Medtronic faces a denervation delay

Medtronic’s unusual strategy of declining to file its renal denervation system when the pivotal study came in positive looks, this week, odder than ever. The company had opted to wait for data from an additional trial, called Spyral HTN-On Med, testing the device in combination with drugs; hopes that this would be stopped early have now been dashed. The group traded down 6% yesterday. 

The Simplicity Spyral is one of the company’s biggest hopes, with management stating that the market could be worth $2-3bn by the end of this decade. The On Med trial will now continue for another year – and will need to show an impressive lowering of blood pressure if Spyral is to be viable. 

The pivotal US trial of the blood pressure treatment, Spyral HTN-Off Med, hit in March 2020, and Medtronic could have gone straight to the FDA at that point. Instead it decided to wait for data from a sister trial, On Med, since this setting better reflects how patients might be treated in the real world. Essentially the group gambled that an interim readout could be added to a filing this year.  

No such luck. On Friday it admitted via an SEC filing that On Med’s independent data safety monitoring board had found no significant difference between the treatment and sham in the first 130 patients in the trial. The board recommended that the trial continue to its full enrolment of 260 patients, with full data now expected in the second half of 2022. 

What kind of magnitude of blood pressure decrease might the trial show? The pivotal trial produced a 24-hour systolic blood pressure drop of 3.9mmHg – but it is possible that On Med might yield a lesser effect.

Omens

This is the pattern seen with a rival product, the Paradise system developed by Recor, now a subsidiary of Otsuka. In the 282-patient non-pivotal Radiance-HTN trial, Paradise yielded a greater effect in the cohort denied antihypertensive medication than it did in those on drug therapy (Otsuka’s denervation system hits in mid-stage trial, May 17, 2021).

A Recor representative told Vantage that note that the patients in Solo had mild to moderate hypertension, whereas the Trio cohort had resistant hypertension. Considering the difficulty of treating this population, the blood pressure drop in Trio is noteworthy.

Comparisons across trials are always imperfect, and clearly the fact that this pattern has been seen with Otsuka’s device does not mean that Spyral will inevitably follow suit. But On Med will have to show a sizeable blood pressure reduction over sham – 5mmHg has been mentioned as an acceptable figure – for the device to meet Medtronic’s sales expectations. 

The pivotal US trial of Paradise, Radiance-II, is expected to report in a similar timeframe to On Med. And here Otsuka might have just received a bad omen. 

A Japan and South Korea-based trial of Paradise, Require, failed to show a significant difference in blood pressure reduction between the treatment and sham groups.

Professor Kazuomi Kario, Require’s principal investigator, said a lack of effective medication stabilisation and adherence “confounded the efficacy signal”. Otsuka says it is working with the Japanese regulators to plan a new randomised, controlled trial in medicated hypertension patients.

Renal denervation was all but dead once before, and managed to find its way back to the light. It would be premature to write the technique off on the strength of the On Med interim look and the Require failure.

But Medtronic’s Symplicity Spyral system will probably not reach the US market until 2023. Had the group sought approval as soon as it could have, the device could already have been available. Sales might have been sluggish, but that surely would have been better than a three-year delay.

This article has been updated to include comments from Recor.