It is well known that it is much easier to gain European approval for a medical device than it is to obtain a US FDA green light. Sometimes the European market can bristle with competing devices before a single one has made it to the US.
Such is the case with drug-eluting balloons (DEBs). None has yet been approved in the US, but the European market is already crowded, with the first gaining CE mark in 2007. Now the technology is finally moving towards the world’s biggest market, with Medtronic submitting the first approval application to the FDA. However, the lag between Europe and the US could mean that when these devices do cross the Atlantic, they may find their niche already occupied by newer technology.
Functioning like a more transient version of drug-eluting stents, DEBs open up constricted arteries and deliver a brief burst of an antiproliferative drug when they touch the epithelium. Unlike most drug-eluting stents, however, they largely do not treat the coronary arteries, instead treating lesions in the peripheral vasculature such as the superficial femoral artery. The endgame here is preventing complications including leg ischaemia and deep-vein thrombosis, which can lead to leg amputation and death.
So far, all the balloons to reach the market have employed the same drug to guard against the vessel re-narrowing: paclitaxel.
Used on Boston Scientific’s Taxus drug-eluting coronary stent, paclitaxel has been largely superseded as a stent coating by the more effective 'limus mTOR inhibitors – sirolimus, everolimus and novolimus. Boston has since stopped selling Taxus. The reason the mTOR inhibitors have not made the leap to DEBs is that, unlike paclitaxel, they are not absorbed quickly enough by the vessel wall.
DEBs will have a fairly clear shot at the US market. Only one drug-eluting stent, Cook Medical’s Zilver PTX, has made it that far in the peripheral arena. Even better for the competition, the device has since been recalled owing to problems when it detaches from its delivery device (Zilver tarnished as FDA says recalled stent could be lethal, May 29, 2013). Interestingly, Zilver PTX also elutes paclitaxel rather than one of the more effective 'limus compounds, despite its durable nature.
The leading DEB, Medtronic’s IN.PACT Admiral, is slated for US approval for peripheral artery disease in 2015. Zilver PTX probably will have returned to the market by then, but the recall may have sown seeds of doubt for the technology among doctors – something from which DEB makers can profit, as the detachment problem does not apply to balloons.
Not all DEBs are intended solely for the peripheral arteries, though, and in the coronary space they face another, more specific competition. The main advantage balloons offer over stents is that they allow cardiologists to treat diseased arteries without having to leave a permanent implant behind. But there is another technology with the same USP: bioresorbable drug-eluting stents (Bioresorbable stents are here to stay, June 10, 2013).
There are fewer of these on sale in Europe – just two so far – but the most-advanced dissolving stent, Abbott’s Absorb, will see its pivotal US trial read out in 2015, with a filing and approval likely to follow in short order. IN.PACT Admiral is set to be the first coronary balloon too, so the race to the US could be neck-and-neck.
Coronary DEBs need not always compete with stents, however: in some cases they can be used in combination with them. Opto Circuits’ Dior balloon, for example, is used to deliver the same company’s Magical drug-eluting stent, thereby providing an extra boost of an antiproliferative drug. DEBs can also have utility in in-stent restenosis, where an artery re-narrows, collapsing the stent already implanted in it.
The so-called “device lag” – the delay between EU and US approval – is notorious, all the more so since no similar situation exists in the regulation of drugs. The lag averages around three to five years – Zilver PTX, for example, saw a three year delay – but with drug-eluting balloons it will be at least eight.
Analysts at Goldman Sachs say that by 2017, Medtronic and CR Bard will hold leadership positions in drug-coated balloons, with 39% each of the worldwide market, which will then be worth $500m. This is small potatoes compared to the drug-eluting stent market, which already clocks in at $4.5bn and is still growing.
By 2021, Medtronic and CR Bard will hold market share of 33% and 36%, respectively, with Covidien comprising 16% of the market and other players making up the remaining 26%, Goldman Sachs say.
In the peripheral arena DEBs could do well, but in coronary artery disease the products may struggle to distinguish themselves from newer technologies.
|Selected drug-eluting balloons|
|Device||Company||Peripheral or coronary||EU status||EU approval (CE Mark)||US pivotal trial (IDE) initiated||Strategy|
|Dior||Opto Circuits||Coronary||Marketed||15/02/2007||-||Company acquisition (Eurocor)|
|SeQuent Please||B. Braun Melsungen||Coronary||Marketed||30/03/2009||-||Organic|
|IN.PACT Admiral||Medtronic||Coronary and Peripheral||Marketed||19/05/2009||15/10/2010||Company acquisition (Invatec)|
|Freeway 014||Opto Circuits||Peripheral||Marketed||22/11/2010||-||Company acquisition (Eurocor)|
|Lutonix||C. R. Bard||Coronary and Peripheral||Marketed||28/06/2011||25/07/2012||Company acquisition (Lutonix)|
|Freeway 035||Opto Circuits||Peripheral||Marketed||-||-||Company acquisition (Eurocor)|
|Lutonix 014||C. R. Bard||Peripheral||R&D||-||04/06/2013||Organic|
|IN.PACT Amphirion||Medtronic||Peripheral||R&D||-||-||Company acquisition (Invatec)|
|Drug Coated Balloon platform||Covidien||Peripheral||R&D||-||-||Company acquisition (CV Ingenuity)|
All data sourced to EvaluateMedTech