Therapy focus – the denervation derby

Data Insights

The small but significant treatment effect demonstrated by Medtronic’s renal denervation device in a trial reported last week has reignited excitement around the hypertension therapy. With Medtronic plunging straight into a pivotal study in an attempt to reach the US market at last, its competitors will surely be thinking about the potential of their own devices.

A look at the handful of clinical trials being actively pursued shows three of the big names in interventional cardiology – Medtronic, Abbott and Boston Scientific – leading the charge (see table below). Many of these studies are hangovers from before the technique was discredited in 2014, and the groups’ decisions to carry on with them quietly might just pay off.

The nerve of it

Renal denervation is intended to treat drug-resistant hypertension by scorching the nerves in the wall of the renal artery using radiofrequency electrodes, which are mounted on catheters and threaded through the vasculature. Attenuation of the nerves limits activation of the sympathetic nervous system, which has been proven to lead to high blood pressure.

Interest in the technique faded after the failure of Medtronic’s initial pivotal US trial – the first to use a sham control procedure – three years ago (Failure of Medtronic’s Symplicity trial exacerbates concerns over renal denervation, January 9, 2014). But early, interim data that emerged recently from a trial of Medtronic’s new system might just put renal denervation back on the menu (ESC 2017 – The corpse of renal denervation starts twitching, August 28, 2017). 

So which other groups might be in a position to capitalise on renal denervation’s rehabilitation? 10 active industry-sponsored trials are ongoing, and some could yield data in short order. The analysis below only includes trials verified since the beginning of 2017, while studies for conditions other than hypertension – the technique is also under investigation for cardiac arrhythmias, for example – have been excluded.

Selected ongoing trials of renal denervation devices
Company Device Study Enrolment Primary completion date Trial ID
Abbott EnligHTN EnligHTN-II 354 May 2017 NCT01705080
Abbott EnligHTN CV-12-064-GE-HT 25 May 2017 NCT01996033
Abbott EnligHTN CV-12-064-EU-HT 68 August 2017 NCT02006758
Medtronic Symplicity Spyral Spyral HTN-On Med 100 September 2017 NCT02439775
Medtronic Symplicity Global Symplicity registry 3,000 November 2017 NCT01534299
Boston Scientific Vessix Reduce HTN:Reinforce 100 February 2018 NCT02392351
Ablative Solutions Peregrine Peregrine post-market study 120 March 2018 NCT02570113
Medtronic Symplicity Spyral Spyral HTN-Off Med 170 July 2018 NCT02439749
Recor Medical Paradise Radiance-HTN 292 August 2018 NCT02649426
Symap Medical SyMapCath Smart 212 December 2018 NCT02761811
Source: EvaluateMedTech and Clinicaltrials.gov.

The first trials that could report – if Abbott chooses to reveal the data – are investigating the company’s EnligHTN denervation catheter. These were begun by EnligHTN’s originator, St. Jude Medical, but their listings on clinicaltrials.gov suggest that Abbott has not let them lapse.

However, they are European postmarket trials so will not move the company any closer to the US, but more importantly none includes a sham control group; they will therefore be unable to demonstrate EnligHTN’s effectiveness definitively.

Spyral HTN-On Med is the sister study of Spyral HTN-Off Med, interim results from which restarted the whole shebang at the ESC meeting. Data from On Med could emerge early next year, and as it is a US-based investigation with a sham group, positive data will back Medtronic’s decision to forge ahead with the approval trial. Full data from Spyral HTN-Off Med, meanwhile, will not arrive until late 2018, and are keenly awaited.

Unlike Abbott, Boston Scientific might soon find itself in a position to challenge Medtronic for the US market. Its Vessix device is in a sham-controlled US study due to read out next spring, and if data are positive a pivotal study could well be on the cards.

Breaking America

Ablative Solutions is taking a novel approach to denervation: its Peregrine catheter does not emit radiofrequency energy but instead infuses a neurolytic agent into the perivascular space surrounding the renal artery, targeting the sympathetic nerves. The device was CE marked in 2015, and it is now in a single-arm post-market European study.

Recor Medical is making a serious attempt at breaking America. Two weeks before the Off Med data were reported Recor obtained $12m from its exiting investor Otsuka Pharmaceutical to go towards the major US trial it kicked off last year (Recor hopes to find Paradise on the market, March 15, 2016).

Though Radiance-HTN is sham-controlled, it will not be sufficient to get FDA approval for Recor’s Paradise catheter as it is powered for efficacy but not safety. But a successful conclusion late next year will surely mean that a pivotal trial will follow.

Little is known about the Chinese group Symap other than that it is part of the venture investor Sequoia Capital’s portfolio. Its SyMapCath I system does not seem to be CE marked, but this could be because the company is focusing on its home market; the Smart trial is recruiting more than 200 patients at several sites in China.

Despite having the studies that will read out first – indeed, two may already have done so – Abbott is behind the curve when it comes to finally bringing renal denervation to the US. Medtronic, Boston and Recor are the ones to watch. In light of the Spyral HTN-Off Med data Abbott might want to weigh up starting sham-controlled US trials of EnligHTN. It bought St. Jude for its cardiovascular technologies, after all, and it will surely not want to be left behind.

To contact the writer of this story email Elizabeth Cairns in London at elizabethc@epvantage.com or follow @LizVantage on Twitter

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