Medtronic is sponsoring a series of new clinical tests of its controversial genetically engineered bone-growth product Infuse in an effort to gather long-term data about the optimal dose of the chemical in fusing spine bones to treat lower back pain.
Back pain is one the most common reasons Americans visit the doctor, and Infuse has been used widely to fuse bones that are painful when they move. But since the product was first approved in 2002 by the Food and Drug Administration, spine surgeons have mainly used Infuse in surgical applications that were not considered for safety by the FDA, including surgeries from a rear or “posterior” surgical approach, according to peer-reviewed studies.
Now Medtronic wants to gather data on two of the unapproved procedures: PLF, or posterolateral fusion of lower-back vertebrae using fixation hardware that attaches to the back of the bones; and TLIF, or transforaminal lumbar interbody fusion, in which a device is placed between the vertebrae being fused. Both experimental surgeries will use the chemical component of Infuse, a highly concentrated version of the naturally occurring human protein that causes bone growth.
Medtronic officials said Tuesday that the first of a planned 125 patients has been enrolled in the Infuse dosing study for PLF, which will be followed by the dosing study next year for TLIF.
If the studies are successful they may lead to larger “pivotal” studies and eventually submission to the FDA for expanded product approvals. Infuse has been used in more than 1 million patients since 2002.
“Infuse is one of the most extensively researched biologic agents commercially available today and Medtronic continues to invest in research of Infuse to deepen the understanding of the benefits and risks of this novel treatment,” Doug King, Medtronic’s spine division president, said Tuesday in a news release.
Infuse has been hailed as a way to create dependable fusions and avoid a second surgery to harvest bone-graft material from the hip bone, but critics say the biologic product creates unique risks and costs and Medtronic has not always been forthcoming in telling doctors what it knows. The product was the subject of a critical U.S. Senate committee investigation, and was featured in a special issue of the Spine Journal that questioned the integrity of past company-sponsored Infuse research.
The FDA warned the public about life-threatening swelling risks from using Infuse in neck-spine surgery in 2008, and sent a second warning in 2015 about using Infuse in patients whose bones are still growing.
The Minnesota-run medical device maker is in the process of settling thousands of Infuse patient-injury lawsuits and resolving five state investigations of Infuse, and in June it settled a racketeering lawsuit with insurer Humana over marketing allegations.
The company has denied wrongdoing in each of the civil cases, and said that it only markets Infuse for FDA-approved applications. It is legal for doctors to use medical devices in unapproved ways because the FDA does not regulate the practice of medicine.
Although Infuse may have an uncommonly controversial history as a medical product, it is common for medical-device companies to launch new studies of older devices and products.
Joe Galatowitsch, a Minneapolis-based managing director with the med-tech practice at consulting firm Navigant, said it’s not only common, but a “best practice” for device companies to continue developing new clinical data about specific uses of devices after the initial FDA approval or clearance.
Galatowitsch couldn’t specifically address Infuse, but in general terms, he said the clinical community may sometimes quickly adopt unapproved uses of a new device, and then have to pull back a bit as the manufacturer works to provide the best clinical evidence it can. In those situations, there may be a stronger desire to develop new evidence when the product use is concentrated in unapproved procedures.
“When the clinical community and industry and the regulatory bodies together see that a given medical technology is being used far removed from its initial indication, there is a sort of a shared responsibility of all three parties to say, ‘How do we think about learning more about the use of this technology in these far-flung use cases that were never really studied in a great amount of detail?’ ” Galatowitsch said.
In 2010, a study in the journal Spine found that 85 percent of the 340,000 inpatient Infuse procedures between 2003 and 2007 were done off-label.
The studies announced Tuesday will last up to 10 years. The first will be an open-label study focusing on PLF patients who need at least three bones fused between the sacrum and the L2 spine bone. Patients will be randomized to one of four treatment groups: a control group getting fusions without Infuse, and three groups getting different doses of the product ranging from 4.2 milligrams to 12 milligrams per level of vertebrae fused.
Past studies have examined larger doses. A 2007 study, supported with a research grant from Medtronic, examined 12-milligram doses of Infuse in posterolateral spine fusion and found the procedure success “compelling” even though it used less Infuse than other surgeries.
Medtronic spokesman Eric Epperson on Tuesday noted that the company did not formally sponsor the 2007 study, but it hopes that the new work “will lead to expanded indications and provide surgeons with additional options to help alleviate pain for more patients.”