|The Diam Spinal Stabilization System--Courtesy of Medtronic|
The FDA's orthopedic and rehabilitation devices advisory panel unanimously recommended rejection of Medtronic's Diam spinal stabilization implant on Feb. 19. saying its clinical trial data was not rigorous enough to warrant approval. The FDA typically follows the advice of panels when assessing PMA applications, though it is not obligated to do so.
The Diam's proposed patient population includes those with moderate low back pain secondary to single-level symptomatic lumbar degenerative disc disease, according to the meeting documents. "It was designed to treat patients that have not progressed down the degenerative disc disease continuum sufficiently to warrant more complex invasive procedure such as a disc replacement or fusion," Medtronic ($MDT) said in its executive summary.
"I think the primary endpoint, as I pointed out, is mixed up and flawed with respect to its applicability to both arms. The proper emphasis on the intent-to-treat analysis was not done," Brent Blumenstein of Trial Architecture Consulting in Washington D.C. told Healio.
Like Blumenstein, Dr. Harvey Smith of the University of Pennsylvania voted against the Diam on all three questions related to its safety, efficacy and risk-reward profile.
"I did not think there was substantial evidence to say it was definitively safe when we do not entirely understand the mechanism of the spinous process resorption, and given the fact that it was a relatively early follow-up and the nature of the device, that was a concern from the safety perspective, in my opinion," he told Healio. Smith also expressed concerns about animal model data showing the potential for a reaction to the device.
Four panel members voted in favor of the Diam when asked if there was reasonable assurance of safety, as opposed to 7 who said there is not. The panel said the implant failed to demonstrate reasonable assurance of efficacy of by vote of 8 to two, with one abstention. And 7 panel members said the risks of the device outweighed its benefits, while 4 abstained, the FDA said. The last question is used to determine whether panel ultimately recommends acceptance or rejection of a PMA application.
The FDA had already expressed skepticism about the Diam in its executive summary of its PMA application, which it distributed prior to the panel meeting, as usual. The summary said that the device's clinical trial population was heterogeneous because it consisted of patients varying spinal pathologies. "Consequently, data related to subjects with these different spinal pathologies may not be poolable, and the Agency does not agree with the sponsor's conclusion that the results are poolable based upon a post hoc analysis showing comparable treatment effects in each identified subgroup," the agency said.
Medtronic said that using the Oswestry Disability Index, the device had a success rate of 69.1% compared to 17% among the 50-person control group, who received nonoperative treatment, such as medications or physical therapy. In addition, the Diam was found comparable in safety to the control treatments, according to the company.
But FDA wrote prior to the meeting that "in the context of the proposed target population, as well as the Agency concerns pertaining to the study population and nonoperative control group, it is unclear if the definition of the primary effectiveness endpoint and the assessment of overall success at 12 months are adequate."
Unfortunately for Medtronic, the panel did not provide the clear affirmation of the Diam's safety or efficacy needed to clear up the uncertainty, making rejection likely, even though the device earned European CE mark approval more than 10 years ago, and is sold in several countries around the world.
During the second quarter of fiscal year 2016, Medtronic spine device revenues fell 4% year-over-year to $719 million (they were unchanged when adjusting for exchange rate fluctuations). Sales rose 5% outside the U.S., but fell 2% inside of the country.
- read the Healio article