Category Archives: stem cell

Applications, global markets in tissue engineering and cell therapy

Screen Shot 2014-04-17 at 7.37.44 AMThe market for tissue engineering and cell therapy products is set to grow from a respectable $8.3 billion in 2010 to nearly $32 billion by 2018. This figure includes bioengineered products that are themselves cells or are actively stimulating cell growth or regeneration, products that often represent a combination of biotechnology, medical device and pharmaceutical technologies. The largest segment in the overall market for regenerative medicine technologies and products comprises orthopedic applications. Other key sectors are cardiac and vascular disease, neurological diseases, diabetes, inflammatory diseases and dental decay and injury.

Cell-tissue-applications

Factors that are expected to influence this market and its explosive growth include political forces, government funding, clinical trial results, industry investments (or lack thereof), and an increasing awareness among both physicians and the general public of the accessibility of cell therapies for medical applications. Changes in the U.S. government’s federal funding of embryonic stem cell research has given a potentially critical mass of researchers increased access to additional lines of embryonic stem cells. This is expected to result in an increase in the number of research projects being conducted and thus possibly hasten the commercialization of certain products.

regional-forecast

Source: Report #S520, “Tissue Engineering, Cell Therapy and Transplantation: Products, Technologies & Market Opportunities, Worldwide, 2009-2018.”

Another factor that has influenced the advancement of regenerative technologies is found in China, where the Chinese government has encouraged and sponsored cutting-edge (and some have complained ethically questionable) research. While China’s Ministry of Health has since (in May 2009) established a policy requiring proof of safety and efficacy studies for all gene and stem cell therapies, the fact remains that this research in China has spurred the advancement of (or at least awareness of) newer applications and capabilities of gene and stem cell therapy in medicine.

Meanwhile, stricter regulations in other areas of Asia (particularly Japan) will serve to temper the overall growth of commercialized tissue and cell therapy–based products in that region. Nonetheless, the growth rate in the Asia/Pacific region is expected to be a very robust 20% annually.


MedMarket Diligence’s Report #S520 remains the most comprehensive and credible study of the current and project market for products and technologies in cell therapy and tissue engineering.

Growth in Sales of Products in Cell Therapy and Tissue Engineering

Tissue engineering and cell therapy comprise a market for regenerative products that has been growing and will continue to grow at over 20% annually through 2018. This market spans many specialties, the biggest of which is therapies for degenerative and traumatic orthopedic and spine applications. Other disorders that will benefit from cell therapies include cardiac and vascular disease, a wide range of neurological disorders, diabetes, inflammatory diseases, and dental decay and/or injury. Key factors expected to influence the market for regenerative medicine are continued political actions, government funding, clinical trials results, industry investments, and an increasing awareness among both physicians and the general public of the accessibility of cell therapies for medical applications.

The current high rate of growth in cell therapy and tissue engineering product sales is due to the confluence of multiple market drivers:

  • Advances in basic science revealing the nature of cell growth, differentiation and proliferation
  • Advances by industry to manipulate and determine cell growth toward specific therapeutic solutions
  • Low barrier to entry for competitors in the market
  • Broad range of applications of cell/tissue advances to many different specialties with modest adaptation needed
  • Strong venture funding

The dominant clinical area driving cell therapy and tissue engineering product sales is orthopedics and musculoskeletal, wherein bone grafts and bone graft substitutes are well-established. Below is the projected balance of cell therapy and tissue engineering product revenues by clinical area through 2018.

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Source: MedMarket Diligence, LLC; Report #S520.

While orthopedics, musculoskeletal and spine applications will remain a huge share of this market, more growth is coming from cell/tissue products in most other areas, which have only recently (within the last five years) begun to establish themselves.

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Source: MedMarket Diligence, LLC; Report #S520.

Fundings in Medtech 2009-2014: A Contrarian View

Since 2008, medtech has taken a lot of hits. Indeed, when the capital crunch hit, medtech was not viewed as the safest place for investment by a suddenly very risk averse world. Blue chip stock, high volume, low growth, STABLE markets became the norm for a lot of money. But, after a short while, it became apparent that medtech was hardly junk bonds or penny stock, especially considering the battle-hardened innovators of medtech who continued to seize on innovations that provided treatment where there once wasn’t, that accelerated healing, that measurably improved outcomes, that resulted in real cost savings to health systems and insurers, that, in other words, met DEMAND.

