In past blog posts, we have noted multiple naturally-occurring substances or methods for strong adhesion that are being investigated for their potential to be exploited for medical or surgical adhesion. These include adhesives from remora, mussels, geckos, crab shells, Australian burrowing frogs, spider webs, porcupine quills, sandcastle worms.
Researchers from MedUni Vienna and Vienna University of Technology are now investigating 300 different ticks for the “cement” used by the parasites to attach to hosts. The goal is to study the composition of the natural tick “dowel” used by the mouthparts of ticks and determine how it might serve as a template for new tissue adhesives.
The Vienna research also notes other natural adhesives are similarly being investigated for medical and surgical use:
Other potential “adhesive donors” are sea cucumbers, which shoot sticky threads out of their sac; species of salamander, which secrete extremely fast-drying adhesive out of skin glands, if attacked; or insect larvae, which produce tentacles or crabs, which can remain firmly “stuck,” even under water.
The incentive for studying natural adhesives is that they have been evolutionarily developed to provide very strong adhesion without toxicity in various wet or dry conditions that are challenging for existing synthetic or natural glues (e.g., fibrin glues, cyanoacrylates, etc.).
MedMarket Diligence has tracks the technologies, clinical practices, companies, and markets associated with medical and surgical sealants and glues, with the most recent coverage in, “Worldwide Markets for Medical and Surgical Sealants, Glues, and Hemostats, 2015-2022,” (report #S290).
The bulk of medical/surgical glues are biologically-based, and soon the bulk of medical glue sales will come from Asia/Pacific.
The two graphs below show the changes in regional shares in biologically-based glues. It can be seen that from 2015 to 2022, the US and Asia-Pacific will practically switch places in terms of revenue share per region. This significant change will come about because of the intensive and enormous healthcare modernization taking place in the PRC. In 2012, the Chinese government announced its 12th five-year plan which includes the construction of 20,000 new hospital and healthcare facilities.
Source: Worldwide Markets for Medical and Surgical Sealants, Glues, and Hemostats, 2015-2022: Established and Emerging Products, Technologies and Markets in the Americas, Europe, Asia/Pacific and Rest of World (Report #S290).
Medtech and biotech investment is driven by an expectation of returns, but rapid advances in technology simultaneously drive excitement for their application while increasing the uncertainty in what is needed to bring those applications in the market.
MedMarket Diligence has tracked technology developments and trends in advanced medical technologies, inclusive of medical devices and the range of other technologies — in biotech, pharma, others — that impact, drive, limit, or otherwise affect markets for the management of disease and trauma. This broader perspective on new developments and a deeper understanding of their limitations is important for a couple of reasons:
Healthcare systems and payers are demanding competitive cost and outcomes for specific patient populations, irrespective of technology type — it’s the endpoint that matters. This forces medical devices into de facto competition with biotech, pharma, and others.
Medical devices are becoming increasingly intelligent medical devices, combining “smart” components, human-device interfaces, integration of AI in product development and products.
Medical devices are rarely just “medical devices” anymore, often integrating embedded drugs, bioresorable materials, cell therapy components, etc.
Many new technologies have dramatically pushed the boundaries on what medicine can potentially accomplish, from the personalized medicine enabled by genomics, these advances have served to create bigger gaps between scientific advance and commercial reality, demanding deeper understanding of the science.
The rapid pace of technology development across all these sectors and the increasing complexity of the underlying science are factors complicating the development, regulatory approval, and market introduction of advanced technologies. The unexpected size and number of the hurdles to bring these complex technologies to the market have been responsible for investment failures, such as:
Theranos. Investors were too ready to believe the disruptive ideas of its founder, Elizabeth Holmes. When it became clear that data did not support the technology, the value of the company plummeted.
Juno Therapeutics. The Seattle-based gene therapy company lost substantial share value after three patients died on a clinical trial for the company’s cell therapy treatments that were just months away from receiving regulatory approval in the US.
A ZS Associates study in 2016 showed that 81% of medtech companies struggle to receive an adequate return on investment
As a result, investment in biotech took a correctional hit in 2016 to deflate overblown expectations. Medtech, for its part, has seen declining investment, especially at early stages, reflecting an aversion to uncertainty in commercialization.
Below are clinical and technology areas that we see demonstrating growth and investment opportunity, but still represent challenges for executives to navigate their remaining development and commercialization obstacles:
Type I diabetes
Non-invasive blood glucose measurement
Tissue engineering and regeneration
3D printed organs
Brain-computer and other nervous system interfaces
Interfaces for patients with locked-in syndrome to communicate
Interfaces to enable (e.g., Stentrode) paralyzed patients to control devices
Robotics in surgery (advancing, despite costs)
Optogenetics: light modulated nerve cells and neural circuits
Localized drug delivery
Further accelerated by genomics and computational approaches
Computational approaches to accelerate the evaluation of drug candidates
Organ-on-a-chip technologies to decrease the cost of drug testing
Impact on investment
Seed stage and Series A investment in med tech is down, reflecting an aversion to early stage uncertainty.
