Medtronic Infuse Controversies Include Questions Over Cancer Risks

Medtronic Infuse Controversies Include Questions Over Cancer RisksMedtronic Inc.’s Infuse Bone Graft product has been a subject of controversy since roughly 2008, but this past fall, concerns about the bone growth product deepened when a prominent spine researcher revealed that Infuse may pose a higher cancer risk than first thought. According to Dr. Eugene Carragee, a Stanford University School of Medicine professor and editor of the Spine Journal, research he conducted indicated that patients who underwent procedures using Infuse more than doubled their cancer risk within one year of use. The cancer risk grew to almost five-fold after three years, he said.

According to a report from Reuters, the cancers cited by Carragee’s study included pancreatic, breast and prostate cancers. Carragee presented his Medtronic Infuse study this past November, during the annual North American Spine Society meeting in Chicago. His analysis pooled clinical trial data from Infuse, and a high-dose version of the same protein, Medtronic’s Amplify, which the U.S. Food & Drug Administration (FDA) refused to approve last year because of concern over cancer risks, Reuters said.

Medtronic Infuse Background

Infuse Bone Graft contains recombinant human Bone Morphogenetic Protein (rhBMP-2), a protein released naturally by the body that promotes bone growth. It is approved to treat a spinal condition called Degenerative Disc Disease, as well as open fractures of the tibia. It is also approved for use in two dental bone grafting procedures: sinus augmentation and localized alveolar ridge augmentation. In 2008, the FDA warned that Infuse and similar products had caused serious and potentially life-threatening problems when they were used off-label in cervical spine (neck) surgeries. Despite such dangers, it is believed that 85% of the procedures using Infuse are off-label.

Over the summer, an entire issue of The Spine Journal dedicated to rhBMP-2 raised serious questions about the validity of the research that was used to gain FDA approval of Infuse. One of the articles included in the journal, co-authored by Carragee, found that Medtronic-paid surgeons had failed to report serious complications from Infuse, including cancer, sterility in men, infections, bone dissolution and worsened back and leg pain. The Spine Journal article said complications occurred in 10 to 50 percent of patients who got the product in 13 Medtronic-funded clinical trials between 2000 and 2010. Medtronic Infuse injuries reported by The Spine Journal included

  • Ectopic or uncontrolled bone growth at or near the site of the surgery
  • Ongoing or chronic radiating pain in the legs or arms
  • Male sterility, retrograde ejaculation, or other uro-genital injuries
  • Nerve injuries causing severe and chronic pain
  • Cancer

Medtronic Infuse Cancer Study

According to a report from The New York Times, the analysis of Medtronic trial results Carragee presented in November showed a significantly higher number of cancers in the study group that received Amplify when compared to a control group that received a bone graft as part of a spinal fusion. At three years after surgery, there were 20 cancers in the Amplify group versus five cases in the bone graft group. C

Carragee pointed out that doctors often administered Infuse off-label at levels significantly above the recommended dosages, ones that approach or exceed the amount of rhBMP-2 found in a dose of Amplify.

“This information requires careful consideration because of the large number of patients receiving high doses” of Infuse, he told the Times. Carragee added that he was particularly concerned about its use in certain patients like smokers or those with genetic factors that put them at higher risk for cancer.

Carragee did note that cancer takes years to develop. His findings, which showed cancer occurring within just a few years of rhBMP-2 implantation, could indicate that Infuse promotes, rather than causes, cancer, he told the Times.

Did Medtronic Hide Amplify Cancer Risk?

There is some evidence that Medtronic may have attempted to conceal Amplify’s cancer association in 2009, when company-sponsored researchers published results from a clinical trial for the product in the Journal of Bone and Joint Surgery. According to an investigation published by the Milwaukee Journal-Sentinel and MedPage Today, as they were preparing to publish the study, the research team discovered that the number of cancer cases among patients treated with rhBMP2 had crossed the threshold for statistical significance. However, this information was left out of the final submitted manuscript. Cancer was only addressed in a single line in a table the accompanied the article, and even then, many worrisome cancers were omitted. The subject of cancer was never brought up in the article’s discussion sections.

According to the Journal-Sentinel and MedPage, Medtronic and the research team have steadfastly maintained that the cancer cases seen in the study were not statistically significant, and that the results from the Amplify clinical trial can’t be applied to rhBMP2 in general, nor to Infuse in particular. However, there was a “full airing of the cancer question in more than 1,000 pages of FDA records. That information included FDA reports and information filed with the agency by Medtronic as part of its application to win approval for Amplify,” the Journal Sentinel and MedPage reported. Why a “full airing” of cancer risks wasn’t made public when the study was published in 2009, while the FDA was made aware of the cancer cases seen among Amplify patients in the same trial isn’t exactly clear.

The Journal Sentinel and MedPage investigation found that first three of the study’s six authors or entities they are associated with received about $10 million from Medtronic, mostly in royalties, in 2010 alone. The royalties, however, were not for BMP2.

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