Forgotten Opportunities: Early Stage Biotech and Medtech Investment

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

  1. 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.
  2. Drug discovery models, such as using human “organoids” and other cell-based models to test or screen new drugs.
  3. Systems to accelerate the rapid evaluation of hundreds, perhaps, thousands of potential drugs before moving to animal models or preclinicals.
    1. Machine-learning algorithms
    2. Cell/tissue/organ models
    3. Meta-analysis, the practice of analyzing multiple, independently produced clinical data to draw conclusions from the broader dataset.
  4. Cross-discipline science
    1. 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.
    2. Artificial intelligence applied to diagnosis and prescribed therapeutics (e.g., IBM Watson).
    3. 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.
  5. Materials science developments, selected examples:
    1. Scaffolds in tissue engineering
    2. Microgels
    3. Graphene
    4. Polyhedral boranes
    5. Nanometric imprinting on fiber
    6. Knitted muscles to provide power link
    7. 3-D printed skin and more complex organs to come
    8. Orthopedic scaffolds made from electrospun nanofibers
  6. CAR-T (chimeric antigen receptor T cell therapy)
  7. CRISPR/Cas-9. Gene editing
    1. Removal, insertion of individual genes responsible for disease
    2. Potential use for creating chimeras of human and other (e.g., pig) species in order to, for example, use pigs for growing human organs for transplant.
  8. Smart devices: smart biopsy needles, surgical probes to detect cancer margins, artificial pancreas. Devices using information

 

We sum this up with these prerequisites for investment:

Prerequisites for Early Stage Med/Bio Investment

  1. A fully understood and managed gap between scientific advance and commercial reality.
    1. Investment must be tied to specific steps (prototyping, preclinicals, clinicals, physician training, etc.).
  2. A management team qualified in commercializing medtech or biotech products.
    1. CEOs (and/or Chief Medical Officers, Chief Scientific Officers) with medical science backgrounds (MD, PhD) favored over CPAs or even JDs.
  3. Reimbursement strategy pursued as something more than an afterthought
  4. Technology development in sync with end-user acceptance and training to leverage the benefits:
    1. Easier to use
    2. Fewer complications
    3. Attractive physician revenue streams
  5. Broad competitive advantage pursued:
    1. Product benefits must stand up against all competition, irrespective of technology type (devices competing with drugs, biotech).
    2. Benefits of reducing the cost of care for an existing patient population are paramount.
    3. Competitive advantage must consider the trend in technology development to avoid being disrupted by other products soon to reach the market.
  6. Predefined exit strategy; selected examples:
    1. Positioning to add innovation to a mid-cap or large-cap medtech or biotech as acquirers.
    2. Development of platform technologies for licensing or sale.
    3. IPO

 

Future investments are likely to track the historical focus on specific diseases and conditions:

Source: MedMarket Diligence, LLC and Emerging Therapeutic Company Investment and Deal Trends; Biotechnology Innovation Organization.


MedMarket Diligence, mediligence.com, tracks medical and biotechnology development to provide meaningful insights for manufacturers, investors, and other stakeholders.

The best medtech investment opportunities

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:

  • Materials technologies
    • graphene
    • bioresorbables
    • biosensors
    • polymers
    • bioadhesives
  • Cell therapy and tissue engineering
    • cell-based treatments (diabetes, spinal cord injury, traumatic brain injury)
    • extracellular matrices in soft tissue repair and regeneration
  • Nanotechnology (subject of forthcoming report)
    • nano coatings
    • nano- and micromedical technologies for localized drug delivery
    • nanoparticles
  • 3D printing
    • prototype development
    • patient-specific implants
  • Minimally- and non-invasive technologies
    • transcatheter alternatives to surgery
    • NOTES (natural orifice transluminal endoscopic surgery)
  • Diabetes non-invasive glucose testing
  • Intraoperative surgical guidance
    • 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
  • point-of-care diagnostics
  • point-of-care imaging
  • AI-enhanced devices

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.

 

Market fragmentation and growth, decline in wound management

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.

Global Advanced Wound Market Market Shares

Source: MedMarket Diligence, LLC; Report #S251. Order online.

Growth is coming in the advanced areas of bioengineered skin, the ever-needed antimicrobials, and the great demand for foam dressings.


Source: MedMarket Diligence, LLC; Report #S251. Order online.

 

Viewed another way, with size and growth mapped relative to each other…

 

Source: MedMarket Diligence, LLC; Report #S251. Order online.

The U.S. remains the biggest consumer of wound management products, and this is not expected to materially change. Europe is seeing relative decline, however, as Asia Pacific demand ramps up:

Source: MedMarket Diligence, LLC; Report #S251. Order online.