So, money came back to medtech. I tracked it then, and I track it now, month by month, funding by funding, company by company. Was it coming back in the pollyanna-esque windfalls of biotech and pharma? No, and I don’t think it ever has or ever will — nor should it. Biotech seems to perennially able to tap the “hope springs eternal” deep pockets of venture capital that can regularly draw individual fundings of $50 million, $75 million or $100 million. Pharmaceuticals don’t seem to go to the VC well as often, but when they do, their funding rounds are no less spectacular.

Medtech excels at crafting plain and simple solutions to disease, suffering, high healthcare costs and clinical need. Not every solution is a blockbuster — in fact, there are more than a few 510(k) products that should probably just be called “me, too”, since they do not distinguish themselves independently, at least not from a clinical or technology standpoint. But medtech has proven its ability to keep pushing the treatment envelope by innovating a little further to gain a bit more edge on outcome or cost or both.

So, medtech regularly pulls in $5 million, $10 million, $25 million at at time — frequently less, but not infrequently more.

My Contrarian View. But let me highlight again that medtech is a moving target and not everyone is thinking apples to your oranges.  What I consider medtech is, at its root, technologies that were traditionally represented as medical device treatments for disease and trauma. (And, yes, so I don’t have to answer this later on, by “medical device” I mean implants, instruments, instrumentation, even capital equipment.)  But medtech is not only medical device, for it is also (at least by my authoritarian definition, since this is my blog, but it is read by many in this field), anything and everything (within reason) that is either adjunctive to medical devices like drug delivery, like biomaterial-based implants/grafts, drug/device hybrids, tissue engineering and cell therapy (this latter is perhaps at the fringe of medtech, bordering on pure biotech).

Where’s the boundary of medtech? In my mind, it is anything and everything that competes with markets that have in the past and are to some extent still served by medical devices, equipment and supplies. For the sake of repetition, this is the definition I have posted on the medtech fundings I report on month by month in this blog (and in the online spreadsheets linked here):

What is “medtech”?: We view medical technology (medtech) as principally medical devices and equipment, but also all technologies that are directly competitive with or complementary to technologies represented by therapeutic or diagnostic medical devices/equipment.

Note: Historic coverage of “medtech” has been limited to medical devices, supplies and equipment. We feel that such a limited definition poorly reflects the true nature of the markets that once were limited to such products. In reality, assessing the markets and competition for medical devices by ONLY considering other medical devices would result in gross underestimations of both competition and market potential. Moreover, this is reflected in both the nature of medical devices (which may be hybrid device/bio/pharm products or products that may not be “devices” at all (especially in the typical definitions defined by material type and function) but that compete head-on with devices.

So, on this more liberal definition of medtech (which some still feel is too restrictive), I can point to a steady stream of investments that has been on an upward trend for the last five years. If you disagree, feel free to come up with your own definition(s), but here is the five year trend of medtech investment:

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Source: MedMarket Diligence, LLC

Looked at from a seasonal standpoint, this data is shown below:

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Source: MedMarket Diligence, LLC

The monthly data underlying both of these charts is at link. If that is not enough data for you, then you can look at a comprehensive listing of the individual fundings behind this at link.

Global and regional growth rates for wound care product sales

Manufacturers of wound care products, from traditional dressings and bandages to growth factors and bioengineered skin, see variable sales growth driven by different levels of new product adoption, variations in clinical practices, and other technology, reimbursement, regulatory, economic and other forces that vary by geography across the globe. The balance of sales across multiple wound care product types can be radically different from country to country and region to region.

Emerging from the 2013 analysis (Report #S249) by MedMarket Diligence are the current and forecast wound care product sales resulting from the net effect, region by region, of these multiple forces. Below is illustrated the high growth country/product segments in wound management, reflecting the rapid adoption of new technologies such as growth factors and bioengineered skin, as well as older products such as alginates that are gaining sales in rapidly developing economies.

wound-country-high

Source: MedMarket Diligence, LLC; Report #S249, “Wound Management, Worldwide Market and Forecast to 2021: Established and Emerging Products, Technologies and Markets in the Americas, Europe, Asia/Pacific and Rest of World.”

