Results of the pivotal Spyral-HTN OFF MED study presented at the American College of Cardiology's Annual Scientific Session on March 29 demonstrated significant reduction in blood pressure three months after renal denervation (RDN) in patients with unmedicated hypertension, providing positive news for study sponsor Dublin-based Medtronic plc. The results were published simultaneously in The Lancet.

Patients who underwent the procedure experienced no major adverse effects, reported lead author Michael Böhm, chief of cardiology at the University Hospital Homburg/Saar in Germany.

Renal denervation is a minimally invasive technique that targets specific nerves near the kidneys that can become overactive and cause high blood pressure. The procedure typically takes about an hour to perform.

The Medtronic Symplicity Spyral system used in the study combines a flexible multi-electrode catheter with a radiofrequency generator. The catheter is inserted through the femoral artery and into the renal artery where the Spyral uses controlled, low-power energy to deactivate the surrounding renal nerves. Renal denervation does not involve a permanent implant.

The Spyral received breakthrough device designation from the FDA on March 27.

“These exciting results definitively demonstrate that RDN lowers blood pressure, including over the 24-hour period,” said Böhm. The 24-hour reduction is particularly important as risk of cardiovascular events is greater in the late night/early morning time frame, a Medtronic spokesperson explained.

The trial

The study randomized 331 patients with uncontrolled hypertension to either RDN (166) or a sham procedure (167). All participants were either untreated or agreed to forego medication for three weeks before and the three months of the trial.

The trial demonstrated greater than 99.9% superiority for RDN over the sham procedure for its primary endpoints LIST and secondary endpoints LIST.

At three months, patients who had RDN saw a 4.7 mmHg drop in systolic blood pressure and 9.2 mmHg decline in office blood pressure. The lower levels were maintained throughout the full day and night.

A previous study showed that a reduction of 10 mmHg in office systolic blood pressure, similar to that seen in the SPYRAL HTN-OFF MED study, reduces coronary heart disease events by 20% and stroke by 27% reduction. A 2 mmHg drop in blood pressure correlates to a significant mortality risk reduction, noted Dave Moeller, Medtronic vice president and general manager of the coronary and renal denervation business.

While significant, the study results likely understate the true antihypertensive effect of renal denervation, Böhm noted.

The ongoing ON MED study and Medtronic’s 2,000 patient Symplicity Registry support that assertion. Both have shown that RDN continues to reduce hypertension over time, but safety considerations kept the OFF MED study to three months.

The market implications

About one in three American adults and more than one billion people worldwide have hypertension. That number is expected to grow to 1.6 billion by 2025, according to Medtronic. That will create a global market opportunity of $1 billion by 2026, with about half of the market in the U.S., Moeller said in an investor call following the ACC presentation.

“As many patients with uncontrolled hypertension struggle to adhere to lifelong drug therapy for a variety of reasons and may look to other options that complement traditional treatments, we believe this advance could help clinicians work with patients to better manage their high blood pressure,” said Moeller.

“In spite of the availability of drugs, two-thirds of diagnosed patients remain uncontrolled. So I think this really highlights the need for an alternative tool to fight hypertension,” he noted.

Renal denervation would particularly benefit patients who can’t achieve control despite the prescription of guideline-based approaches, who are at high baseline cardiovascular risk, or who are unable or unwilling to adhere to medication, a Medtronic spokesperson told BioWorld.

While the company plans to pursue broad labeling upon approval of RDN, physicians will likely first recommend the procedure for patients who have trouble controlling blood pressure despite the use of multiple medications and then expand to those taking fewer medications.

Translating those potential benefits into regulatory approval and sales, however, has been held up by the COVID-19 pandemic which has paused the Spyral HTN-ON MED study that began in November 2018. That study will follow up to 340 patients at 55 centers around the world for up to three years.

The company plans to submit the ON MED data with the current study results to the FDA. Medtronic was on track to complete ON MED enrollment in mid-2020 and have results next year, but the timing now is less certain.