Polymer-based bioabsorbable stents are expected to grab significant market share from bare-metal and drug-eluting stents, reaching a value of more than US$1.7 billion by 2017, according to a recent report published by Global Data. Companies such as Abbott Vascular, Boston Scientific, Elixir Medical, ICON Interventional, Medtronic and REVA Medical are currently conducting research and clinical trials with the aim of commercialising their bioabsorbable stents. One of the pioneers of this technology, Kyoto Medical Planning Co. (Kyoto, Japan) successfully obtained the CE mark in 2007 for its bioabsorbable peripheral stents, which are sold in 11 European countries and Turkey. Keiji Igaki, co-developer of the innovative stents and President of Kyoto Medical Planning, told Japan Medical Design & Manufacturing Technology how he and the late Hideo Tamai, a cardiologist, developed this breakthrough device.
JMD&MT: How did you two come up with the idea of bioabsorbable stents?
|Keiji Igaki, President of Kyoto Medical Planning|
Igaki: The idea was originally introduced by a team led by Dr. Richard Stack at Duke University in 1990. The concept of bioabsorbable stents was brilliant; however, commercialising them was extremely difficult for the team. Dr. Tamai (Assistant Director of Shiga Medical Center for Adults in Japan at that time) was inspired by Dr. Stack’s idea, and enthusiastically knocked on my door, asking if we could make absorbable stents in Japan together.
JMD&MT: You initially believed that PLLA was an unsuitable material for bioabsorbable stents. Why?
Igaki: Well, bioabsorption is not the only job for bioabsorbable stents. They have to scaffold the narrowed site in the vessel for roughly six months to maintain blood flow, and the PLLA stents seemed to be inferior in strength for this task.
Initially, we selected PGA as the base material for our stent following advice from polymer specialists at the Kyoto Institute of Technology. But repeated implantation tests in dogs and pigs using PGA stents didn’t show good results.
PGA’s degradation rate was so high that stents made from this material could not hold open the vessel for the required period of time, which resulted in repeated narrowing of the vessel. After consulting with specialists at the institute again, we decided to take the thorny path and try PLLA. This was indeed a daunting challenge!
However, we did succeed in developing a bioabsorbable stent that is both biocompatible and sufficiently strong by controlling molecular weight.
JMD&MT: How long does it take for the PLLA stents to be completely absorbed into the body?
Igaki: Our Igaki-Tamai stents for peripheral artery, named Remedy, can maintain their radial force for roughly six months. They are metabolised into water and carbon dioxide in the presence of fluid in the blood and completely absorbed in the body within one to two years after implantation. There are no safety concerns involving PLLA, because lactic acid is a substance that is originally present in the human body.
JMD&MT: Please describe your stents.
Igaki: Struts of 0.17 mm diameter are meshed into a tubular structure to make the stent. We took advantage of our internal technology of making ultrathin polymer tubes. In Europe, we are currently selling eight types: 3.6 and 7.8 cm long stents in diameters measuring 5, 6, 7 and 8 mm.
The stent is expanded by means of a balloon, which is inflated by contrast media. At an earlier stage, specialised thermal contrast media was required to expand the balloon, but expansion can now be achieved using room-temperature contrast media.
JMD&MT: Compared with metallic stents, it seems that the bioabsorbable PLLA stents can be used in broader applications.
Igaki: Exactly! It is possible to use them in patients who have metal allergies or who are still growing. Even if the stented segment narrows again, the implanted PLLA stent will not interfere with other procedures, such as restenting.
PLLA stents are more useful as drug-delivery platforms than metal stents because PLLA dissolves at a much lower temperature and can be coated more easily with a polymer-containing drug than metal.
JMD&MT: The Igaki-Tamai stent for peripheral artery has carried the CE mark since 2007. It is the first commercial stent in the world with bioabsorbable technology, isn’t it?
Igaki: Obtaining the CE mark is not so difficult, as the CE mark requires meeting a minimum set of standards to place products on the market. In Europe, manufacturers like us take full responsibility for a defective product. In other words, it is easy to start selling but you have infinite liability. Therefore, we spent more than a year to further improve our product before launching it in the European market in 2009.
Regarding PMDA approval in Japan, we have just started the application procedures, but PMDA’s standard is rather stringent. I hope that I can bring you good news by next year.
JMD&MT: How about your plan for the US market?
Igaki: We have no plans to obtain FDA approval and sell our products in the United States, because there are a lot of huge medical device companies and we don’t want to be like Gulliver in Brobdingnag, the land of the giant men.
JMD&MT: When do you think you will be able to sell your stents in Japan?
Igaki: Luckily, we received a grant in October 2011 from the Ministry of Economy, Trade and Industry for a programme “to support collaboration between hospitals and businesses for the development and improvement of medical equipment and devices to solve unmet medical needs.”
Under this three-year supporting programme, we are doing research with the Kyoto Institute of Technology to enhance the strength of the PLLA stents in the first year. In the second year, we will perform clinical trials at Keio University, and in year three (2014), we will go through the PMDA approval process to start marketing the highly improved stents in Japan.
While the grant is aimed at marketing our peripheral stent, we’ve already developed coronary stents and started clinical trials at institutes in Germany. To my deepest sorrow, Dr. Tamai passed away in 2009. However, the Igaki-Tamai stents, I believe, will continue to expand their presence in the world stent market.
Kyoto Medical Planning currently has 60 employees, seven of whom are in charge of development of the stents. The stents are manufactured at their ISO 13485–certified facility. The company has a sales office in Munich, Germany.
Miki Anzai is Associate Editor of JMD&MT.