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

Wound closure and healing via sealants, glues, hemostats in development

Natural tissue healing is a highly complex dance of processes that need to be working properly in order for the body to heal. Mammals have developed the ability to heal wounds rapidly through a cascade of processes that starts with hemostasis (blood clotting) to slow or stop the loss of blood. From the moment of injury, platelets start to aggregate, as well as starting to release cytokines, chemokines and hormones. Vasoconstriction takes place as the body tries to limit the loss of blood, and several vasoactive mediators come into play, including, norepinephrine, epinephrine, prostaglandins, serotonin, and thromboxane. Activated platelets lead to formation of a clot. Next, the inflammatory steps kick in, targeting and killing microbes and launching a natural internal debridement process, which serves to clean up any damaged tissue so that reconstruction may occur. Last in the cascade are the proliferative and maturation phases. These involve the deposition of new tissue matrix materials, and are intended to lead to reconstruction of tissue organelles and cellular structure. These healing steps actually overlap one another, and do not have strict times when each process begins or ends.

A delicate physiological balance must be maintained during the healing process to ensure timely repair or regeneration of damaged tissue. Wounds may fail to heal or have a greatly increased healing time when unfavorable conditions are allowed to persist. An optimal environment must be provided to support the essential biochemical and cellular activities required for efficient wound healing and to remove or protect the wound from factors that impede the healing process.

Factors affecting wound healing may be considered in one of two categories depending on their source. Extrinsic factors impinge on the patient from the external environment, whereas intrinsic factors directly affect the performance of bodily functions through the patient’s own physiology or condition. Factors which strongly affect wound healing include smoking, diabetes, age, oxygenation, stress, obesity, certain medications, alcoholism and nutrition.

Timescales for Development of
Sealants, Glues and Hemostat Products

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Source: MedMarket Diligence, LLC; Report #S290.

While product development continues apace, and companies are launching their products in new countries, launches of actual new products has been relatively slow. This is due most likely to the highly technical (read: expensive) nature of the product development, as well as the cost and time involved in running clinical trials, and the strong patent protection which has been erected, especially by the leading companies. The need for the products is there, but the required clinical testing is putting a brake on the markets.

In July 2015, HyperBranch announced the product launch of Adherus® AutoSpray Dural Sealant in the US. FDA clearance to market the product was obtained in March 2015. The absorbable sealant is intended for use in brain surgery and is applied over the sutures for dura repair to prevent cerebrospinal fluid from leaking out of the incision site. The Adherus® AutoSpray Dural Sealant is made of two solutions: a PEG ester solution and a polyethylenimine (PEI) solution. When mixed together, the solutions combine to form a sealant gel that is applied to the incision site. According to the company, the sealant is fully absorbed in about 90 days.

Cohera Medical launched its TissuGlu® in select US cities in November 2015. At this point, TissuGlu® is available in ten cities in the USA, while B. Braun is the distributor for the product in Germany, Spain and Portugal.

Sanyo Chemical launched its first medical device, Hydrofit, in February 2014. The company obtained the approval of the medical device under the Pharmaceutical Affairs Law in December 2011, filing it as a novel surgical hemostatic agent intended for anastomosing the arterial blood and artificial blood vessel in surgical procedures. According to the company, the product will be produced by Sanyo and marketed by Terumo.

In 2014, Cohera Medical, Inc. launched Sylys Surgical Sealant, which can be used in gastrointestinal surgery to decrease anastomotic leak. In the same year, Baxter also gained the FDA permission for Tisseel® fibrin sealant, which, according to the company, is used in almost all types of surgical procedures.

Mallinckrodt will invest in the commercial launch and ongoing market development of both PreveLeak and Raplixa in FY 2016. According to the company, both products are faster to prepare and easier to use and store than competing products. PreveLeak, a surgical sealant, is allegedly more flexible than hemostasis glue products. It is indicated for use in vascular reconstructions to achieve adjunctive hemostasis by sealing areas of leakage. PreveLeak is currently marketed in Europe through distributors.

In an example of a delayed launch, CryoLife has been working towards launch of PerClot in the US, but ran into litigation trouble with Medafor, a wholly-owned subsidiary of CR Bard. In November 2015, CryoLife announced that it had entered into a resolution with Medafor to end the patent dispute in the US District Court for the District of Delaware between the companies regarding PerClot. Under terms of the resolution, all parties agreed to end the litigation, jointly dismissing all claims and counterclaims with prejudice and waiving all appeal rights in this case.  Each party is to pay its own attorneys’ fees and costs associated with the litigation.  However, the court’s preliminary injunction entered March 31, 2015 with respect to CryoLife’s marketing and sale of PerClot in the US will remain in effect until the expiration of Medafor’s US Patent No. 6,060,461 (the “‘461 Patent”) on February 8, 2019. CryoLife management says that this will not upset their plans, as CryoLife does not expect to receive FDA market approval for PerClot before 2018, if then.


From “Sealants, Glues, Hemostats to 2022” (#S290).

The Regimens for Assessing and Treating Wound Types

Wound treatment starts with diagnosis. Acute wounds are often surgically created, or dealt with in accident and emergency (A&E) settings. Diagnosis in the acute scenario usually focuses on cleanliness and tidying of the wound edges to enable securement using sutures or glue products. If major trauma has occurred, hemostats and sealants may be required. In the chronic scenario, diagnosis is a process that occurs at every treatment session. The practitioner will examine size, appearance and odor changes to the wound, and from this process determine the ideal management. In addition, it is likely that the physician will take samples to send for microbial assessment if infection becomes a concern.