At the other end of the extreme are those very well established products growing at less than anemic rates in countries where the economy is not as robust and/or where the growth has been superseded by sales of more novel products. Conventional dressings and bandages offer considerably less demand than do growth factors, bioengineered skin and skin substitutes and similar new products.

wound-country-low

Source: MedMarket Diligence, LLC; Report #S249

Of course, growth of sales in wound management products (and any product) is defined as the percentage change in sales volume over time. Smaller markets (typically soon after they have formed as a result of their initial commercialization) tend to grow on a percentage basis much faster. Indeed, a $1 dollar sale in year 1 followed by a $2 sale in year 2 represents a 100% growth rate, while a $1 increase in sales from year 1 to year 2 for a $100 million market represents virtually zero growth. Conversely, a 1% increase in a $1.75 billion market is a $17.5 million increase. This is indeed obvious, but must be kept in mind when considering the growth rates discussed above.

The Real Future of Medtech: An Opinion

I see graphics (and, please help me, “infographics”) on the the future of medtech. These are graphics produced most often by analysts who are walking backward looking at their feet; in other words, living by the tenet of “past is prologue”. The leading companies of five years from now can be simply predicted by a 5-year extrapolation of last year’s revenue growth.  Has “forecasting” really simply become a distillation of “more of the same”?

The future of medtech is dictated far more importantly by not what has already happened, or some expectation that past trends will simply continue on into future trends, but by what has not happened yet. The major thrust of any significant growth (and isn’t growth that in which we are most interested?) comes primarily from events that have not yet happened. Do you want to be Steve Jobs or Steve Ballmer?  Do you want to create demand or belatedly follow it?

If you have a short-sighted or narrow view, then you consider your competitors all who do what you do but who do it better, faster or cheaper. If you have a long view, you consider what might be possible based on available/emerging technology to tap into untapped demand or simply create latent demand that no company has yet been sufficiently visionary or innovative to seize.  What patient populations, clinical practice patterns and their trends are the pulse that you monitor (or are you even monitoring these)?  There is a gap between what is available and a whole set of patients virtually untreated, physicians unsatisfied, and third party payers struggling.  Are you an angioplasty catheter manufacturer — or a coronary artery disease solution?  Do you make devices — or outcomes?

Look at staid “device” companies like Baxter International and see that they have “biosurgery” divisions.  Look at Medtronic and appreciate that they are as sensitive to developments in glucose monitoring and insulin pump technologies as they are to the litany of cell therapy approaches under pursuit.

Virtually every area of current clinical practice is subject to change when considering drug/device hybrids, biomaterials, nanotechnology/MEMs devices and coatings, biotechnology, pharmaceutical (and its growing sophistication in drug development), western medicine and eastern medicine, healthcare reform, cost containment, RFIDs, 3D printing, information technology  – we hope you see the upside in this and not just the downside.

Of course companies, especially public ones, must consider the revenue streams in both Year 0 and Year 5, but if the focus is only on Year 0, then that number will also be the ROI in five years.

 

 

Type 1 diabetes addressed by “silencing immune attacks” (Children’s Hospital, Boston)

Researchers at Children’s Hospital in Boston have reported in the online edition of Diabetes that they have identified the specific molecular pathway involved in triggering the autoimmune response at the root of type 1 diabetes. The research team studied “hundreds” of pathways in animals with diabetes and ultimately identified one, known as ATP/P2X7R, which triggers the immune system’s T-cell attacks on the pancreas that subsequently prevent the pancreas from producing insulin.

While this research is akin in some ways to many disease research discoveries that are dramatic but that have not led to cures or significant advances in treatment, the discovery of the root pathway in type 1 diabetes is significant for the fact that it opens up the possibility of, on the one hand, interrupting this pathway in order to the autoimmune destruction of patients’ insulin-producing islet cells and, on the other hand, interrupting this pathway to similarly prevent destruction of islet transplant cells. It may well be years before this leads to treatment options, which may include “drug therapies to transplants that require less immunosuppression” for patients with existing type 1 diabetes and options to even prevent type 1 from developing in children.

Medtech from incremental to quantum leap advances

Advanced medical technologies become advanced by the application of innovation that results in more effective, less costly or otherwise arguably better outcomes (including reduced risk of complications or disease recurrence) for patients, including in some cases enabling treatment when none was previously possible. It is intrinsic to every entrepreneur that the idea he/she is pursuing accomplishes this.

Manufacturers of products on the market have an imperative to either improve upon those products or make them obsolete. This imperative is manifested in a spectrum of planned innovation from simple incremental innovations to the quantum leap of a radically new approach.

