Ultimately, Boston Scientific decided in favor of partnering with Angiotech and entered into its novel alliance with Cook. For his part, Angiotech’s Hunter believes that Boston Scientific and Cook were ideal partners. Companies that trail the market leaders are typically more amenable to taking risks on new technologies.
“When you go to a market leader with a disruptive technology, most of the time they aren’t interested,” says Hunter. “If they already have a dominant position in a lucrative business, taking a risk on something that will cannibalize their own product is not something they’re likely to do. We talked to [the companies that trailed in market share], and those are the kinds of companies that will look up and say, ‘How can I get a piece of that pie?’”
Hunter notes that J&J was unusual in that it led the bare-metal-stent field and yet had a DES program. “They deserve a lot of credit for that,” he says. Angiotech has since signed deals with Broncus Technologies for the use of paclitaxel in an implanted device for emphysema patients and with CABG Medical for coronary artery grafts for use in bypass surgery. Companies interested in Angiotech’s expertise are “the ones trying to claw their way up. It’s not because we don’t want to work with the market leader,” says Hunter with a laugh. “It’s not like we have a predilection for the underdog.”
With their deal signed, Boston Scientific and Cook set to work on DESs. Cook made it to the market first, introducing the paclitaxel-coated V-Flex Plus PTX coronary stent in Europe in September 2002. However, after some disappointing clinical trial results and a failed merger with Guidant, the company withdrew from that market in 2004 to focus instead on making DESs for the femoral artery. “They were the first to launch a paclitaxel-coated coronary stent, and that was a big high…but ultimately they didn’t have the impact on cardiology that we had hoped,” says Hunter.
“It Felt Like a Vise”
It would be Boston Scientific, instead, that would have that impact. But creating the Taxus stent was not easy. A critical technical hurdle was the development of a coating for the stent that would release the paclitaxel slowly for about six months after surgery, after which the scarring response dampens. Angiotech had already tackled the problem, but Boston Scientific preferred to develop its own technology.
That left Angiotech on the sidelines as Boston Scientific methodically designed and developed its new stent. The biggest questions were about drug dosage and rate of release. Barry started with a large dose just to show that the drug-coated stent would indeed work in pig arteries. Satisfied that it had the desired effect, he performed a series of follow-up studies, each time halving the drug dose until he found a minimum effective dose.
The next step was to tinker with the polymer to find the optimum rate of release. Restenosis is essentially a case of the healing process getting carried away, with smooth-muscle cells migrating to the site of the injury with such exuberance that the artery is once again blocked. Paclitaxel inhibits that process, but Barry didn’t want to shut it down completely. He used trial and error to find a polymer with a drug release rate that would allow just enough cell migration to promote healing yet prevent it from going overboard.
Each study took three to six months to complete. Some of them could be done concurrently, but other studies had to be done consecutively, and the development dragged out. Hunter became anxious. He watched as J&J took over the lead in DES development. “At some point, I think we were even or a little ahead of J&J in terms of discovery,” Hunter recalls. But with every experiment Barry’s team performed, its chances of being first to market dwindled. J&J’s Cypher stent was approved in April 2003, and in October of that year, J&J published a study that reported impressive research results: Cypher had a restenosis rate of 5.9 percent, compared with 42.3 percent for bare-metal stents.