Following diagnosis and assessment, treatment will be established based on known efficacy and cost of individual dressings, knowledge of the potential products that may be used, and their availability. This will be determined by reimbursement, local purchasing decisions, and resources.

For chronic wounds, treatment often involves symptoms; many products are designed to remove aesthetically unpleasant aspects of wounds such as exudates, smell, and visibility.

Management of exudates also has a wound-healing benefit. Too much exudate leads to hydrolytic damage and maceration of the tissue and surrounding skin. Too little moisture leads to drying out of the wound and cell death. As a result, many advanced wound management products have been developed to optimize the moist wound healing environment. As a huge variety of wound conditions arise, a large number of dressings has been developed to help manage the full range of circumstances that may be encountered. These include dressings made from foams, polyurethane films, alginates, hydrocolloids, and biomaterials to manage exudates, which may be present in vast quantities (perhaps as much as two liters per square meter per day). Other products are designed to moisten the wound to optimize healing (amorphous hydrogels for example).

Much of the advanced wound management market has evolved to improve exudates management in the home setting, in order to reduce the need for visits by practitioners and the associated cost.

Types and Uses of Select Wound Care Products

    
Dressing categoryProduct examplesDescriptionPotential applications
FilmHydrofilm, Release, Tegaderm, BioclusiveComes as adhesive, thin transparent polyurethane film, and as a dressing with a low adherent pad attached to the film.Clean, dry wounds, minimal exudate; also used to cover and secure underlying absorptive dressing, and on hard-to-bandage locations, such as heel.
FoamPermaFoam
PolyMem
Biatain
Polyurethane foam dressing available in sheets or in cavity filling shapes. Some foam dressing have a semipermeable, waterproof layer as the outer layer of the dressingFacilitates a moist wound environment for healing. Used to clean granulating wounds which have minimal exudate.
HydrogelHydrosorb Gel Sheet, Purilon, Aquasorb, DuoDerm, Intrasite Gel, GranugelColloids which consist of polymers that expand in water. Available in gels, sheets, hydrogel-impregnated dressings.Provides moist wound environment for cell migration, reduces pain, helps to rehydrate eschar. Used on dry, sloughy or necrotic wounds.
HydrocolloidCombiDERM, Hydrocoll, Comfeel, DuoDerm CGF Extra Thin, Granuflex, Tegasorb, Nu-DermMade of hydroactive or hydrophilic particles attached to a hydrophobic polymer. The hydrophilic particles absorb moisture from the wound, convert it to a gel at the interface with the wound. Conforms to wound surface; waterproof and bacteria proof.Gel formation at wound interface provides moist wound environment. Dry necrotic wounds, or for wounds with minimal exudate. Also used for granulating wounds.
AlginateAlgiSite, Sorbalgon Curasorb, Kaltogel, Kaltostat, SeaSorb, TegagelA natural polysaccharide derived from seaweed; available in a range of sizes, as well as in ribbons and ropes.Because highly absorbent, used for wounds with copious exudate. Can be used in rope form for packing exudative wound cavities or sinus tracts.
AntimicrobialBiatain Ag
Atrauman Ag
MediHoney
Both silver and honey are used as antimicrobial elements in dressings.Silver: Requires wound to be moderately exudative to activate the silver, in order to be effective
NPWDSNa
V.A.C. Ulta
PICO
Renasys (not in USA)
Prospera PRO series
Invia Liberty
Computerized vacuum device applies continuous or intermittent negative or sub-atmospheric pressure to the wound surface. NPWT accelerates wound healing, reduces time to wound closure. Comes in both stationary and portable versions.May be used for traumatic acute wound, open amputations, open abdomen, etc. Seems to increase burn wound perfusion. Also used in management of DFUs. Contraindicated for arterial insufficiency ulcers. Not to be used if necrotic tissue is present in over 30% of the wound.
Bioengineered Skin and Skin SubstitutesAlloDerm, AlloMax, FlexHD, DermACELL, DermaMatrix, DermaPure, Graftjacket Regenerative Tissue Matrix, PriMatrix, SurgiMend PRS, Strattice Reconstructive Tissue Matrix, Permacol, EpiFix, OASIS Wound Matrix, Apligraf, Dermagraft, Integra Dermal Regeneration Template, TransCyteBio-engineered skin and soft tissue substitutes may be derived from human tissue (autologous or allogeneic), xenographic, synthetic materials, or a composite of these materials.Burns, trauma wounds, DFUs, VLUs, pressure ulcers, postsurgical breast reconstruction, bullous diseases

Source: MedMarket Diligence, LLC; Report #S251.

In some cases, the wound may be covered by a black necrotic tissue or yellow sloughy material. These materials develop from dead cells, nucleic acid materials, and denatured proteins. In order for new tissue to be laid down, this dead material needs to be removed. It may be done using hydrolytic debridement using hydrogels that soften the necrotic tissue, or by the use of enzymes. Surgical debridement is another option, but non-surgical debridement has the advantage that it is usually less painful and can be performed with fewer materials, less expertise, and less mess. It is possible to perform non-surgical debridement in the home setting. Debridement can also be performed to selectively remove dead tissue and thus encourage repair. Enzymatic debriders have been able to command a premium price in the market, and built a sizeable share of the wound management market, particularly during the 1990s when treatment in the home environment increased as a result of reductions in hospital-based treatment. These products are described in the section on cleansers and debriders.

