Anyone worried that Boston Scientific had bought Symetis as a hedge against failure of its in-house transcatheter aortic valve, Lotus, today finds their scepticism misplaced. Lotus has beaten Medtronic’s CoreValve in a rare head-to-head trial of these devices, and chances of US approval now look good.
That is, once Boston has sorted the manufacturing issues that led to Lotus being recalled from sale in Europe in February. And if the valve is rubber-stamped by the FDA, there is another fight ahead: the market leader is Edwards Lifesciences’ Sapien franchise, and even a clear win against CoreValve will not allow Boston to displace it.
Instead Boston will be looking at the second-largest share of the market for transcatheter aortic valve implantation (TAVI) products – at best. Lotus will not be back on sale in Europe until the fourth quarter of this year, and its US launch – assuming the FDA nods it through – will not happen for the best part of a year. In the meantime Edwards and Medtronic will entrench their current positions further, and Boston will have to fight that much harder.
Still, the data from the Reprise III study do show a clear advantage for Lotus over CoreValve. The trial signed up 912 patients from the US, Europe, Canada and Australia with severe aortic stenosis who were at high or extreme risk of complications were they to undergo surgical valve replacement. Boston’s valve showed non-inferiority to CoreValve for the primary safety endpoint, a composite of death, stroke, bleeding, acute kidney injury or vascular complications at 30 days.
More impressively, it nailed superiority on the primary efficacy measure, a composite of death, disabling stroke and moderate or greater paravalvular leakage at one year. These events were seen in 16.7% of the patients treated with Lotus versus 29% of those given CoreValve (p<0.001).
Leakage is an important metric when doctors are considering which valves to use. It was broken out as a prespecified secondary endpoint, and again here Boston’s device beat the competition: Lotus-treated patients had significantly lower rates of moderate to severe paravalvular leakage occurrences compared with CoreValve, at 2.0% versus 11.1% (p<0.001).
Stroke rates are also crucial; there was no significant difference between the valves on overall strokes at either 30 days or one year, but Lotus was significantly better on disabling strokes at the one-year point.
There were downsides. Lotus was associated with significantly higher rates of pacemaker implantation – 29.1% of Lotus patients were given a pacemaker by the 30-day mark, compared with 15.8% of CoreValve patients. The next-generation Lotus Edge includes a feature called Depth Guard designed to combat this.
So far, so good. But many of the devices used in Reprise III will not be used in the real world. The initial iterations of CoreValve and Lotus have been superseded, CoreValve by CoreValve Evolut R and Evolut Pro, and Lotus by the Lotus Edge – already CE marked and the version for which Boston intends to seek US approval later this year. Some Lotus Edge devices were used in the trial, but only in two of the seven study arms. The older Lotus was used in four arms.
Still, a hit is a hit – and a hit on both primary endpoints in a pivotal trial likely means approval. After the Lotus recall Boston said it would be able to launch the Lotus Edge in the US in the middle of next year (No Lotus élan for Boston, February 24, 2017). The data will not allow Lotus to knock Edwards’ Sapien from its perch as the bestselling TAVI product range. Frankly it is hard to imagine anything that could – there is a reason, after all, that Boston chose CoreValve rather than Sapien as the comparator.
But the Reprise III results ought to make Lotus more competitive with CoreValve in the race to second place. A head-to-head trial is always a risk, but sometimes it pays off.