Over a two-day-long FDA meeting, an agency panel of advisors considered dueling proposals for new renal denervation therapies—ultimately handing a thumbs-up to Otsuka’s ReCor Medical division, while delivering a narrow thumbs-down to industry giant Medtronic.
Both companies hope their approaches will compete in what they believe can become a multibillion-dollar market, with each looking to offer a drug-free, single-shot procedure designed to make a dent in stubbornly high blood pressure that has not responded to traditional medications.
Renal denervation aims to burn out or disrupt overactivity in the nerves that line the blood vessels leading to the kidneys. By weakening the signals they send out to the brain and cardiovascular system, the approach seeks to take some weight off the gas pedal that fuels drug-resistant hypertension, and with it, higher lifetime risks of heart disease and stroke.
Though both Medtronic and ReCor have already obtained green lights in Europe, it has been a long road to bring the therapy to U.S. shores. Both developers have seen their devices miss endpoints in clinical trials: Medtronic suffered a setback in 2014 with an earlier version of its current hardware, while ReCor more recently failed to meet its target in a clinical trial conducted in Japan and Korea.
However, they’ve each also seen their share of successes. With its redesigned Symplicity Spyral ablative catheter, Medtronic returned in 2020 to demonstrate average drops of 6.5 mmHg in systolic blood pressure three months after the procedure. More recently, three-year data showed that 83.3% of treated patients reported systolic blood pressure of under 140 mmHg, versus 43.8% in a sham control group, after logging baselines of above 150 mmHg.
Meanwhile, ReCor—which Otsuka acquired in 2018—posted a study in 2021 demonstrating 8 mmHg reductions in daytime systolic blood pressure after two months. The company’s ultrasound-powered Paradise system uses sonic energy to create heat while moderating it with a water-filled balloon.
This week, both companies made day-long pitches while their devices sit before FDA reviewers. The agency’s cardiovascular device advisory group unanimously agreed that Medtronic and ReCor’s devices should each be considered safe, but the panel’s members—including experts gathered from academia, medical centers and the industry nationwide—appeared less convinced that they were effective.
ReCor’s Paradise system received an 8-to-3 vote agreeing that it had demonstrated efficacy, as well as a 10-to-2 vote that its benefits outweighed the risks.
Medtronic’s Symplicity Spyral, however, received a much slimmer vote in favor of effectiveness, at 7-to-6. After a 6-to-6 tie on whether the benefits outweighed the risks, with one abstention, the panel chair broke the deadlock with a vote against making a recommendation for approval.
"We appreciate the robust conversation that occurred prior to the vote," Jason Weidman, president of Medtronic’s coronary and renal denervation business, said in a company statement after the meeting. "We will continue to collaborate with the FDA on bringing a new option to the millions of people living with high blood pressure."
Advisory panel recommendations are not make or break but are usually followed by the FDA as it considers additional data before making a final decision on a device’s clearance.
In two major, randomized and controlled studies submitted to the agency, Medtronic tested the Symplicity Spyral in two sets of patients: those who stopped taking their blood pressure medications three to four weeks before undergoing the procedure and stayed off them for three months; and those who maintained a stable drug regimen for at least six months following surgery.
The off-medication study met its primary effectiveness endpoint in reducing average blood pressure measurements, while the on-medication study did not.
According to the FDA’s view, delivered in a briefing document (PDF) to the advisory panel, the latter study’s findings could have been muddled by medication changes and the timing of when participants took their pills compared to when their blood pressure was measured. Medtronic also said (PDF) that missing ambulatory blood pressure measurements could have tipped the scales disproportionately in favor of the control group.
In discussing their votes, panel members did express some confidence in Symplicity Spyral’s clinical benefit, but said it would be helpful to better define which patient subgroups would be most likely to see gains before granting it a broader approval.
ReCor, meanwhile, had presented data from three randomized, controlled studies, including participants both on- and off-medication. Similar to Medtronic, the company’s two off-med trials met their endpoints while the on-med study did not; it demonstrated an average difference in blood pressure reduction of 4.5 mmHg, but the findings were not considered statistically significant.
That difference between the Paradise and control groups narrowed after patients were unblinded and treated further with antihypertensive drugs, though the FDA noted (PDF) that untreated patients trended toward higher reliance on medications to help meet their blood pressure goals.
“We will continue to work closely with the FDA in advance of our anticipated PMA approval and feel confident in the impact that Paradise Ultrasound RDN could have in addressing a significant unmet need,” ReCor Medical President and CEO Lara Barghout said in a statement.