Dyslipidemia therapy takes a step forward

In medical technology development, there are perennially long-shot technologies being pursued for their ability to make an order of magnitude shift in treatment.  This, of course, seems to be the thrust of a majority of biotechnology development, which seeks to provide cures where only palliative treatments (drug or device) currently exist, such as in gene therapy and stem cell therapy.  

But on a more practical level (i.e., well within the next ten years), examples include non-invasive blood glucose monitoring in diabetes, the development of effective dyslipidemia therapy and others.  On that note, the development of Esperion Therapeutics' ETC-1002 took a step forward this past week, with the commencement of a Phase I clinical trial of the drug.

Dyslipidemia therapy, as its name connotes, is an approach to treating coronary heart disease not by coronary bypass, angioplasty or any physical device treatment to remove atherosclerotic plaque from clogged arteries, but by targeting the underlying metabolism of lipids that has produced those plaques, with the ultimate goal of reducing plaques non-invasively. 

An effective non-invasive treatment of atherosclerosis poses a significant threat to palliative treatments.  It may be a bit cliche to reduce the argument to the attractiveness of taking a pill instead of undergoing surgery, but that scenario is not far from the truth. Such a prospect puts the entire industry of device treatments for coronary artery disease (CAD) on notice.

For the time being, coronary stents still represent one of the best minimally invasive avenues for patients with CAD.  (See our report.)

DES and other coronary artery disease treatment tech trends

A steady rate of technology development in coronary stents, producing an equally steady stream of new stent market introductions, is focused on expanding aggregate stent caseload (through penetration of what would otherwise be coronary artery bypass caseload) or shifting the balance even further toward concentration of stents sales to the drug-eluting stent (DES) variety.  While unit volumes are on the rise, pricing pressures have dampened this overall market growth and will continue to put a squeeze on stent margins.  This trend has been in force for the past two years (since the late stage thrombosis scare subsided), but going forward there will be more significant forces and developments impacting the stent market, principally the emergence of novel stent technologies like bioabsorbable stents, the emergence of drug-eluting balloons and the development of other anti-restenosis or anti-atherosclerosis options.  These dynamics are the focus of the MedMarket Diligence report #C245, the post below being a brief excerpt from that report.

The evolution of the coronary stent market has been driven by manufacturers focused on expanding the use of coronary stents into new caseload as well as penetrating the market shares of competitors.  

Clinicians, for their turn as gatekeepers in this effort, are guided in the adoption of stent technologies by the availability of clinical evidence supporting expansion of stent use to patients whose coronary heart disease might otherwise be addressed by coronary artery bypass graft (CABG) surgery, with their selection of the specific stent used determined (to the extent that price is not an overriding attribute) by how well each stent's clinical data stands up under scrutiny of possible clinical complications.

Manufacturers then take a hard view of both cost and complication rates.  Below are shown the potential complications ensuing from stent implantation and which have therefore become a focus of stent technology development:

Potential Complications Related to Implantation of Cardiovascular Stents


Source: MedMarket Diligence report #C245, "Worldwide Market for Drug-Eluting, Bare Metal and Other Coronary Stents, 2008-2017."  

Some novel stent technologies are under development by: AdvanSource Biomaterials, Allvivo Vascular, Inc., Blue Medical Devices, CeloNova BioSciences, Hexacath, InspireMD, ITGI Medical Ltd., Miami Cardiovascular Innovations (MCVI), MoBeta, Inc., Nexeon MedSystems, Inc., OrbusNeich, Palmaz Scientific, and Prescient Medical.  Other technology developments in coronary artery disease treatments, beyond stent technologies, are also addressed in report #C245.  

Download report #C245, "Worldwide Coronary Stent Market, 2008-2017," PDF — $2,850.00
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Coronary artery disease: stents, bypass — and plenty of other options

Because of the invasive nature of cardiac surgery, medical therapy will always be the preferred treatment protocol favored by many clinicians. To that end, device and pharmaceutical manufacturers continue to explore methods of treating atherosclerosis that will render surgery unnecessary.

