t find a clear advantage in terms of benefits, and when you take into account there could be potential risks that should be more carefully evaluated, it tips the scales toward not using it,” said senior author Mark Helfand, an internal medicine specialist at OHSU, in a telephone interview.
The review from the University of York found fusion rates were better after two years with Infuse, with more early pain and less later pain. Cancer occurred in a small number of people and may have been more common with Infuse. The results weren’t definitive and studies may have been biased, researchers said.