That the pivotal trial of Medtronic’s renal denervation device Symplicity has missed its efficacy endpoint is bad news for the company and also, perhaps, for its competitors. The hypertension therapy was the frontrunner for US approval, leading St Jude Medical’s EnligHTN and Boston Scientific’s V2 system, among others.
Now Medtronic says it will consider not only whether to continue development of the device but also whether to revoke market access in the countries, including the EU, where it is already available. US launch of Symplicity was one of the main planks of Medtronic’s growth strategy, and the loss of it will hurt. But if the trial failure points to problems with the technique – as has been suggested before – rather than Symplicity in particular, Medtronic’s rivals could feel the sting too.
Symplicity works – or is intended to work – by using a catheter tipped with a radiofrequency electrode, inserted via the femoral artery, to attenuate the nerves surrounding the renal arteries; it is withdrawn after the procedure, leaving no permanent implant. The attenuation limits activation of the sympathetic nervous system, which has been proven to lead to high blood pressure. The system, like its rivals, is positioned as a treatment option of patients whose hypertension is not controlled by drugs.
The 535-patient pivotal Symplicity HTN-3 study aimed to show that Symplicity could improve systolic blood pressure, as taken in a doctor’s office, at six months post-treatment, as compared with a sham-control group.
Patients in the control group underwent screening renal angiography, a fairly similar procedure to denervation also requiring femoral access. Medtronic says that the study was the first to include such a group, and suggests, reasonably enough, that HTN-3 is thus the most rigorous trial of a renal denervation system to date.
The company will now put together an independent panel to determine the future of the clinical trial programme and advise on whether access to the Symplicity technology in countries with regulatory approvals should continue. In the meantime, access to Symplicity will continue at doctors’ discretion – but recruitment in pivotal trials in Japan and India, as well as in the Symplicity HTN-4 study in the US, will be halted.
But Medtronic admits that it is not looking good. It says it is “evaluating the carrying value of the renal denervation assets and based on the above trial results, believes a one-time impairment charge in the future will be likely” – corporate-speak for curtains.
The implications for the five other renal denervation systems that have gained CE mark – EnligHTN and V2 as well as Covidien’s OneShot, ReCor Medical’s Paradise and Terumo's Iberis – are sobering.
All claim to be more advanced than Medtronic’s device, with larger or multiple electrodes at the catheter’s tip. But it has been suggested, for instance in a meta-analysis published in Heart in September, that the impressive results seen with various renal denervation systems may be influenced by the lack of blinding or sham control in study design. If this is indeed the case – and the HTN-3 data would seem to bear it out – then all such technologies are in danger.
St Jude in particular is in an odd situation. It called off its pivotal US trial of EnligHTN in December fearing that Symplicity would gain approval and make it too difficult to attract patients. Perhaps it will now restart the study – or perhaps it will decide that it is well out of this area.
Medtronic has been hit first and hit hardest, however; shares were down 3% to $59.33 in early trade. US launch of Symplicity was scheduled for early next year and was expected to have a two- to three-year lead on the competition. Analysts from JP Morgan wrote that US launch of Symplicity could have added around $415m to Medtronic’s FY15-FY17 top line, and that they expected CMS reimbursement to arrive swiftly after launch, resulting in “a significant market developing in 2015-16”.
There now seems little chance of any sort of market developing. Renal denervation has matched transcatheter heart valve implantation as one of the most exciting areas in interventional cardiology in recent years. Unlike transcatheter valves, it looks unlikely to fulfil its promise.
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