Occasionally healthcare practitioners put maggots to work for wound debridement. Though esthetically unpleasant, maggots are very effective debriding agents because they distinguish rigorously between dead and living tissue. Military surgeons noticed the beneficial effect of maggots on soldiers’ wounds centuries ago, but maggot debridement therapy (MDT) as it is practiced today began in the 1920s and has lately been undergoing something of a revival. The maggots used have been disinfected during the egg stage so that they do not carry bacteria into the wound. The larvae preferentially consume dead tissue, they excrete an antibacterial agent, and they stimulate wound healing.

At the other end of the technological scale are skin substitutes, which have been developed to help in the management of extensive wounds such as burns. Autologous skin grafting is a well-established therapeutic technique; postage-stamp-sized sections of healthy skin are cultured and grown in vitro, then placed over the raw wound surface to serve as a focus for re-epithelialization. However, this process takes time; the wound is highly vulnerable to infection while the skin graft is being grown. A number of companies have developed alternatives in the form of synthetic skin substitutes. These are described further in the next section of the report.

A number of products have also been developed to deal with sloughy and infected wounds. These often incorporate antimicrobial agents. Often, infected wounds have a very unpleasant odor; a range of odor control dressings has arisen to deal with this.

Once wounds begin to heal, the amount of exudate starts to decrease. Some dressing products preserve moisture but are also non-adhesive, so that the dressing does not adhere to the new epithelializing skin. These products are called non-adherent dressings and include a range of tulle dressings, which usually consist of a loose weave of non-adherent fabric designed to allow exudates to pass through the gaps. A subgroup of dressings is designed to keep the skin moist in order to reduce scarring after healing.

For wounds that do not appear to be healing, a number of companies have explored the potential to add growth factors and cells to promote and maintain healing. In addition, companies have attempted to use energy sources to accelerate wound healing, and these are described in the section on physical treatments. The main example of physical treatment is the use of devices which apply negative pressure over the wound and have been shown to dramatically shorten the healing of diabetic ulcers and other chronic wounds.

Often, a dressing will serve more than one purpose. Therefore, it is difficult to generalize and collect only dressings that serve one purpose into a single category. For example, Systagenix’s Actisorb Plus (Systagenix is now owned by Acelity) is a woven, low-adherent odor control antimicrobial dressing designed to optimize moist wound healing through its exudates handling properties.


From, Worldwide Wound Management, Forecast to 2024; MedMarket Diligence, LLC. 

Wound management practice patterns, products by wound type

From Report #S251, “Wound Management to 2024”.

Surgical wounds account for the vast majority of skin injuries. We estimate that there are approximately 100 million surgical incisions per year, growing at 3.1% CAGR, that require some wound management treatment. About 16 million operative procedures were performed in acute care hospitals in the USA. Approximately 80% of surgical incisions use some form of closure product: sutures, staples, and tapes. Many employ hemostasis products, and use fabric bandages and surgical dressings.

Surgical procedures generate a preponderance of acute wounds with uneventful healing and a lower number of chronic wounds, such as those generated by wound dehiscence or postoperative infection. Surgical wounds are most often closed by primary intention, where the two sides across the incision line are brought close and mechanically held together. Overall the severity and size of surgical wounds will continue to decrease as a result of the continuing trend toward minimally invasive surgery.

Surgical wounds that involve substantial tissue loss or may be infected are allowed to heal by secondary intention where the wound is left open under dressings and allowed to fill by granulation and close by epithelialization. Some surgical wounds may be closed through delayed primary intention where they are left open until such time as it is felt it is safe to suture or glue the wound closed.

Traumatic wounds occur at the rate of 50 million or more every year worldwide. They require cleansing and treatment with low-adherent dressings to cover the wound, prevent infection, and allow healing by primary intention. Lacerations are a specific type of trauma wound that are generally minor in nature and require cleansing and dressing for a shorter period. There are approximately 20 million lacerations a year as a result of cuts and grazes; they can usually be treated in the doctors’ surgery, outpatient medical center or hospital A&E departments.

Burn wounds can be divided into minor burns, medically treated, and hospitalized cases. Outpatient burn wounds are often treated at home, at the doctor’s surgery, or at outpatient clinics. As a result, a large number of these wounds never enter the formal health service system. According to the World Health Organization (WHO), globally about 11 million people are burned each year severely enough to require medical treatment. We estimate that approximately 3.5 million burns in this category do enter the outpatient health service system and receive some level of medical attention. In countries with more developed medical systems, these burns are treated using hydrogels and advanced wound care products, and they may even be treated with consumer-based products for wound healing.

Medically treated burn wounds usually receive more informed care to remove heat from the tissue, maintain hydration, and prevent infection. Advanced wound care products are used for these wounds. There are approximately 6.0 million burns such as this that are treated medically every year.

