Surprising Results Force Medtronic to Halt U.S. Trial of Renal Denervation for High Blood Pressure

Medtronic Inc. has discontinued development in the United States of what many industry-watchers considered one of the most promising potential therapies for patients with high blood pressure that cannot be controlled by medication.

The company ended a large U.S. trial for its Symplicity renal denervation system, which has been designed to control hypertension by burning nerves in the kidneys. Similar to angioplasty, renal denervation involves snaking a catheter through the femoral artery up to the renal arteries, where it uses heat to deactivate the renal nerves and, in theory, lower blood pressure.

“Symplicity HTN-3 met its primary safety endpoint related to the incidence of major adverse events one month following randomization and renal artery stenosis to six months,” said Deepak L. Bhatt, M.D., executive director, Interventional Cardiovascular Programs, Brigham and Women’s Hospital Heart and Vascular Center, professor of medicine, Harvard Medical School, and co-principal investigator of the trial. “Importantly, however, the trial did not meet its primary efficacy endpoint.”

Bottom line, based on the most recent study findings, the company said the technology was ineffective.

While certainly a blow for the Minneapolis, Minn.-based medtech behemoth, the news has a wider industry impact and puts in doubt the future of renal denervation, and what analysts predicted could become a $2 billion to $3 billion worldwide market. Along with Medtronic, companies such as St. Jude Medical Inc., Boston Scientific Corp. and Covidien plc (and dozens of smaller companies around the world) have been competing to take advantage of the prospective therapy.

According to Medtronic, roughly 1.2 billion people worldwide suffer from high blood pressure and about one-third of them have a kind that doesn’t respond to medications.

In addition to ending the trial, which involved 535 patients at 87 medical centers throughout the United States, Medtronic will stop recruiting patients for clinical trials in Japan and India. The company plans to brief medical investigators and patients about the findings and advised that patients should consult with their physician regarding any questions they may have about their treatment.
Follow-up for all patients randomized in the trial will continue as planned out to five years.

As part of the trial, people receiving the investigational treatment were compared with a sham-control group that did not receive treatment, with all patients continuing to take their blood pressure medications. Patients enrolled in the trial were randomly assigned to a group, with two out of three assigned to the treatment group and one out of three assigned to the sham-control group. In addition, those in the control group had the option to receive the treatment after the six-month assessment of the primary endpoint. The primary endpoints of the study are the change in office blood pressure from baseline to six months and incidence of major adverse events.

Based on these clinical trial findings, Medtronic intends to formulate a panel of independent advisors made up of physicians and researchers who will be asked to make recommendations about the future of the global hypertension clinical trial program, as well as provide advice on continued physician and patient access to the Symplicity technology in countries with regulatory approvals. In the meantime, Medtronic will continue to make the device available to overseas patients in countries. The company also plans to continue the global post-market surveillance registry and renal denervation studies evaluating other non-hypertension indications.
Though renal denervation is not a big part of Medtronic’s overall portfolio, the company’s brass had been an enthusiastic early proponent of its potential.

“We are disappointed that the clinical trial failed to meet its primary efficacy endpoint,” said Rick Kuntz, Medtronic’s chief medical officer. “We believe this course of action is the most prudent and will help us thoroughly evaluate these findings and determine the appropriate next steps for renal denervation therapy. We would like to thank the patients and investigators for their participation in the trial and their important contribution to the field of hypertension research.”

Medtronic paid $800 million in 2010 for a company called Ardian and its renal denervation technology.

Danielle Antalffy, with Leerink Swann Research, said Medtronic’s news came as a surprise, following positive results from earlier, smaller clinical trials and in Europe.

“The failed Symplicity HTN-3 trial could also have implications for the [renal denervation] market more broadly, bringing into question whether the catheter ablation approach is truly efficacious in reducing hypertension,” she wrote in a note to investors.

Last year, St. Jude Medical announced that its EnligHTN renal denervation system safely and effectively lowered blood pressure at six months. In December, however, St. Jude discontinued the trial, citing recruitment challenges. The company said the move was not the result of a safety or efficacy issue with the device or study.

Last year, Natick, Mass.-based Boston Scientific, bought a company, Vessix Vascular Inc., that has developed a renal denervation system that had been approved for use in Europe and Australia.