Acquisitions of early stage companies, by contrast, are up, reflecting acquiring companies to gain more control over the uncertainty
Need for critical insight and data to ensure patient outcomes at best costs
Costs of development, combined with uncertainty, demand that if the idea’s upside potential is only $10 million, then it’s time to find another idea
While better analysis of the hurdles to commercialization of advanced innovations will support investment, many medtech and biotech companies may opt instead for growth of established technologies into emerging markets, where the uncertainty is not science-based
Below is illustrated the fundings by category in 2015 and 2016, which showed a consistent drop from 2015 to 2016, driven by a widely acknowledged correction in biotech investment in 2016.
*For the sake of comparing other segments, the wound fundings above exclude the $1.8 billion IPO of Convatec in 2016.
Due to the uncertainty in the development, clinical testing, and regulatory approval of both biotech and medical technologies, which increasingly have to be viewed with the same competitive lens, investors have over the past few years shied away from seed stage or Series A stage company investment in favor of those nearer to market introduction. However, with the advent of a great number of new technologies and advances in the underlying science, there is enormous opportunity to identify companies and emerging sectors arising from these advances. The problem in identifying realistically promising companies is that it must be done so without falling prey to the bad investment practices in the past that ensued from a poor understanding of the technologies and their remaining commercial hurdles. Without careful consideration of remaining scientific development needed, the product’s target market, its competitors, and the sum total of the company’s capabilities to commercialize these technologies, investment in these areas will fall short of investment objectives or fail them outright.
While any of these considerations have the capacity to preempt a successful market introduction, a failure to understand the science behind the product and its remaining development hurdles to commercialization is likely to be the biggest cause of failure.
“We’ve already had one glaring example of a company, and its investors, learning the hard way that health and science advisors are important: Theranos.” (link)
Venture Capital has backed away from early stage investment
Earlier stage investment, with its higher risk, has higher potential reward, so there is a big need for more effective evaluation of potential early stage investments in order to (1) seize these opportunities that will otherwise potentially be lost with the shift to later stage fundings, (2) sort out those companies/technologies with overwhelming commercialization hurdles from those that will profitably tap an opportunity, and (3) gain the value of these opportunities before the innovation appreciates in value, driving up the price of the investment.
The Biotech Bubble
Biotech in the 1980s was enamored with companies pursuing “magic bullets” — technologies that had the potential to cure cancer or heart disease or other conditions with large, untapped or under-treated populations. With few exceptions, these all-in-one-basket efforts were only able achieve a measure of humility in the VCs who had poured volumes of money into them.
Here was evidenced a fundamental problem with biotech at a time when true scientific milestones were being reached, including successes in mapping the human genome: Landmark scientific milestones do not equate with commercial success.
As a result, money fled from biotech as few products could make it to market due to persistent development and FDA hurdles. By the late 1980s, many biotechs saw three quarters of their value disappear.
A Renewed Bubble?
The status of biomedical science and technology, with multiple synergistic developments, will lead to wild speculation and investment, potentially leading to yet another investment bubble. However, there will be advances that can point to real timelines for market introduction that will support investment.
Recent advances, developments and trends supporting emerging therapeutics
Stem cells. A double-edged sword in that these do represent some the biggest therapeutics that will emerge, yet caution is advised since the mechanisms to control stem cells are not always sufficient to prevent their nasty tendency to become carcinogenic.
Drug discovery models, such as using human “organoids” and other cell-based models to test or screen new drugs.
Systems to accelerate the rapid evaluation of hundreds, perhaps, thousands of potential drugs before moving to animal models or preclinicals.
Meta-analysis, the practice of analyzing multiple, independently produced clinical data to draw conclusions from the broader dataset.
cell biologists, immunologists, molecular biologists and others have a better understanding of pathology and therapeutics as a result of information sharing; plus BIG DATA (e.g., as part of the “Cancer Moonshot”). Thought leaders have called for collection and harnessing of patient data on a large scale and centralized for use in evaluating treatments for specific patients and cancer types.
Artificial intelligence applied to diagnosis and prescribed therapeutics (e.g., IBM Watson).
Examples of resulting therapies, at a minimum, include multimodal treatment – e.g., radiotherapy and immunotherapy – but more often may be represented in considerably more backend research and testing to identify and develop products with greater specificity, greater efficacy, and lowered risk of complications.
In reviewing patents, fundings, technology development trends, market development, and other hard data sources, we feel these are some of the strongest areas for investment in not only the medical device side of medtech, but also the broader biomedical technology arena:
Cancer probes (e.g., fluorescent or optical coherence tomography, frozen section, cytologic imprint analysis, ultrasound, micro-computed tomography, near-infrared imaging, and spectroscopy)
neurostimulation and neuromodulation
In addition, there are many areas in healthcare in which there is much untapped demand with problems that, so far, seem to have eluded medtech solutions. These include infection control (Zika, MRSA, TB, nosocomial infections, etc.), chronic wound treatment (including decubitus/stasis/diabetic ulcers), type 2 diabetes and obesity.