For instance, researchers at the Medical University of Graz in Austria announced in February 2009 (Journal of Lipid Research, 50:312-326) progress related to their study of a synthetic atherosclerosis drug that can reduce the build-up of plaque without producing the side effect of fatty liver disease, which can lead to other disorders such as diabetes. However, in some instances, more aggressive therapy is required and for those patients, there is a host of therapy choices available — all of which can prove to be competitive with stenting technology.

The range and diversity of alternatives for treatment of acute coronary artery disease are striking:

  • angioplasty with or without stenting
  • atherectomy
  • coronary artery bypass grafting
    • open CABG
    • off-pump CABG
    • MIDCAB (minimally invasive direct coronary artery bypass)
    • RACAB (robotic assisted coronary artery bypass)
    • other CABG
  • genetic therapies
  • transmyocardial laser revascularization
  • HDL therapy
  • drug-eluting balloons
  • nanoparticles and other agents

While the caseload distributed across these alternatives is concentrated in angioplasty (with stenting) and coronary artery bypass grafting, the acute nature of coronary artery disease, the size of the caseload and the continued pressure on clinicians to reduce the associated trauma of treatment give incentive to developers seeking to produce better outcomes.

The MedMarket Diligence report #C245 is described at http://www.mediligence.com/rpt/rpt-c245.htm and details the worldwide market for the use of alternative stent devices in the treatment of coronary artery disease. The report assesses the treatment of coronary artery disease by alternative treatment methodologies (percutaneous intervention with or without stenting, coronary artery bypass grafting alternatives and other medical/surgical treatment options), with estimated current/forecast caseload across treatment types.

The report is described at this link. The report may be ordered for immediate download online.

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Coronary stent market opportunity

Stenting is not ideal for all patients with coronary heart disease, such as those with left main or three (or more) vessel disease. However, the vast majority of cardiovascular disease patients can benefit from the benefits of PCI, not the least of which include a shorter recovery period and less trauma to the patient.

The global market for coronary stents is over $7 billion and growing steadily. With the average age of citizens in developed countries increasing, there is an increased need to provide medical care to the average citizen. As such, an aging population translates into increasing numbers of people needing medical therapy and increasing numbers of people who need more aggressive medical therapy due to the aging process. As the population of developed countries ages, the number of percutaneous coronary interventions (PCIs) required increases as well. Currently, the incidence of PCI procedures (sometimes referred to as percutaneous transluminal coronary intervention or PTCA) is increasing at a rate of 3%–5% worldwide. Today, the vast majority of PCIs involve the implantation of one or more coronary stents.

Until the advent of coronary stents, patients with cardiovascular blockages had little choice but to either keep a close eye on their disease (“watchful waiting” with or without accompanying pharmaceutical therapy) or undergo coronary artery bypass grafting (CABG). When angioplasty was developed by Andreas Gruentzig in 1977, patients were presented with the option to undergo angioplasty in an effort to open blocked coronary arteries. While short-term benefits were usually seen with balloon angioplasty, longer-term outcomes showed many arteries re-closing and requiring repeated intervention; up to 50% of angioplasty patients were found to require further angioplasty within six months. In an effort to reduce the frequency of patients requiring reintervention, scientists and clinicians developed stents that could be left behind to hold the artery open once the PTCA balloon was withdrawn.
Unfortunately, clinicians found that bare metal stents (BMS) could cause an immunological response that would try to “protect” the body from the foreign material (i.e., the stent). This, in turn, would lead to further narrowing near to or inside the stent, as seen in roughly 25% of patients receiving BMS devices. To combat this, drug-eluting stents (DES) were developed. 

Drug-eluting stents were developed to release a drug (e.g., sirolimus or paclitaxel) intended to reduce the incidence of restenosis. From there, even more innovative products have been developed, such as bioactive stents or stents designed to attract a patient’s own endothelial cells to coat the stent (as in devices by OrbusNeich, Hexacath, and Miami Cardiovascular Innovations).

Other device developers have sought to create stents that will fully degrade and disappear over a period of weeks or months—of a score of companies in this area, Abbott Vascular, Biotronik and REVA Medical appear closest to market. Yet others seek to abandon the use of stents altogether, opting instead to pursue an angioplasty balloon that will leave the anti-inflammatory drugs behind without the accompanying stent, as with CE Mark approved devices by EuroCor (the DIOR catheter) and B. Braun Melsungen (the SeQuent Please catheter).

