When it comes to treating the narrowing arteries in the legs and thighs, Boston Sci has its Eluvia drug-eluting stent, which received a CE Mark in early 2016, and its Ranger drug-coated balloon, which received a CE Mark in 2014. (Until Boston Sci is able to market the Ranger in the U.S., the company is distributing C.R. Bard’s Lutonix drug-coated balloon.)
It goes without saying, though, that peripheral arteries are not the same as coronary arteries. Jeff Mirviss, the head of Boston Sci’s peripheral interventions business, recently explained the story behind the Eluvia and Ranger’s development to MDO:
MDO: What were some of the technological challenges that Boston Scientific had to overcome to create drug-eluting device technologies such as the Eluvia and the Ranger for use in peripheral vasculature?
Mirviss: Boston Scientific has been doing work in the drug-device combination in the vasculature for 2 decades. We’ve had a lot of success in coronary applications. A lot of our technology leverages the science and expertise and capabilities that we built over the years in this area. And while the coronary vessels are very different than the peripheral vessels in many ways, a lot of the base technology and the base science that we have was informative of our ability to make the devices work safely and effectively in the peripheral application.
To answer your question specifically with regard to challenges overcome, first is finding the right combination of drug and polymer or excipient [substance stabilizing the active ingredient], depending on which one you’re talking about – between drug-eluting stents and drug-coated balloons – that is safe but also effective. With some drugs, not enough drug, and you don’t get the efficacy. But too much drug might be problematic in terms of manufacturing or clinical safety. Finding the right therapeutic window has been definitely an area where that we’ve spent a lot of resources scientifically looking at the optimal combination of drug dose and polymer or excipient.
The second is with regard to having the drug stay on the device effectively within the coating but also coming off at the right timeframe. With our Eluvia drug-eluting stent what is unique about it is the drug is released over a 1 year period of time. That was by design because in the [superficial femoral artery] the restenosis [blood vessel narrowing] occurs over a bit of a longer period of time than the coronary arteries. Most restenosis in the coronary happens in about 6 months, but in the peripheral arteries it happens later, 9 or 12 months. Our hypothesis was that our drugs should be working when restenosis is most likely to occur. Getting the drug to release over the timeframe we wanted at the right rate was another technological challenge that took a lot of work to overcome.
MDO: How do you achieve that? How do you make that possible?
Mirviss: That’s where the polymer does its job. Unlike many other devices in which the drug is quite plainly put on top of the device, whereby the drug can come off during delivery of the device or putting the device through the introducer, the polymer and drug are put on top of the stent together in the manufacturing process. It’s a process to have the combination applied to the stent at the same time. And then when the stent is delivered, the drug can release over a given period of time. We can tune the release of the drug based on the rate the drug comes off as well as the length of time the drug comes off. You can make it come off very quickly in high amounts, or you can make it come off slower over longer periods of time. It’s a tunable technology we have. That’s what we believe is our secret sauce.
MDO: What is the difference when you go to peripheral? What do you have to keep in mind?
Mirviss: The first main difference is the underlying stent platform. In the coronary arteries, we use a balloon-expandable stent that’s very small and very short. In the peripheral arteries, we use a nitinol self-expanding stent that typically is much larger and much longer. So just the underlying medical device itself is very different. The size, the shape, the material, the length is very different. For example, a coronary might be 3 mm in diameter, while an artery in the [superficial femoral artery] might be twice that size. … The underlying technology is still a stent, but the way the stent is deployed is different. The size and length is different. You just think of the human anatomy. The arteries in the heart are very small; they’re not super long. But just think about the length of your entire thigh, and the size of the artery in the thigh is much bigger. The thigh has a lot more bending. … The anatomy is a lot different.
MDO: So what do you have to make sure doesn’t go wrong when you deploy something like that?
Mirviss: Stent technology has advanced quite a bit over the years. And one of the fundamental aspects of the Eluvia drug-eluting stent is that it builds off of our proven nitinol stent that we call Innova. It was studied in a trial of almost 300 patients. One of the hallmarks of it, other than its ease of use and deliverability for the physician, is that it is a very durable platform. The device itself is high performing. That was important because if the underlying stent platform isn’t very good, then it’s more difficult to have positive and longterm clinical results. One of the important aspects of Eluvia is it’s starting with a really good base platform of nitinol self-expanding stent.
The other big difference between coronaries and peripheral is the drug that’s used in the drug-eluting stent. In coronaries, the main drug that we use is called everolimus. It is in a class of drugs called olimus. In the periphery, at least in the SFA anyway, the primary drug that’s shown the best results is paclitaxel. The main technology for drug-eluting therapies between coronary and peripheral use totally different drugs.
