Summer is behind us, but clearly it was sizzling with respect to the field of interventional cardiology, especially with the dramatic announcement from Cordis/Johnson & Johnson on the production cessation of the Cypher sirolimus-eluting stent (SES) by the end of 2011 and the abandonment of the development plans for the NEVO SES.

The announcement, which stunned the interventional cardiology community, may reflect the end of an era regarding the drug-eluting stent (DES) field and warrants a few editorial comments.

The Cypher SES is considered an icon in the DES field; it was the first-ever DES to reduce restenosis when compared to bare metal stents. The manufacturer’s rationale for ceasing production of the Cypher stent and abandoning the NEVO program was reported as such: “Targeted dynamics in the DES market that have changed considerably in recent years and continue to evolve in areas such as demand, pricing and reimbursement, and regulatory requirements for breakthrough new technologies. Unlicensed competition from products that infringe Cordis patents, owned and licensed, has eroded CYPHER Stent pricing, sales and market share, and has dampened the prospects for NEVO Stent commercialization.”

Indeed, over the past few years, DESs have become a commodity that reflects maturity in a field that began more than a decade ago. For the last decade, fierce competition has led to the development of second-generation stents, which primarily improved the deliverability of the stent when compared to Cypher and perhaps improved the safety with regard to a more compatible polymer. Ironically, when compared to Cypher, even the best second-generation DESs failed to beat Cypher’s efficacy in comparative observational registries and in randomized clinical trials.

Since the 2003 approval of the Cypher stent for marketing in the US by the FDA, we in the US have not seen any iterations or improvements made to the device. In 2011, Cypher is considered ‘old’ technology by being a first-generation DES with a polymer reportedly associated with adverse events in regard to biocompatibility. Meanwhile, second-generation DESs were launched, which resulted in changes in market share at Cypher’s expense. The competition resulted in price erosion, which is not all that surprising; naturally, after 8 years on the market, the price was likely to come down. If the industry wants to maintain high pricing and profit margins, it must continually iterate and improve the product.

The question remains as to why Cypher did not follow suit. Did the manufacturer lack the know-how or simply believe that the stent was optimal for its intended use? Did they believe that there was no need for further improvement or was it the regulatory hurdles (and associated excessive costs) one has to jump even for making minor changes? In the case of Cypher, there was a more deliverable version approved in Europe that was never marketed for approval in the US.

We heard that the nonofficial reason was that it would have cost too much to seek an approval for an improved version of the Cypher stent, and, instead, resources would be targeted to develop a dedicated third-generation DES with a biodegradable polymer (the NEVO program). Indeed, the costs to develop a new DES program in the US have escalated significantly over the past decade; in 2001, it was around $100 million. It is estimated that the cost to bring the NEVO program to the US market would exceed $500 million; and without reimbursement matching, it would be difficult to justify.

The regulatory scrutiny, especially with the late stent thrombosis issues seen with first-generation DESs, has only prolonged the gap between device approval outside of the US to that within the US, which also discourages the industry to launch new DES programs in the US. When the DES was launched in 2003, the reimbursement rate was nearly double that of bare metal stents. If the industry is not rewarded (a reward based on improvements in product performance) for a new and better product, we may see a freeze in the development of new DESs. The computer industry has taught us that, in order to survive in the marketplace, you need continual iterations and improvements of the product, costs of production must be reduced, while research and development budgets must increase despite modest erosion in revenue.

With DESs, efficiency must improve in production, regulatory processes, and clinical trial design, etc. For the past few years, we have experienced a decline in DES programs developed for approval in the US. The reason is multifactorial. In addition to the regulatory requirements and the erosion in reimbursement, the industry is targeting emerging markets in China, India, and South America. Perhaps we should admit that it is quite difficult to further improve the second-generation stents and that resources may be better spent elsewhere.

Outside of the US, we see continued development of what is to be considered third-generation DESs with bioabsorbable polymers or polymer-free DESs along with fourth-generation DESs with a completely biodegradable stent. The NEVO stent was supposed to be the first DES with a biodegradable polymer to be tested in the US. The manufacturer’s decision to abandon the program is disappointing. If the decision was related to the properties of the NEVO stent, it would be understandable; however, if a manufacturer with the necessary resources chooses to cease development of newer-generation DES in the US for commercial reasons, the future of US device development and accessibility to new technology is unclear. Hopefully, other manufacturers with access to novel stent technology for second- and third-generation DESs will take a different approach and consider the US market, will prove that there is still a merit in DES technology for our patients.

In the cases of Cypher and NEVO, perhaps the winners are the manufacturer and its competitors. The manufacturer is able to cut its losses and target resources toward the development of other technologies, while its competitors could possibly gain market share due to the disappearance of what used to be the DES leader. In my opinion, however, there are no real winners. Unfortunately, the main losers in this scenario are the interventional cardiologists and their patients who may miss out on the opportunity to be treated with improved DES technology. Hence, it is vital that industry leaders, physicians, and regulatory officers meet to discuss the best ways to facilitate further improvements and optimization of DES technology.