Medtronic suffered yet another disappointment in its relentless pursuit of bringing renal denervation to market for people living with uncontrolled high blood pressure.
There seems to be no question regarding the safety of the Symplicity Spyral system, but an advisory panel was split Wednesday on efficacy (7 yes, 6 no) and benefits versus risk, a vote that fell 6 to 7 with one abstention.
FDA will ultimately decide the fate of Medtronic’s premarket approval (PMA) submission for the Symplicity Spyral renal denervation system. While the agency doesn’t always follow the advisory committee recommendation on approval decisions, it is rare to see a discordance. A study published in January found FDA only approved a product despite a negative advisory committee vote six times in six years.
What happens if FDA rejects Medtronic's renal denervation submission?
Analysts speculate it will take FDA three or four months to render its decision on Medtronic’s PMA submission for the Symplicity Spyral.
Even if the agency does approve the renal denervation system, the company will have its work cut out for it trying to establish reimbursement for the procedure.
Ryan Zimmerman, a medtech analyst at BTIG, pointed out that Medtronic had previously guided renal denervation to become a multi-billion market, with global market revenue expected to exceed $500 million by 2026 and between $2 billion and $3 billion by 2030, but the company did not reiterate that guidance after disappointing HTN-On Med results were reported last year.
If the device is not approved, the analyst said Medtronic would likely need to run another trial to address some of the concerns and questions raised at the panel meeting.
“This is a disappointing outcome for [Medtronic] but doesn't close the door completely,” Zimmerman wrote.
Wednesday’s panel vote came a day after the same panel voted in favor of Recor Medical’s Paradise renal denervation system (unanimous positive vote on safety; 8 yes votes to 3 no votes and 1 abstain for efficacy; and 10 yes to 2 no votes on benefits/risks).
“The committee’s concerns about Symplicity Spyral seemed to focus on the fact that the [Medtronic] HTN-ON MED trial missed its primary efficacy endpoint, the blood pressure benefit from [renal denervation] was very small, the significant variability of results between patients, and a perceived disconnect between [Medtronic’s] proposed indications for use and the trial designs,” Mike Matson, a medtech analyst at Needham & Co., wrote in his report.
Matson said there was also some discussion about the fact that Symplicity Spyral is classified by FDA as a breakthrough device, but he said he is not sure this will offset the unfavorable vote.
“Given the vote, we think that the FDA is unlikely to approve Symplicity Spyral,” Matson wrote.
Will Medtronic throw in the towel on renal denervation?
To properly speculate on the answer to this question, we must look back at Medtronic’s long and costly renal denervation program and the many disappointments the company has faced along the way.
Medtronic inherited its renal denervation technology through an $800 million acquisition of Ardian in early 2011 under Bill Hawkins, a former Medtronic CEO. Hawkins had pegged renal denervation as a multi-billion-dollar opportunity.
Medtronic’s earlier high-profile renal denervation trial (SYMPLICITY HTN-3) failed in January 2014. Soon after that news broke and well before the Medtronic-Covidien merger, Covidien pulled the plug on its OneShot renal denervation program citing slow market growth in Europe.
Just when the industry had all but given up on the idea of renal denervation as a treatment for resistant hypertension, Medtronic launched a new renal denervation program involving two studies of its Symplicity Spyral catheter and Symplicity G3 radiofrequency generator. That news was encouraging because the first trial had been conducted using a first-generation single-electrode catheter, whereas Medtronic's Spyral device has multiple electrodes to provide mild electronic pulses to nerves in the wall of the renal artery.
Matson said he expects Medtronic to abandon renal denervation if the company fails to win FDA approval this time around.
A statement the company released following the panel vote conveyed a more determined tone, however.
"We appreciate the robust conversation that occurred prior to the vote," said Jason Weidman, senior vice president and president of Medtronic’s coronary and renal denervation business, which is part of the company’s cardiovascular portfolio. "We will continue to collaborate with the FDA on bringing a new option to the millions of people living with high blood pressure."
Why has Medtronic been so relentless on renal denervation?
Hypertension is a thorny condition because it impacts so many people (nearly 1 billion adults worldwide), and it is the leading modifiable cause of heart attack, stroke, and death. While there are hypertension medications on the market to help patients control their blood pressure, nearly 80% of adults with high blood pressure do not have it under control and half of hypertension patients stop taking their medication as prescribed within one year.
"The Symplicity Blood Pressure Procedure has the potential to fill a significant unmet need in hypertension care, and we know patients are looking for options in addition to medication and lifestyle modifications to manage their blood pressure," said David Kandzari, MD, chief of the Piedmont Heart Institute and Cardiovascular Services and lead principal investigator of the SPYRAL HTN-ON MED clinical trial. "The totality of evidence demonstrated that there is a benefit with the Spyral [renal denervation] catheter, and there is no question about the safety of the procedure."
Medtronic says its Symplicity Spyral renal denervation system uses a minimally invasive procedure that delivers radiofrequency energy to specific nerves near the kidneys that can become overactive and cause high blood pressure. The device is already approved in 70 countries around the world, Medtronic noted, but is limited to investigational use in the United States, Japan, and Canada.
Medtronic touts that its SPYRAL HTN global clinical program is the most comprehensive clinical program studying renal denervation for more than 10 years in more than 4,000 patients in the presence and absence of medication, and with high baseline cardiovascular risk.
The Symplicity blood pressure procedure has demonstrated sustained and durable drops in blood pressure out to three years in randomized control and real-world registry trials, the company noted.