Because the ultimate therapy has not yet been found, many opportunities still exist for effective therapies to combat atherosclerosis. So far, coronary stents hold the most promise for effectively treating an aging population with an increasing incidence of coronary artery disease.

See also, "Worldwide Coronary Stent Market, 2008-2017" at link.

Krucoff: Second-Generation Drug-Eluting Stents Better at Anti-Restenosis

The improvements in stent flexibility and biocompatibility have lead to the conclusion by Dr. Mitchell Krucoff that second-generation drug eluting-stents, such as Abbott's Xience stent, result in an improved ability to prevent restenosis following angioplasty and stent implantation. See an excerpt from India's pharmabiz.com (which also highlights the market potential for coronary stents in India):

Newer drug eluting stents (DES) are proving to be significantly more effective and safer compared to the 'first-generation' drug eluting stents. DES is developed to reduce incidents of re-blockage or restenosis which occur with bare metal stents and almost all trials showed a marked reduction in restenosis rates. The ideal drug eluting stent is one which demonstrates high efficacy while maintaining excellent safety profile. The latest stents made of polymer and steel are known for higher biocompatibility. These are thinner in appearance and more flexible. The lower doses of the drug are much preferred as a long treatment option for complex and difficult cases. Another big advantage is the negative side effects. The drug eluting stents reduced the need for a second intervention procedure by about 40 to 50 per cent compared to bare metal stents especially in complex cases where patients reported long blockages in diabetics and those having small blood vessels, according to Dr Mitchell Krucoff, interventional cardiology scientist and advisor to US FDA on medical devices. See more at link

See Worldwide Coronary Stent Market, 2008-2017.

Coronary stents: Big differences in adoption globally

Market drivers that vary geographically account for some big differences in the distribution of the coronary stent market across the currently available stent types, and these differences will continue when bioabsorbable stents (and others) are introduced to the market over the next few years.

The local market forces dictating these differences include:

  • Regulatory timelines in one market that can delay new product introductions by a year or more compared to another market
  • Regulatory control that either limits or facilitates introduction of local market ("me too") stent developers.
  • Differences in clinical adoption of advanced technologies driven by local practice patterns
  • Price sensitivities that can vary considerably from one geography to the next, with the potential to severely restrict the adoption of advanced technologies and/or force price reductions

The coronary stent market illustrated distinct differences in market segmentation on the basis of geography, challenging assumptions of the expected market shares of current and potential stent manufacturers competing in each local market.  One of the most distinct differences is the relative adoption of drug-eluting stents in China (captured in Asia/Pacific, below) versus either the U.S. or Europe. 

Source: MedMarket Diligence, LLC.  Report #C245, "Worldwide Coronary Stent Market, 2008-2017."

What medtech company isn’t globally focused?

My posts on advanced medical technology, drawing frequently from our market reports, are worth emphasizing for their global perspective.  Some two decades ago, it became apparent to me that that the global market perspective is not reserved for big, multi-national companies and their global presence.  My understanding of this came about from the experience of seeing clients of all sizes showing their interest — their compelling need — to examine markets outside the U.S.  Whether trends like the formation of the European Union and the easing of trade across its member states’ borders, the odd appearance of market economies under Communist China, the economic development of democratic states in South America or even the emergence of newly accessible markets in Eastern Europe — too many changes were making it such that medium or even small sized companies could not overlook opportunities beyond their domestic borders.

Now, I would find it rather striking to see a company focusing its efforts on only one country.  As a corollary, I find it equally striking that some market analyses are still peddled that focus only on specific countries.  Certainly, I understand the somewhat misguided incentive to do so — it’s easier to focus on one country, one set of patient demographics, one set of regulatory challenges. 

Yet, for the cost of product development, the consistent demand by patients for therapeutic outcome regardless of where they live, the available channels to get products into new countries, the ease with which competitors’ innovations will make it cross-border — it simply makes no sense to focus on one particular market.

So I rarely find the need among savvy clients to pressure them into broadening their perspective.  They have already long since reinforced the premise, to me, that the information they seek on medical markets is not complete unless it considers the global perspective. 

Because if they don’t get a good handle on global markets, they will promptly lose advantage to their competitors.