There is an enormous amount of technology development, often applicable to multiple different clinical applications, that will be realized in product markets in the future. For the moment, though, I would like to look beyond “incremental improvements” or “product line extensions” or other marginal advances that serve little more than superficially addressing shortcomings of existing products on the market. I would like to look at waves of innovation coming in the short to long term that are expected to impact medtech in ways that are increasingly “radical” or represent varying orders of magnitude of improvement in results.

Three categories spanning short, mid, and long reflect what I see in medtech development. Below, I outline the nature of each and the specific examples that are or will be emerging.

Short term. With change encompassing technologies that are just sufficiently different so that they cannot simply be called incremental innovations, some short term advances often combine two or more complementary and/or synergistic technologies in new ways to advance healthcare. Examples include:

  • Image-guided surgeries to augment the surgeon’s ability to navigate complex anatomy or discern the margins of healthy versus disease tissue.
  • Natural orifice endoscopic surgery (and shift in general from invasive to interventional and intraductal procedures) to either drastically reduce or eliminate the trauma of surgical access
  • Non-invasive therapeutics (like lithotripsy, gamma knife, others) to treat disease without trauma to collateral tissues.
  • Genome-driven treatment profiling (prescreening to determine ideal patients with high probable response).
  • Personalized (custom) implants. These already exist in orthopedics, but the potential for customized implants in gastroenterology, cardiology, and many other clinical areas is wholly untapped.
  • Regenerative technologies (bone, skin, other). These technologies represent introductory markets with lowered challenge compared to more complex functional anatomy (e.g., vital organs).
  • Smart devices (implantable sensors, RFID-tagged implants, etc.) to provide data to clinicians on implant location and status or, in the extreme respond diagnostically or therapeutically to changes in the implant’s immediate environment.

Mid-term. These are new therapeutic options that are fundamentally different than those in current use for a given treatment option. These are technologies that have demonstrated high probability of being feasible in large scale use, but have not yet accumulated enough clinical data to warrant full regulatory approval.

  • Nanotech surface technologies for biocompatibility, localized treatment delivery or other advantages at the interface between patient and product.
  • Materials that adapt to changes in implant environment, to maintain pH, to release drugs, to change shape.
  • Artificial heart. A vital organ replacement that currently has demonstrated the capacity to be a bridge to transplant but has also advanced sufficiently to open the possibility of permanent replacement in the not-too-distant future.
  • Cell/device hybrids. These are organ replacements (e.g., kidney, lung, liver) performing routine function or natural organs, but configured in a device to address unresolved issues of long term function, immune response and others.
  • Artificial organs (other than heart) — closed loop glucometer/insulin pump (artificial pancreas). These are not even partial biological representations of the natural organ, but completely synthetic “organs” that intelligently regulate and maintain a steady state (e.g., blood glucose levels) by combining the necessary functions through combined, closed-loop mechanical means (an insulin pump and glucometer with the necessary algorithms or program to independently respond to changes in order to otherwise maintain a steady state.

Long-term. Orders of magnitude, quantum shift, paradigm shift or otherwise fundamentally different means to serve clinical need.

  • 3D implant printing. In a recent example, in an emergency situation a 3D implant for repair of a infant’s trachea was approved by the FDA. These implants, as in the case of the trachea repair, will most often be customized for specific patients, matching their specific anatomy and may even include their (autologous) cells. They may also be made of other materials including extracellular matrices that will stimulate natural cell migration followed eventually by bioabsorption of the original material. Depending upon type of material and complexity of the anatomy, these technologies may emerge in the near or distant future.
  • Gene therapies. Given the root cause of many diseases has a genetic component or is entirely due to a genetic defect, gene therapies will be “permanent corrections” of those defects. An enormous number of hurdles remain to be crossed before gene therapies are largely realized. These deal with delivery and permanent induction of the corrected genes into patients.
  • Stem cell therapies. The potential applications are many and the impact enormous of stem cell therapies, but while stem cell technology (whether for adult or embryonic) has made enormous strides, many challenges remain in solving the cascade of differentiation while avoiding the potential for aberrant development of these cells, sometimes to proliferative (cancerous) states.
  • “Rational” therapeutics. Whether by stem cell therapies, gene therapies or other biochemical or biological approach, “rational” therapeutics represent the consummate target for medical technology. Such therapeutics are “rational” in the sense that they perfectly address disease states (i.e., effect cures) without complication or need for recurrent intervention.

There are certainly more holes than fabric in this tapestry of short-, mid- and long-term technology innovation, but this should serve to illustrate the correlation between the sophistication of the potential medtech solution and the level of technical challenge in order to achieve each.