Edwards Lifesciences (EW) will spend Halloween casting frightened glances over its shoulder as it is pursued by a terrifying spectre: US approval of Medtronic's (MDT) CoreValve, which will destroy Edwards' monopoly of the catheter-delivered aortic valve space.
Data from the pivotal trial of CoreValve in patients who cannot undergo heart surgery was so positive that the FDA said it would not require an advisory panel to help guide its decision; approval in the first quarter of next year now looks all but assured. And with an overall survival rate of 76% at 12 months, compared with 69% in the pivotal trial of Edwards' Sapien valve, and a greater choice of delivery routes, Edwards has reason to be afraid.
The data, presented yesterday at the Transcatheter Cardiovascular Therapeutics (TCT) meeting, showed that in the 471 patients treated in CoreValve's US approval study, the rate of death or major stroke at one year - the primary endpoint - was 25.5%, much lower than the prespecified goal of 43%. The equivalent rate in the pivotal trial of Sapien was 35% (Event - CoreValve trial must give doctors a reason to switch, October 18, 2013).
Stroke is one of the main concerns with transcatheter valves, and CoreValve beat Sapien here too, with a rate of 4.1% at one year, compared with Sapien's 7.8% in its pivotal Partner trial. At 30 days, 11.5% of CoreValve-treated patients had more than mild valvular leakage; this improved to 4.1% at one year. More than 80% of patients with moderate leakage at one month had a reduction in the severity of leaking by one year. Medtronic claims that this improvement has not been reported in other major trials.
This last finding is particularly interesting in light of a separate review, also presented at TCT, of earlier study data, which showed that moderate or severe aortic regurgitation was seen in 16% of patients treated with CoreValve but just 9.1% of those implanted with Sapien.
The downside for Medtronic was the rate of pacemaker implantation - a pacemaker was required in 22.2% of patients. The rate with Sapien was around 6%. Medtronic was at pains to point out that pacemaker implantation was not associated with decreased survival at one year.
Comparing the results from two different trials is tricky and should of course be done with caution, but in the absence of a head-to-head trial it is hard to know how better cardiologists can judge the valves' performance.
Medtronic has already increased production of CoreValve in anticipation of US launch as soon as approval is granted. With the FDA making positive noises about approval in inoperable patients the process should be fairly straightforward.
The focus will then switch to gaining approval for use in patients who, while not totally unable to undergo surgery, are at high risk for complications. Pivotal one-year data in this cohort will be released at the ACC meeting in the spring, Medtronic says, with US approval occurring around a year from now. This time the FDA will be unlikely to waive the adcom.
The importance of the US market is growing, as the European market becomes more crowded. Boston Scientific's (BSX) Lotus aortic valve was CE marked on Monday, bringing the total number of transcatheter aortic valves on sale in Europe to seven.
Considering the excellent outcomes transcatheter valves can offer over surgery, uptake of the devices has been slower than expected. The devices can cost up to $30,000, far more than surgically-implanted valves, even taking the shorter healing times into account.
Their utility in inoperable patients is unarguable, but their cost-effectiveness in high-risk groups has been the subject of some discussion. Glenn Novarro, an analyst at RBC Capital Markets, says that both government and private insurers in the US strictly limited off-label use of transcatheter valves.
That said, in 2012, the US sales of Sapien totalled $238m and this will rise to $869m in 2018, according to EvaluateMedTech's consensus forecasts. CoreValve's US sales are predicted to grow faster, with $570m-worth of business expected in 2018. Cost-effectiveness is the name of the game, but there is still money to be made.