The market for wound management products — as varied as negative pressure wound therapy, skin grafts, hydrogel dressings, and growth factors — is a sort of free-for-all of offerings designed to accelerate healing, reduce treatment costs, yield better outcomes, or all of these and more. With so many sectors, and with well-established ones tending toward commodity, there can be many competitors, with few having significant market shares. Yet in several areas, quite remarkable growth is still available. Excluding traditional bandage and dressings, three companies — S&N, Acelity and Mölnlycke — control over half the worldwide market.
The MedMarket Diligence report #S251, “Worldwide Wound Management, Forecast to 2024: Established and Emerging Products, Technologies and Markets in the Americas, Europe, Asia/Pacific and Rest of World,” is detailed at link and is available for purchase and download online.
Sales of sealants, glues, and hemostats projected to 2022 for the U.S. and Asia/Pacific. While these products have had tremendous success in Japan, their sales in the rest of Asia/Pacific have not yet caught up to Japan, let alone to the U.S.
But that is expected to change as the most significant growth in these markets will indeed be coming from China, Korea, Australia, India, and elsewhere in these emerging markets.
Sales of Sealants, Glues, and Hemostats in the U.S. and Asia/Pacific Markets, 2015-2022
Note: For direct comparative purposes, sales in these markets are shown on the same vertical scale.
There are several different classes of surgical sealants, glues and hemostatic products used to prevent or stop bleeding, or to close a wound or reinforce a suture line. These include fibrin sealants, surgical sealants, mechanical hemostats, active hemostats, flowable hemostats, and glues. Both sealants and medical glues are increasingly used either as an adjunct to sutures or to replace sutures.
Fibrin sealants are made of a combination of thrombin and fibrinogen. These sealants may be sprayed on the bleeding surface, or applied using a patch. Surgical sealants might be made of glutaraldehyde and bovine serum albumin, polyethylene glycol polymers, and cyanoacrylates.
Sealants are most often used to stop bleeding over a large area. If the surgeon wishes to fasten down a flap without using sutures, or in addition to using sutures, then the product used is usually a medical glue.
The surgeon and the perioperative nurse have a variety of hemostats from which to choose, as they are not all alike in their applications and efficacy. Selection of the most appropriate hemostat requires training and experience, and can affect the clinical outcome, as well as decrease treatment costs. Some of the factors that enter into the decision-making process include the size of the wound, the amount of hemorrhaging, potential adverse effects, whether the procedure is MIS or open surgery, and others.
Active hemostats contain thrombin products which may be derived from several sources, such as bovine pooled plasma purification, human pooled plasma purification, or through human recombinant manufacturing processes. Flowable-type hemostats are made of a granular bovine or porcine gelatin that is combined with saline or reconstituted thrombin, forming a flowable putty that may be applied to the bleeding area. Mechanical hemostats, such as absorbable gelatin sponge, collagen, cellulose, or polysaccharide-based hemostats applied as sponges, fleeces, bandages, or microspheres, are not included in this analysis.
Sealants and glues are terms which are often used interchangeably, which can be confusing. In this report, a medical glue is defined as a product used to bond two surfaces together securely. Surgeons are increasingly reaching for medical glues to either help secure a suture line, or to replace sutures entirely in the repair of soft tissues. Medical glues are also utilized in repairing bone fractures, especially for highly comminuted fractures that often involve many small fragments. This helps to spread out the force-bearing surface, rather than focusing weight-bearing on spots where a pin has been inserted.
Thus, the surgeon has a fairly wide array of products from which to choose. The choice of which surgical hemostat or sealant to use depends on several factors, including the procedure being conducted, the type of bleeding, severity of the hemorrhage, the surgeon’s experience with the products, the surgeon’s preference, the price of the product and availability at the time of surgery. For example, a product which has a long shelf life and does not require refrigeration or other special storage, and which requires no special preparation, usually holds advantages over a product which must be mixed before use, or held in a refrigerator during storage, then allowed to warm up to room temperature before use.
Hemostat sales are exceptionally strong in the well developed economies (Japan, Australia, Korea) of Asia, and will continue to expand there with the rapidly growing contribution of China’s hemostat sales.
The fastest growth in the sales of surgical sealants over the next decade will be in the Asia-Pacific region, driven primarily by very strong healthcare market growth in China, and reaching a CAGR (2016-2022) of at least 13.97%. The growth rate in China would be even higher, but will be dampened for the time being by the lack of surgeons trained in the proper use of these products, as well as the limitations of reaching a dispersed patient population. Nonetheless, the A/P share of the global sealants market will double in the next seven years!
Below illustrates the geographic distribution of surgical sealants (fibrin and others) in 2015.
Regional Markets for Sealants, Fibrin and Other Sealant Products, 2015 & 2022, USD Millions