Peripheral arterial disease (PAD) affects around 8–12 million people in the US.[1] The strong association with ageing, tobacco smoking, and diabetes means that the prevalence of PAD will continue to increase in the coming years. Although 20–50% of patients with PAD are asymptomatic, they are still at significant risk of adverse outcomes due to the co-prevalence of coronary, renovascular and cerebrovascular diseases. Five-year mortality approaches 30% in the population and five-year lower extremity amputation risk is 2–5 % or higher in particular patient subsets, such as those with diabetes or who are smokers.2 Most of the PAD lesions are located in the femoropopliteal arteries.
The Eluvia drug-eluting vascular stent system is a self-expanding metal (nitinol) stent intended to treat PAD. It was developed by Boston Scientific as the counterpart of Zilver PTX from Cook Medical for femoropopliteal lesions treatment. The Eluvia stent first obtained the CE Mark approval in February 2016, which allowed the company to distribute the product in the European market. To seek approval in the US market, the company submitted a pre-market approval (PMA) and obtained FDA approval for the Eluvia stent system in September 2018.[2]
The CE Mark approval was primarily based on data from the MAJESTIC trial, a head-to-head study comparing the clinical performance of Eluvia and Zilver PTX in femoropopliteal lesions. This prospective, single arm, multicenter trial assessed the safety and performance of the Eluvia stent system and reflected a primary patency rate of more than 96% (57 patients were involved). Although MAJESTIC was considered as a small trial, it showed the highest patency rate reported among prior drug-eluting system (DES) trials.[3]
To generate the clinical data in support of the PMA for the FDA submission, a global, prospective, multicenter IMPERIAL clinical trial was initiated in early 2016. The study compared the safety and effectiveness of the Eluvia DES versus Zilver PTX for the superficial femoral or proximal popliteal artery lesions up to 140mm in length. It randomised 309 patients with occlusive lesions of the superficial femoral or proximal popliteal arteries to the polymer-coated, paclitaxel-eluting Eluvia stent and 156 to paclitaxel-eluting Zilver PTX, which is the only drugreleasing stent approved in the US for the indication.[4]
There are several factors that influence the length of time it takes for a medical device to reach its end user in a specific jurisdiction. Companies that manufacture medical devices frequently face a challenging decision whether they should try to bring their products to the European or US market first. From a timeline perspective, there used to be a delay in launching new medical devices in the US compared with Europe. This was partly due to the fact that, before the new medical device regulation in Europe, the European regulatory process used to be less bureaucratic and more predictable than the one in the US.
For a class III device such as the Eluvia drug-eluting vascular stent system, the timeline for obtaining a CE Mark was typically much shorter than the one for obtaining FDA approval of a PMA. A comparative study concerning FDA approvals versus European CE mark (from 2000 to 2011) for the innovative and potentially risky medical technologies suggested that the same devices have been approved and made available to patients in Europe three or more years before devices are approved in the US. [5] ,[6]These data, although interesting from a historical perspective, are not necessarily relevant anymore. With the new medical device regulation in Europe coming into force in 2020, things will probably change dramatically. New research will need to be conducted to compare the typical timelines needed to receive FDA approvals versus CE mark.
[1] National Institutes of Health. Smoking linked to higher risk of peripheral artery disease in AfricanAmericans. Available at: https://www.nih.gov/ news-events/news-releases/smoking-linkedhigher-risk-peripheral-artery-disease-africanamericans (accessed 12 February 2019).
[2] US FDA. Eluvia drug-eluting vascular stent system – P180011. Available at: https://www.fda.gov/MedicalDevices/ ProductsandMedicalProcedures/ DeviceApprovalsandClearances/RecentlyApprovedDevices/ucm621897.htm (accessed 12 February 2019).
[3] S Müller-Hülsbeck, K Keirse, T Zeller, et al. ‘Long-term results from the MAJESTIC trial of the ELUVIA paclitaxel-eluting stent for femoropopliteal treatment: 3-year follow-up’. Cardiovasc Intervent Radiol 2017;40:1832–1838.
[4] S Muller-Hulsbeck. Drug-eluting stents — new developments and established data. Presented at CIRSE;2016. Barcelona, Spain. 10–14 September 2016.
[5] TJ Hwang, E Sokolov, JM Franklin, AS Kesselheim. ‘Comparison of rates of safety issues and reporting of trial outcomes for medical devices approved in the European Union and the United States: Cohort study’. British Medical Journal 2016;353:i3323.
[6] DB Kramer, S Xu, AS Kesselheim. ‘Regulation of medical devices in the United States and European Union’. The New England Journal of Medicine 2012;366:848–855.