MDO: Did that mean more rejiggering of the polymer drug mix because you had different chemicals you were working with?
Mirviss: Certainly, we have to do all of the required testing for a different drug. What we chose to do with the Eluvia was take the polymer from the coronary drug-eluting stent but then put it together with paclitaxel, because that’s the drug that’s been shown to be most effective and safe in the peripheral arteries. That did require a significant amount of work to validate that the drug comes off in the timeframe and quantities that we wanted to and a lot of preclinical tests and assay works and bench tests and manufacturing work. It was an easier project than starting from scratch, because we had really good understanding of the drug by itself and the polymer by itself. But then the combination of the two together required a whole new set of tests we hadn’t done before because it was new.
MDO: With the Ranger, Boston Sci has a paper online that describes how you went from coatings that were hydrophilic and moved to a coating called TransPax that is hydrophobic. So you’re turning to something new for controlled release?
Mirviss: In contrast to the Eluvia drug-eluting stent, the Ranger doesn’t have a polymer. The polymer allows you to control the amount of drug and the rate of the release, but you don’t have that with the balloon. So you have to figure out a way to make the drug stick to the balloon so that it stays on it long enough to get where you want it to go and work in the artery. If it comes off, the drug can’t do its job if it’s not in the right location or right amount. So in partnership with an external company [undisclosed] that had some really good capabilities in coatings, we came up with a really good proprietary coating called TransPax that allows the drug to adhere to the balloon very effectively with extremely low particulates, which is a really important design aspect. You don’t want the coating to come off during the delivery and flow downstream. When you inflate the balloon, you want the drug and the coating to adhere to the side of the vessel wall so that the drug can do its job where you want it to be. So that was the biggest hurdle with the drug-coated balloon.
MDO: So it was a partnership with a supplier to make the Ranger balloon possible?
Mirviss: We call this a co-development project, because what we bring to the table is that we have really good balloon expertise going back 35 years, and then we bring the drug expertise because we’ve been doing drug-device combinations for 20 years and have a market-leading position in coronary drug-eluting stents. We had these great capabilities with balloons and drugs, but we didn’t have the technology we needed with coatings. So we entered into this arrangement to bring an expert to the table who really understood coatings. So it was a really good partnership and really good project.
MDO: Any lessons from the partnership that would be good to others entering into a partnership with suppliers?
Mirviss: Begin with the end in mind – to the extent that both parties can have clarity to what the future holds and the different scenarios for the future so that nobody is surprised or has different expectations. I think we were very aligned from the beginning in what our capabilities were and what both of us wanted. That worked extremely well. We also had very clear milestones so both companies could work together and achieve those milestones in a way that has quality but also speed. We laid those out in advance so that everybody could agree to it. It was a key success factor. And then just like with anything else, it was the relationships within the team. Getting the right people with the right knowledge and building the right relationships helped us have a constructive partnership because there was trust.
MDO: So what’s next? Where would you like to see drug-eluting technology go in the future?
Mirviss: As we look at different disease states, we ask ourselves, ‘Where does it make sense to leverage a technology like we have in drug-eluting stents and drug-coated balloons to other disease states beyond the typical peripheral type vessels?’
The second area could be the disease states we already sell products into, and you look at the range of complexity of the disease. We’re starting to ask, ‘Are there more complex patients and lesions whereby we could modify the drug or the device or the combination to treat more complex patients and lesions?’ It’s not dissimilar to how in the pharma world they might have a product and then a higher dose of a product or a sustained release or some other slight modification that might be more effective for a different patient within that same disease state.
MDO: When does it make sense to build off existing technology, and when does it make sense to do something that’s truly novel?
Mirviss: We definitely have some investments in new-to-the-world technologies and exploratory research and areas where we think we could bring medical device innovation to advance the care of patients in ways we don’t know about today. Right along with that, we look at, ’Where do we have capabilities? Where do we have technologies? How could we leverage what we know into new uses or with new users to help advance the care of patients and bring a cost-effective solution to healthcare?’ I really believe medical technology can be a solution to lowering the cost of healthcare. Being able to take our core technology in our coronary drug-eluting stents and applying it to peripheral was faster and less expensive and allows us to get to the market faster than a company that would have to start from scratch.
If we’re successful in this endeavor, we will allow patients to be treated with this state-of-the-art technology that will lower the incidence of a repeat procedure. That’s not only good for the patient, because they don’t have to have a second surgery, but that’s good for the healthcare system because it’s lower cost.
[Want to stay more on top of MDO content? Subscribe to our weekly e-newsletter.]