Drug-eluting stents (DESs) have become an indispensable technology for treating coronary artery disease since their introduction 12 years ago. The latest innovations, concerning ever thinner struts and the use of dissolving polymers to attach the drug to the stent backbone, are attracting interest, but entirely dissolving vascular scaffolds are now emerging as a force in the market. The battle is on to see whether these temporary scaffolds can displace new-generation metal-based DESs.
“Absorbable technology is not mature yet,” Carl Brakenhielm of Biotronik Vascular Interventions tells EP Vantage. “The scaffolds are far too bulky and they have other limitations – how much you can overexpand [them] and what size range is available. It’s more of a niche product.”
Biotronik is basking in the positive data from the 2,119-patient Bioscience trial of its Orsiro DES released at the meeting of the European Society of Cardiology last week and simultaneously published in the Lancet. Orsiro is a permanent metal stent with very thin struts, and an absorbable polymer. It was proven non-inferior to the current market leader and gold standard, Abbott Laboratories’ Xience Prime. Abbott’s stent is more standard in design, as this slide from the presentation shows.
Slide taken from presentation of the Bioscience trial results at the ESC meeting in Barcelona on September 1 2014, by Dr Thomas Pilgrim of the Swiss Cardiovascular Center, University Hospital, Bern, Switzerland.
At one year, target lesion failure – Bioscience’s primary endpoint – had occurred in 69 patients treated with Orsiro (6.5%) and 70 Xience Prime-treated patients (6.6%), giving a p value for non-inferiority of less than 0.0004.
Orsiro is already sold in Europe, but Mr Brakenhielm says that this new data ought to light a fire under the product’s sales.
“I think it will be excellent on a commercial level … it’s common that published data from randomised controlled trials with a clinical endpoint is requested. So I expect [the trial] to improve a chunk of the sales.”
He says that Orsiro had previously been seen as a device to treat the harder to reach stenosis in patients with tortuous vasculature, but as Bioscience has shown it to be as good as the best-in-class Xience Prime, the device could come to be more commonly used.
“When we had less data in the first years some doctors were hesitant to use Orsiro as their workhorse, but still they kept it on the shelf as a stent to use when it was really hard to treat the lesion. For everyday use they might still be using a competitor that had more documented clinical data. Now we have also qualified to be the workhorse, not just the one that you pick out for your special, more challenging cases.”
More compelling option
Such is the case for the defence. But for a newer technology to merely equal, rather than surpass, an older device is perhaps not so impressive, as Julinda Mehilli and Steffen Massberg from the Ludwig-Maximilians University in Munich, noted in an editorial accompanying the published Bioscience data in the Lancet. They suggest that future research could instead examine wholly bioresorbable vascular scaffolds – essentially dissolving stents.
Two such products have been granted European approval: Abbott’s Absorb and Elixir Medical’s DESolve (EP Vantage interview – CE mark for dissolving stent pits Elixir against Abbott, June 10,2013). Steve Kelly, a spokesperson for Abbott, tells EP Vantage that absorbable scaffolds have advantages over metal-based DESs, even those with temporary polymers.
“Absorb is fundamentally different than a drug eluting stent with a biodegradable polymer. As Absorb dissolves, the vessel has the potential to regain motion, flexing, pulsing and dilating in response to stress to the heart from normal activities such as exercise.
“Thus, a fully bioresorbable device that can demonstrate comparability to a metallic drug eluting stent, the standard of care, in a randomised trial would likely be a more compelling option for clinicians than a metallic stent with a bioresorbable polymer that still cages the vessel and remains in the body permanently,” Mr Kelly says.
Still, Absorb has been in Europe since 2011, and despite eluting the same drug as the market leading Xience franchise, has not taken over as the standard technology. Dissolving scaffolds are a huge technological change, but may never replace metal-based products.
“You would have thought a few years ago that the market would switch over to absorbable technology,” Mr Brakenhielm says. “Traditional permanent drug-eluting stents with only the polymer being absorbable are rather going to be the dominant factor in drug-eluting stents and drug-eluting scaffolds for many years to come.”
He points out that Boston Scientific, a major player in DESs, has switched to a dissolving polymer for its Synergy stent, and Biosensors International launched a similar device called BioMatrix Flex seven years ago. Both are available in Europe, but not yet in the US.
In fact, Biotronik is working on its own dissolving scaffold, which intriguingly is based on magnesium rather than the polylactide used by both Absorb and DESolve. A version using the same drug and release polymer as Orsiro is currently in first-in-human trials.
The battle will now shift across the Atlantic. FDA approval of Absorb is expected in the 2016 timeframe, and Mr Brakenhielm says that US launch of Orsiro could occur in a few years too.
“Orsiro has shown double digit growth each year since launch and is taking significant market share in all our key markets in Western Europe. It’s doing very well, it’s becoming a big share of our interventional business.”
Whether Orsiro can take on Absorb as well as the nine DESs already present in the US (see table below) is something only time will show. The Bioscience trial data is a start.
|Coronary drug-eluting stents in the US: first-time PMAs|
|Decision date||Company||Device name||Drug||Number|
|April 24, 2003||Cordis (Johnson & Johnson)||Cypher||Sirolimus||P020026|
|March 4, 2004||Boston Scientific||Taxus Express2||Paclitaxel||P030025|
|February 1, 2008||Medtronic||Endeavor||Zotarolimus||P060033|
|July 2, 2008||Abbott Laboratories||Xience and Promus||Everolimus||P070015|
|October 10, 2008||Boston Scientific||Taxus Liberté||Paclitaxel||P060008|
|April 22, 2011||Boston Scientific||Ion||Paclitaxel||P100023|
|November 1, 2011||Abbott Laboratories||Xience Prime/Xience Prime LL||Everolimus||P110019|
|November 22, 2011||Boston Scientific||Promus Element Plus||Everolimus||P110010|
|February 17, 2012||Medtronic||Resolute Microtrac/Resolute Integrity||Zotarolimus||P110013|
|Trial name||Trial ID|