Hospitalized burn wounds are rarer and require more advanced and expensive care. These victims require significant care, nutrition, debridement, tissue grafting and often tissue engineering where available. They also require significant follow-up care and rehabilitation to mobilize new tissue, and physiotherapy to address changes in physiology. Growth rates within the burns categories are approximately 1.0% per annum.

Chronic wounds generally take longer to heal, and care is enormously variable, as is the time to heal. There are approximately 7.4 million pressure ulcers in the world that require treatment every year. Many chronic wounds around the world are treated sub-optimally with general wound care products designed to cover and absorb some exudates. The optimal treatment for these wounds is to receive advanced wound management products and appropriate care to address the underlying defect that has caused the chronic wound; in the case of pressure ulcers a number of advanced devices exist to reduce pressure for patients. There are approximately 9.7 million venous ulcers, and approximately 10.0 million diabetic ulcers in the world requiring treatment. Chronic wounds are growing in incidence due to the growing age of the population, and the growth is also due to increasing awareness and improved diagnosis. Growth rates for pressure and venous ulcers are 6%–7% in the developed world as a result of these factors.

Diabetic ulcers are growing more rapidly due mainly to increased incidence of both Type I and maturity-onset diabetes in the developed countries around the world. The prevalence of diabetic ulcers is rising at 9% annually. Every year 5% of diabetics develop foot ulcers and 1% require amputation. The recurrence rate of diabetic foot ulcers is 66%; the amputation rate rises to 12% with subsequent ulcerations. At present, this pool of patients is growing faster than the new technologies are reducing the incidence of wounds by healing them.

Wound management products are also used for a number of other conditions including amputations, carcinomas, melanomas, and other complicated skin cancers, all of which are on the increase.

A significant feature of all wounds is the likelihood of pathological infection occurring. Surgical wounds are no exception, and average levels of infection of surgical wounds are in the range of 7%–10%, depending upon the procedure. These infections can be prevented by appropriate cleanliness, surgical discipline and skill, wound care therapy, and antibiotic prophylaxis. Infections usually lead to more extensive wound care time, the use of more expensive products and drugs, significantly increased therapist time, and increased morbidity and rehabilitation time. A large number of wounds will also be sutured to accelerate closure, and a proportion of these will undergo dehiscence and require aftercare for healing to occur.

For the detailed coverage of wounds, wound management products, companies, and markets, see report #S251, “Worldwide Wound Management to 2024”.

List of high growth medtech products

Below is a table with a list of the market segments demonstrating greater than 10% compound annual growth rate for the associated region through 2022, drawn from our reports on tissue engineering & cell therapy, wound management, ablation technologies, stroke, peripheral stents, and sealants/glues/hemostats. Products with over 10% CAGR in sales are shown in descending order of CAGR.

RankProductTopicRegion
1General, gastrointestinal, ob/gyn, othertissue/cellWW
2Ophthalmologytissue/cellWW
3Organ Replacement/ Repairtissue/cellWW
4Urologicaltissue/cellWW
5Neurologicaltissue/cellWW
6Autoimmune Diseasestissue/cellWW
7CV/ Vasculartissue/cellWW
8Bioengineered skin and skin substituteswoundRest of A/P
9Peripheral drug-eluting stents (A/P)peripheral interventionalA/P
10Peripheral drug eluting stentsperipheral interventionalRoW
11Peripheral drug-eluting stents (US)peripheral interventionalUS
12Negative pressure wound therapywoundGermany
13Hydrocolloid dressingswoundRest of A/P
14Cancertissue/cellWW
15Foam dressingswoundRest of A/P
16Growth factorswoundRest of A/P
17Alginate dressingswoundRest of A/P
18Dentaltissue/cellWW
19Bioengineered skin and skin substituteswoundJapan
20Hemostatssealants, glues, hemostatsA/P
21Skin/ Integumentarytissue/cellWW
22Bioengineered skin and skin substitutessealants, glues, hemostatsUS
23Bioengineered skin and skin substitutessealants, glues, hemostatsWW
24Film dressingswoundRest of A/P
25Surgical sealantssealants, glues, hemostatsA/P
26Hydrogel dressingswoundRest of A/P
27TAA Stent graftsperipheral interventionalA/P
28Negative pressure wound therapywoundRoW
29Biological gluessealants, glues, hemostatsA/P
30FoamwoundRoW
31HydrocolloidwoundGermany
32AAA Stent graftsperipheral interventionalA/P
33Cerebral thrombectomy systemsstrokeA/P
34High-strength medical gluessealants, glues, hemostatsA/P
35Carotid artery stenting systemsstrokeA/P
36Cardiac RF ablation productsablationA/P
37Alginate dressingswoundGermany
38Peripheral venous stentsperipheral interventionalA/P
39Cerebral thrombectomy systemsstrokeUS
40Left atrial appendage closure systemsstrokeA/P
41Cyanoacrylate gluessealants, glues, hemostatsA/P
42Foam dressingswoundRest of EU
43Foam dressingswoundKorea
44Cryoablation cardiac & vascular productsablationA/P
45Bioengineered skin and skin substituteswoundGermany
46Thrombin, collagen & gelatin-based sealantssealants, glues, hemostatsA/P
47Cardiac RF ablation productsablationRoW
48Bioengineered skin and skin substituteswoundRoW
49Microwave oncologic ablation productsablationA/P

Note source links: Tissue/Cell, Wound, Sealants/Glues/Hemostats, Peripheral Stents, Stroke, Ablation.

