Drug-eluting Stents Part Two Triple Storm Catching Industry Attention

Thinking about Life Sciences: Drug-Eluting Stents, Part Two: Triple Stor...

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Thinking about Life Sciences http://blog.aesisgroup.com Tuesday, November 28, 2006 Drug-Eluting Stents, Part Two: Triple Storm Catching Industry Attention

According to most business logic, market share can be won on the basis of product differentiation and/or lower cost. Product differentiation as the driver is perhaps too broadly construed to capture the important differences between incremental and disruptive technology improvement. As discussed on Monday, the Conor stent is an example of an incremental improvement. Leapfrogging Technologies It has always been my view that drug-eluting stent (DES) technology is essentially a “transitional” technology (to some extent, all technologies are) and that it will be replaced (leapfrogged) by other technologies. I believe that this inevitability is closer to us than many would think or hope. The New England Journal of Medicine on Nov. 16 featured an article headlined “Treatment of Coronary In-Stent Restenosis With a Paclitaxel-Coated Balloon Catheter” along with an accompanying editorial. This article represents an interesting approach to the problem in which the anti-restenosis agent is used only in the very short term and layered on the balloon rather than associated with the stent and any carrier polymer. The success of all this depends upon a rather careful kinetic dance coordinating the duration in which the balloon-covered drug sticks around the artery wall, the time period to achieve full healing of the vascular wall endothelium and the time period over which the scarring process (e.g. restenosis) occurs. Since the factors influencing such kinetics include so many diverse elements, it is not possible for a single device or even a palette of devices to be designed that get it right. Every patient (and each artery with its unique anatomy) will require a different device with different drug loading and kinetic parameters. In my estimation, it’s not just not possible. The Abbott Strategy Another important development can be found in the recent announcement from Abbott Laboratories reporting initial clinical trial results from its fully “bioabsorbable” drug-eluting coronary stent, which was also just presented at the October TCT conference in Washington, D.C. The idea is that the restenosis-inhibiting stent actually dissolves over time within the vessel lumen and presumably leaves behind a fully open and healed coronary artery. On the surface, this seems like an extremely promising approach. In arguing for the benefits of a temporary - bioabsorbable or “meltaway” stent, Dr. John Ormiston (a cardiologist and principal co-investigator on the project) recently said in the New Zealand Herald: What we have now (with current DES) is a permanent implant for a temporary problem. … If you look at a cast on your arm, there’s no point keeping it on your arm for the rest of your life. However, there is a problem with this logic. It is usually through an accident - unlikely to happen again that one has the misfortune of breaking an arm. Along with the fact that healed bone is often stronger than it was originally, this means that wearing a cast indefinitely makes no sense. However, let’s say, for example, that while skateboarding you broke your elbow. As a professional

11/17/2008 12:50 AM

Thinking about Life Sciences: Drug-Eluting Stents, Part Two: Triple Stor...

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skateboarder, the risk of breaking your elbow again is very high. While you wouldn’t wear a cast for the next time around, even the wildest skateboarders wear ample elbow protection. By analogy, there’s a reason why a clot (or blockage) occurred at the particular segment of the affected artery. There is something about the anatomy and/or the turbulent flow dynamics – coupled with the patient’s own physiology and lifestyle – that made that particular section susceptible to being blocked (thrombosed is the technical term). A coronary lesion is hence just like a skateboarder who does have a susceptibility to breaking elbows and other such body parts. For both the coronary lesion and its metaphor - the skateboarder, providing only a transient, temporary fix does not solve the problem. One can even argue that a segment already prone to thrombosis and/or blockage could be rendered even more dangerous by the distortions introduced by the temporary angioplasty and stenting procedure. The other reason why the broken bone analogy fails is that setting a cast on a patient involves very little risk and cost. The same cannot be said for an interventional procedure in which a patient is placed under anesthesia, the femoral artery accessed, a catheter threaded up to the heart and an artery-opening procedure performed. It would seem that by using a bioabsorbable stent, the reward of providing only temporary fix to a serious, essentially recurrent problem will never match the accompanying risk. Though we are entering an interesting era in which minimally invasive techniques so substantially reduce the risk of intervention that even temporary rather than definitive measures can be even considered, I don’t think this will apply in the case of coronary artery disease. Where Does That Leave Us? Given the above, we have a potential situation in which: 1. the FDA mandates stricter controls over DES usage, 2. Johnson & Johnson goes the route of incremental technical improvement without necessarily solving the DES problem, and 3. Abbott Laboratories takes a brave but potentially dead-end approach. That leaves Boston Scientific. What are they up to? What should they do? One recommendation would be for them to pursue a radically innovative approach that keeps the stent (e.g. permanent fix) but gets rid of the anti-proliferative agents and the polymer resulting in long-term in-stent thrombosis. Ogan Gurel, MD MPhil [email protected] http://blog.aesisgroup.com/ Boston Scientific Drug-eluting stents Abbott Laboratories Johnson and Johnson device safety in-stent thrombosis Aesis Research Group Ogan Gurel MD

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