Eight months after failing to establish non-inferiority to a first-generation drug-eluting stent (DES), Terumo’s Nobori DES has managed to succeed against a newer device. In a head-to-head trial with Medtronic’s Resolute Integrity, the rates of major adverse events at 12 months were near-identical.
Still, the new trial, Sort Out VI, is a disappointment. Nobori is one of a growing number of stents in which the polymer used to attach the drug – in Nobori’s case biolimus – to its metal struts dissolves over time, in an attempt to reduce thrombosis and subsequent complications. By rights, the stent should have resulted in fewer events than Resolute.
In Sort Out VI 1,502 patients were treated with Medtronic’s device and 1,497 with Nobori. A year after implantation the composite rate of cardiac death, heart attack and target lesion revascularisation was 5.3% in patients treated with the zotarolimus-eluting Resolute Integrity and 5.1% among those who received Nobori, giving a p value of 0.006 for non-inferiority, the trial’s primary goal.
Naturally this result is better for Terumo than the data from the failed Sort Out V trial, in which Nobori was outmatched by Johnson & Johnson’s Cypher stent (Failure of Nobori trial raises questions for dissolving-polymer stent rivals, February 8, 2013). But it looks as if Nobori’s biodegradable polymer might not make much of a difference to the stent’s performance.
The trouble faced by Terumo and other companies developing innovative stents is that the DESs already on the market are highly effective. In fact, the Resolute devices are a relatively easy mark; Abbott’s Xience product line, also marketed by Boston Scientific under the Promus brand, is the market leader thanks to its superior performance.
Speaking at TCT, Gregg Stone of Columbia University in New York said that the best way to obtain evidence of an advantage with Nobori and similar devices might be to test them in high-risk subgroups. It will also be interesting to see longer term data. The polymer is designed to dissolve within nine months of stent implantation – perhaps a difference favouring Nobori may yet emerge from Sort Out VI.
The other question hanging over the newer types of DESs, including those that use dissolving polymers and those made wholly of polymer that dissolve entirely, is one of cost-effectiveness. Both Abbott and Californian firm Elixir Medical sell drug-eluting bioresorbable scaffold devices in Europe, and Abbott’s costs around $3,600 – up to four times as much as a standard metal DES (Therapeutic focus – Bioresorbable stents are here to stay, June 10, 2013).
The dissolving devices have advantages; they allow the blood vessel to regain the same flexibility and contractility it had before implantation and, unlike metal DESs, they do not debar a recipient from heart bypass surgery. But they tend to have thicker struts than standard DESs, making them tricky to deliver, and cannot address complex lesions as well as metal DESs.
Abbott is planning two studies, Absorb III and Absorb IV, to compare the Absorb scaffold with Xience in a total of around 5,000 patients with the aim of showing differences in target lesion failure and angina at 12 months. Absorb III is expected to complete enrolment by the end of 2013 and Absorb IV is due to start next year.
If Nobori is non-inferior to Resolute Integrity, that could well be enough to secure it US approval. But if it cannot demonstrate better outcomes than its forerunners Terumo will not be able to price it at a premium. If it has no clear clinical advantage, it has no commercial advantage either.
|Trial name||Trial ID|
|Sort Out V||NCT01254981|
|Sort Out VI||NCT01956448|