Source: MedMarket Diligence Reports

Where will medicine be in 2035?

An important determinant of “where medicine will be” in 2035 is the set of dynamics and forces behind healthcare delivery systems, including primarily the payment method, especially regarding reimbursement. It is clear that some form of reform in healthcare will result in a consolidation of the infrastructure paying for and managing patient populations. The infrastructure is bloated and expensive, unnecessarily adding to costs that neither the federal government nor individuals can sustain. This is not to say that I predict movement to a single payer system — that is just one perceived solution to the problem. There are far too many costs in healthcare that offer no benefits in terms of quality; indeed, such costs are a true impediment to quality. Funds that go to infrastructure (insurance companies and other intermediaries) and the demands they put on healthcare delivery work directly against quality of care. So, in the U.S., whether Obamacare persists (most likely) or is replaced with a single payer system, state administered healthcare (exchanges) or some other as-yet-unidentified form, there will be change in how healthcare is delivered from a cost/management perspective. 

From the clinical practice and technology side, there will be enormous changes to healthcare. Here are examples of what I see from tracking trends in clinical practice and medical technology development:

  • Cancer 5 year survival rates will, for many cancers, be well over 90%. Cancer will largely be transformed in most cases to chronic disease that can be effectively managed by surgery, immunology, chemotherapy and other interventions. Cancer and genomics, in particular, has been a lucrative study (see The Cancer Genome Atlas). Immunotherapy developments are also expected to be part of many oncology solutions. Cancer has been a tenacious foe, and remains one we will be fighting for a long time, but the fight will have changed from virtually incapacitating the patient to following protocols that keep cancer in check, if not cure/prevent it. 
  • Diabetes Type 1 (juvenile onset) will be managed in most patients by an “artificial pancreas”, a closed loop glucometer and insulin pump that will self-regulate blood glucose levels. OR, stem cell or other cell therapies may well achieve success in restoring normal insulin production and glucose metabolism in Type 1 patients. The odds are better that a practical, affordable artificial pancreas will developed than stem or other cell therapy, but both technologies are moving aggressively and will gain dramatic successes within 20 years.

Developments in the field of the “artificial pancreas” have recently gathered considerable pace, such that, by 2035, type 1 blood glucose management may be no more onerous than a house thermostat due to the sophistication and ease-of-use made possible with the closed loop, biofeedback capabilities of the integrated glucometer, insulin pump and the algorithms that drive it, but that will not be the end of the development of better options for type 1 diabetics. Cell therapy for type 1 diabetes, which may be readily achieved by one or more of a wide variety of cellular approaches and product forms (including cell/device hybrids) may well have progressed by 2035 to become another viable alternative for type 1 diabetics.

  • Diabetes Type 2 (adult onset) will be a significant problem governed by different dynamics than Type 1. A large body of evidence will exist that shows dramatically reduced incidence of Type 2 associated with obesity management (gastric bypass, satiety drugs, etc.) that will mitigate the growing prevalence of Type 2, but research into pharmacologic or other therapies may at best achieve only modest advances. The problem will reside in the complexity of different Type 2 manifestation, the late onset of the condition in patients who are resistant to the necessary changes in lifestyle and the global epidemic that will challenge dissemination of new technologies and clinical practices to third world populations.

Despite increasing levels of attention being raised to the burden of type 2 worldwide, including all its sequellae (vascular, retinal, kidney and other diseases), the pace of growth globally in type 2 is still such that it will represent a problem and target for pharma, biotech, medical device, and other disciplines.

  • Cell therapy and tissue engineering will offer an enormous number of solutions for conditions currently treated inadequately, if at all. Below is an illustration of the range of applications currently available or in development, a list that will expand (along with successes in each) over the next 20 years.

    Cell therapy will have deeply penetrated virtually every medical specialty by 2035. Most advanced will be those that target less complex tissues: bone, muscle, skin, and select internal organ tissues (e.g., bioengineered bladder, others). However, development will have also followed the money. Currently, development and use of conventional technologies in areas like cardiology, vascular, and neurology entails high expenditure that creates enormous investment incentive that will drive steady development of cell therapy and tissue engineering over the next 20 years, with the goal of better, long-term and/or less costly solutions.
  • Gene therapy will be an option for a majority of genetically-based diseases (especially inherited diseases) and will offer clinical options for non-inherited conditions. Advances in the analysis of inheritance and expression of genes will also enable advanced interventions to either ameliorate or actually preempt the onset of genetic disease.

