Frost & Sullivan expects global drug-eluting stent market revenue to reach $6.36 billion by 2020. Read more about the tremendous change happening in the stent market.
The stent market is in the midst of tremendous change as bare-metal stents, the first generation of stent products, are replaced by drug-eluting stents. Frost & Sullivan expects global drug-eluting stent market revenue to reach $6.36 billion by 2020. A convergence of material, pharmaceutical, biotechnology and medical device companies is spawning product innovations revolving around improvements on three fronts: platform design, coatings and the type of added pharmaceutical agent.
Stent Design: A Generational Change
First-generation stents are hollow, mesh-like devices with bare-metal surfaces—usually clinical-grade stainless steel or a biocompatible alloy such as nitinol (nickel-titanium)—that offer mechanical support to diseased vessel walls. They also help in endothelialization and gradual rebuilding of the vessel wall. However, the bare-metal surface often contributed to thrombosis, or clot formation, and localized inflammation requiring systemic administration of anti-inflammatories and antiproliferatives. Once the default choice, bare-metal stents are now on the decline.
In order to overcome the limitation of poor bioavailability of systemic antiproliferative medications, drug-eluting stent products have the drug component added to the metallic stent platform—usually encapsulated by a polymer coating. As the polymer degrades, the stent releases antiproliferative agents to combat restenosis. The persistent threat of thrombosis requires a yearlong follow-up medication, known as dual anti-platelet therapy. This cocktail of antiproliferatives adds to the cost of care and length of rehabilitation and recovery.
Then came the discovery of bioabsorbable stents. The idea is to remove the metallic component for a completely biodegradable stent that eliminates the chance of thrombosis or inflammation and the need for dual anti-platelet therapy. The product would gradually degrade, giving mechanical support following a percutaneous transluminal coronary angioplasty procedure and dissolving as the vessel strengthens. Products such as ABSORB® BVS from Abbott Vascular (CE marked and U.S. Food and Drug Administration (FDA) approved) and DESolve® BRS from Elixir Medical (CE marked) are examples of bioabsorbable stents. Despite being touted as the replacement for drug-eluting and bare-metal stents, the innovation has not met market expectations: it failed to demonstrate its theoretical advantages and has a significantly higher rate of target vessel myocardial infarction.
Other emerging stent technologies are discussed below.
A proposed solution to the challenge of restenosis is to coat the stent surface with endothelial cells or their progenitors (stem cells), or other factors such as antibodies that would attract endothelial cells to the diseased area. The bioactive layer could inhibit inflammatory response, speed up the process of endothelialization and tissue repair, and eliminate the need for drugs and their potential side effects.
The Combo Dual Therapy Stent from OrbusNeich USA employs this principle. It has an abluminal coating of sirolimus and a biodegradable SynBiosys polymer. The biological coating on the outer surface immediately captures endothelial progenitor cells and initiates the formation of an endothelial layer to accelerate the healing process and return of functionality in patients with coronary stenosis, and reduce adverse events in the long term. The Combo Dual Therapy Stent is CE marked and is in clinical trial stages in the United States.
Gene-eluting stents are similar in principle to drug-eluting stents. Instead of a coating of drugs, the stent surface is coated with genes that will aid tissue regeneration. Utilizing nanotechnology, the sustained and localized delivery of genes is expected to mitigate problems of restenosis and late-stent thrombosis by accelerating the regenerative capacity of re-endothelialization. However, a major limitation of this system is ineffective localization of the genes. Despite innovations in nanotechnology, such as nanoparticle vehicles, and in vector biology (biomaterial, viral and non-viral vectors) for gene delivery, design will remain a major challenge. A gene-eluting stent cannot be an off-the-shelf device, but rather must be customized for individual patients. While significant academic research on the concept has happened in the past decade and small and large preclinical models have shown promising results, no human data is available yet. Academic and medical device industry collaborations could overcome some of the challenges for clinical translation.
“Stent coatings” is a broad term that encompasses surface coatings and modification approaches to make the stent product more biocompatible and clinically effective. The coating approach can be polymeric, non-polymeric or biologic (e.g., proteins or antibodies). An ideal stent coating can help achieve biocompatibility and hemocompatibility and reduce adverse effects by inhibiting thrombus formation, preventing inflammatory reaction and proliferation of smooth muscle cells, and facilitating the process of re-endothelialization.
Nanotechnology and inorganic surface coating technologies are widely used in stent products. For example, polyzene-F® is a biocompatible nanocoating developed by Celonova Biosciences. The company’s Cobra PzF system recently received FDA clearance and is also CE marked. The nanocoated stents are proven to be thrombo-resistant and anti-inflammatory with rapid healing effects, which means it leads to a much faster, natural healing of the artery and also would reduce the need for long-term blood-thinning medication.
What’s the Future?
Successive generations of drug-eluting stent products have greatly benefited from advances in nanotechnology. Nanoparticles for drug delivery especially have propelled the products to the forefront, giving them better degradation kinetics and bioavailability. Biomimetics will gain importance in making the stent surface more biocompatible and better-suited for immune acceptance. Polymers and biomaterials will also play a vital role in stent architecture. Better degradation dynamics, biocompatibility and uniform coating distribution will make the stent more functional. Incorporating biocompatibility polymers into the platform will be crucial in the long term as the industry sees an influx of biodegradable stents. Polymeric and non-polymeric stent coatings will counter the value proposition of bioabsorbable stents.
The advent of drug-eluting stents has brought medical device and pharmaceutical companies closer, ensuring better and more efficient collaborations to pursue faster approvals. Licensing drug formulations has become the industry norm, opening more avenues for collaboration and co-creation. A few stent companies have started developing drugs in-house, and have also partnered with academia and research labs for licensing options.
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