Shares of Medtronic Inc. (NYSE:MDT) stock recovered following a week of high-profile publicity around the company’s Infuse bone morphogenetic protein and a Spine Journal issue dedicated to problems with 13 studies by MDT-sponsored physicians.
MDT shares were trading at $38.95 in mid-day activity today, about even with their June 27 open of $38.20 (but down 10.8 percent from a year-to-date high of $43.20).
But even as the furor dies down on Wall Street (where analysts warned of a possible 3-cent-per-share dip in overall profits), Medtronic and Infuse are under intense scrutiny elsewhere. The U.S. Justice Dept. and the U.S. Senate are each conducting probes into the bone morphogenetic compound and its Fridley, Minn.-based maker’s marketing practices.
More significant, however, is the pall cast over the product’s safety. Infuse uses the orthobiologic, known as recombinant human bone morphogenetic protein-2, and an implant to promote bone growth after spinal fusion surgeries. The Spine Journal devoted its entire June issue to an examination of previously published Infuse reports, finding serious and troubling discrepancies between those reports and data from the studies as reported to the FDA, follow-up reports and administrative and organizational databases.
Specifically, the Spine Journal (PDF) authors found that, although the 13 industry-funded reports (published by authors who collectively received millions from Medtronic) reported no adverse events associated with rhBMP-2, the actual rate of "frequent and occasionally catastrophic complications"of between "10 percent to 50 percent depending on approach."
"Anterior cervical fusion with rhBMP-2 has an estimated 40 percent greater risk of adverse events with rhBMP-2 in the early post-operative period, including life-threatening events," the authors wrote. "After anterior interbody lumbar fusion rates of implant displacement, subsidence, infection, urogenital events, and retrograde ejaculation were higher after using rhBMP-2 than controls. Posterior lumbar interbody fusion use was associated with radiculitis, ectopic bone formation, osteolysis, and poorer global outcomes. In posterolateral fusions, the risk of adverse effects associated with rhBMP-2 use was equivalent to or greater than that of iliac crest bone graft harvesting, and 15 percent to 20 percent of subjects reported early back pain and leg pain adverse events; higher doses of rhBMP-2 were also associated with a greater apparent risk of new malignancy."
That’s obviously bad news for Medtronic, which pulls down between $700 million and $750 million from Infuse alone, analysts estimate. The company wasted no time in issuing a spirited public response to the controversy. Newly minted CEO Omar Ishrak said in prepared remarks that “the articles do not raise questions about the data Medtronic submitted to the FDA in the approval process or the information available to physicians today through the instructions for use brochure attached to each product sold.”
"Based on that data, we strongly believe that the safety profile reported to the FDA and summarized in the product label support the safe use of rhBMP-2 for the identified indications," Ishrak said.
Medtronic spokesman Steve Cragle told MassDevice that the company hasn’t "heard any feedback from our customers that they are reducing their expected use." Infuse, Cragle told us, is a "physician-pull product," meaning that Medtronic reps don’t actively promote it and aren’t compensated for any Infuse sales.
"So it’s up to the physician to determine when to use our product," Cragle wrote in an email.
But the confidence of spinal surgeons once accustomed to using rhBMP-2 is undoubtedly shaken from the public beat-down (not to mention the hurdles facing Medtronic’s Amplify product, a higher-test version of the rhBMP-2-based treatment).
It should be noted that Medtronic, more than many companies in the medical device space, has striven to get out ahead of the push for transparency in its financial dealings with doctors (that’s one reason why the incendiary amount of the MDT-sponsored docs’ remunerations was available in the first place). The company isn’t responsible, after all, for what others do with the data generated by the studies. And it’s hard to prove a link between a royalty check from Fridley and the recipient’s use of data from studies of products he or she is not directly involved in.
We live in an age where smells matter. It just doesn’t smell right to have docs on the payroll who conceal or downplay negative clinical evidence, no matter the reason. The coverup, as they say, is always worse than the crime. Medtronic, which logged $3.1 billion in profits last year and is the world’s largest pure-play medical device firm, can likely absorb the fallout from lower Infuse sales.
The Infuse foofaraw has implications that echo far beyond the spinal fusion sector. It calls into question the integrity of a critical step in bringing medical devices to market: Industry-funded trials and how data from them is reported in peer-reviewed literature. Considered the gold standard for clinical evidence, peer-reviewed publication puts a stamp of legitimacy on given med-tech product and is a key plank in the promotion platform companies use to market their wares. If the evidence presented in peer-reviewed publications cannot be trusted, neither physicians nor patients can be assured that they are delivering and receiving safe, effective care.
And that, when all is said and done, is the reason medical device companies exist at all.