    As the human genome is the engineering plans for the human body, it is a potential mother lode for the future of medicine, but it remains a complex set of plans to elucidate and exploit for the development of therapies. While genetically-based diseases may readily be addressed by gene therapies in 2035, the host of other diseases that do not have obvious genetic components will resist giving up easy gene therapy solutions. Then again, within 20 years a number of reasonable advances in understanding and intervention could open the gate to widespread “gene therapy” (in some sense) for a breadth of diseases and conditions –> Case in point, the recent emergence of the gene-editing technology, CRISPR, has set the stage for practical applications to correct genetically-based conditions.
  • Drug development will be dramatically more sophisticated, reducing the development time and cost while resulting in drugs that are far more clinically effective (and less prone to side effects). This arises from drug candidates being evaluated via distributed processing systems (or quantum computer systems) that can predict efficacy and side effect without need of expensive and exhaustive animal or human testing.The development of effective drugs will have been accelerated by both modeling systems and increases in our understanding of disease and trauma, including pharmacogenomics to predict drug response. It may not as readily follow that the costs will be reduced, something that may only happen as a result of policy decisions.
  • Most surgical procedures will achieve the ability to be virtually non-invasive. Natural orifice transluminal endoscopic surgery (NOTES) will enable highly sophisticated surgery without ever making an abdominal or other (external) incision. Technologies like “gamma knife” and similar will have the ability to destroy tumors or ablate pathological tissue via completely external, energy-based systems.

    By 2035, technologies such as these will measurably reduce inpatient stays, on a per capita basis, since a significant reason for overnight stays is the trauma requiring recovery, and eliminating trauma is a major goal and advantage of minimally invasive technologies (e.g., especially the NOTES technology platform). A wide range of other technologies (e.g., gamma knife, minimally invasive surgery/intervention, etc.) across multiple categories (device, biotech, pharma) will also have emerged and succeeded in the market by producing therapeutic benefit while minimizing or eliminating collateral damage.

Information technology will radically improve patient management. Very sophisticated electronic patient records will dramatically improve patient care via reduction of contraindications, predictive systems to proactively manage disease and disease risk, and greatly improve the decision-making of physicians tasked with diagnosing and treating patients.There are few technical hurdles to the advancement of information technology in medicine, but even in 2035, infotech is very likely to still be facing real hurdles in its use as a result of the reluctance in healthcare to give up legacy systems and the inertia against change, despite the benefits.

  • Personalized medicine. Perfect matches between a condition and its treatment are the goal of personalized medicine, since patient-to-patient variation can reduce the efficacy of off-the-shelf treatment. The thinking behind gender-specific joint replacement has led to custom-printed 3D implants. The use of personalized medicine will also be manifested by testing to reveal potential emerging diseases or conditions, whose symptoms may be ameliorated or prevented by intervention before onset.
  • Systems biology will underlie the biology of most future medical advances in the next 20 years. Systems biology is a discipline focused on an integrated understanding of cell biology, physiology, genetics, chemistry, and a wide range of other individual medical and scientific disciplines. It represents an implicit recognition of an organism as an embodiment of multiple, interdependent organ systems and its processes, such that both pathology and wellness are understood from the perspective of the sum total of both the problem and the impact of possible solutions.This orientation will be intrinsic to the development of medical technologies, and will increasingly be represented by clinical trials that throw a much wider and longer-term net around relevant data, staff expertise encompassing more medical/scientific disciplines, and unforeseen solutions that present themselves as a result of this approach.Other technologies being developed aggressively now will have an impact over the next twenty years, including medical/surgical robots (or even biobots), neurotechnologies to diagnose, monitor, and treat a wide range of conditions (e.g., spinal cord injury, Alzheimer’s, Parkinson’s etc.).

The breadth and depth of advances in medicine over the next 20 years will be extraordinary, since many doors have been recently opened as a result of advances in genetics, cell biology, materials science, systems biology and others — with the collective advances further stimulating both learning and new product development. 


See the 2016 report #290, “Worldwide Markets for Medical and Surgical Sealants, Glues, and Hemostats, 2015-2022.”

Where is the medtech growth?

Medical technology is, for many of its markets, being forced to look for growth from more sources, including emerging markets. Manufacturers are able to gain better margins through innovation, but their success varies by clinical application.

Cardiology. A demanding patient base (it’s life or death). Be that as it may, there are few new or untapped markets, only the opportunity for new technologies to displace existing markets. Interventional technologies are progressively enabling treatment of larger patient populations, but much growth will still be from emerging markets.

Wound management. Even the most well-established markets will see growth from innovation. The wound market just needs less growth to be happy, since small percentage growth becomes very large by volume. And yet, some of the most significant growth in the long run will be for more advanced

Surgery. Every aspect of surgery seems to be subject to attempts to improve upon it. Robotics, endoscopy, transcatheter, single-port, incisionless, natural orifice. Interventional options are increasing the treatable patient population, and it seems likely that continued development (e.g., materials, including biodegradables, use of drug or other coatings, including cells) will yield more routine procedures for more and different types of conditions, many of which have been inadequately served, if it all.

Orthopedics. Aging populations demanding more agility and mobility will drive orthopedic procedures and device use. Innovation still represents some upside, but more from 3D printing than other new technologies being introduced to practice.

