The advent of drug-coated stents changed the interventional cardiology landscape. Some companies are hoping to repeat the trick, betting that the next big advance will be the elimination of the polymer coating used to affix the drug to the stent’s metal frame – and the bet has largely looked like a safe one.
The failure of Terumo’s (OTC:TRUMF) drug-eluting stent Nobori, which uses a biodegradable polymer, to prove non-inferiority to Johnson & Johnson’s Cypher in a late-stage clinical trial is therefore something of an anomaly. And while this is a blow to the Japanese company, it will perhaps come as a shock to Singapore’s Biosensors International, which signed a deal yesterday to co-promote the device in Japan.
Stents with dissolving polymers have been developed as a response to data linking polymers to adverse events such as late thrombosis. The first entirely polymer-free drug-eluting stent (DES) to reach the U.S. was Cook’s (OTCPK:TCKGY) Zilver PTX in November (Cook has U.S. peripheral drug-eluting stent market on a Zilver platter, November 16, 2012). But this is used in the peripheral vasculature; the real dogfight is in the coronary setting.
No wholly polymer-free coronary DESs have yet reached the U.S., though Biosensors’ (OTC:BSNRF) rival device BioMatrix Flex, which elutes the firm’s proprietary drug biolimus A9 using a dissolving polymer, is available in Europe. Both BioMatrix Flex and Nobori are CE marked.
Nobori came unstuck in the 1,229-patient Sort Out V trial, which tested it against the sirolimus-eluting Cypher Select Plus, which has a permanent polymer and was developed by Cordis, a subsidiary of J&J (JNJ). The Cypher product line, the first of which was the first DES to be approved in both Europe and the U.S., has long been regarded as the gold standard for safety. However, in terms of efficacy it has been eclipsed in recent years by newer devices, particularly Abbott Laboratories' (ABT) everolimus-eluting Xience V, now the U.S. market leader.
In the intent-to-treat population of Sort Out V, the rate of cardiac death, heart attack, definite stent thrombosis or target vessel revascularisation – the primary endpoint – was 4.1% for Nobori and 3.1% for Cypher. At p=0.22 the difference was not significant, and Nobori also failed to meet a prespecified standard for non-inferiority, yielding a p value of 0.06.
Worryingly, the main difference seemed to be in the thrombosis component of the endpoint, precisely the defect the removal of the polymer is intended to address. Definite stent thrombosis rates were 0.7% for Nobori and 0.2% for Cypher at both nine and 12 months.
This is galling for Terumo given that in a similar trial, Leaders, BioMatrix Flex showed convincingly positive results compared with Cypher Select. Biosensors, which decided to co-promote Nobori despite having a safe, effective dissolving-polymer DES of its own, might be even more disappointed.