Tissue/Cell Therapy. This is a technology opportunity (and represents radical innovation for most clinical areas), but it is also a set of target clinical applications, since tissues/cells are being engineered to address tissue or cell trauma or disease. Growth is displacing existing markets with new technology, such as bioengineered skin, tendons, bladders, bone, cardiac tissue, etc. These are fundamentally radical technologies for the target applications.

Below is my conceptual opinion on the balance of growth by clinical area coming from routine innovation (tweaks, improvements), radical innovation (whole new “paradigms” like cell therapy in cardiology), and emerging market growth (e.g., China, S. America).

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Source: MedMarket Diligence, LLC.

What is the ideal wound product?

The previously accepted wisdom was that a wound healed best when it was kept as dry as possible. In 1962, George Winter, a British-born physician, published his ground-breaking wound care research. His paper, (Nature 193:293. 1962), entitled, “Formation of the scab and the rate of epithelization of superficial wounds in the skin of the young domestic pig,” demonstrated that wounds kept moist healed faster than those exposed to the air or covered with a traditional dressing and kept dry. Dr. Winter’s work began the development of modern wound dressings which are used to promote moist wound healing.

Natural skin is considered the ideal wound dressing, and therefore wound dressings have been designed to try to reproduce the advantages of natural skin. Today, experts feel that a wound dressing should have several characteristics if it is to serve its purpose. A wound dressing should:

  • Provide the optimal moisture needs for the particular wound
  • Have the capacity to provide thermal insulation, gaseous exchange, and to help drainage and debris removal, which promotes tissue reconstruction
  • Be biocompatible without causing any allergic or immune response reaction
  • Protect the wound from secondary infections
  • Be easily removable without causing any trauma to the delicate healing tissues.

There are hundreds of dressings to choose from, but they all fall into one of a few categories. The healthcare provider will select a dressing by category, according to availability and familiarity of using that particular dressing.

Occlusive dressings are those which are air- and water-tight. An occlusive dressing is frequently made with some kind of waxy coating to ensure a totally water-tight bandage. It may also consist of a thin sheet of plastic affixed to the skin with tape. An occlusive dressing retains moisture, heat, body fluids and medication in the wound. There are several types of occlusive dressings, which are discussed below.

It should be remembered that proper wound care, especially of a chronic wound, is a complex process, as much art as science; a trained healthcare provider assesses the wound as it goes through various stages, and applies the appropriate wound dressings as the need arises. Unfortunately, the most appropriate dressing is not always used, due perhaps to confusion around which type of dressing to apply, or because certain dressings—especially advanced dressings—either may not be available in the facility, or may not be reimbursed by the country’s healthcare system, or may simply be too expensive. This remains true even in some of the developed countries.

The following table summarizes potential applications for various types of wound care products, with selected examples. This summary is meant as a guideline and an illustration of the fact that different dressing types may find use in various types of wounds. In addition, as a wound heals, it may need a different type of dressing. Here again the wound care professional’s judgment and training come into play.

Dressing categoryProduct examplesDescriptionPotential applications
FilmHydrofilm, Release, Tegaderm, BioclusiveComes as adhesive, thin transparent polyurethane film, and as a dressing with a low adherent pad attached to the film.Clean, dry wounds, minimal exudate; also used to cover and secure underlying absorptive dressing, and on hard-to-bandage locations, such as heel.
FoamPermaFoam, PolyMem, BiatainPolyurethane foam dressing available in sheets or in cavity filling shapes. Some foam dressing have a semipermeable, waterproof layer as the outer layer of the dressingFacilitates a moist wound environment for healing. Used to clean granulating wounds which have minimal exudate.
HydrogelHydrosorb Gel Sheet, Purilon, Aquasorb, DuoDerm, Intrasite Gel, Granugel,Colloids which consist of polymers that expand in water. Available in gels, sheets, hydrogel-impregnated dressings.Provides moist wound environment for cell migration, reduces pain, helps to rehydrate eschar. Used on dry, sloughy or necrotic wounds.
HydrocolloidCombiDERM, Hydrocoll, Comfeel, DuoDerm CGF Extra Thin, Granuflex, TegasorbÕ Nu-DermMade of hydroactive or hydrophilic particles attached to a hydrophobic polymer. The hydrophilic particles absorb moisture from the wound, convert it to a gel at the interface with the wound. Conforms to wound surface; waterproof and bacteria proof.Gel formation at wound interface provides moist wound environment. Dry necrotic wounds, or for wounds with minimal exudate. Also used for granulating wounds.
AlginateAlgiSite, Sorbalgon Curasorb, Kaltogel, Kaltostat, SeaSorb, TegagelA natural polysaccharide derived from seaweed; available in a range of sizes, as well as in ribbons and ropes.Because highly absorbent, used for wounds with copious exudate. Can be used in rope form for packing exudative wound cavities or sinus tracts.
AntimicrobialBiatain Ag, Atrauman Ag, MediHoneyBoth silver and honey are used as antimicrobial elements in dressings.Silver: Requires wound to be moderately exudative to activate the silver, in order to be effective
NPWDSNaP, V.A.C. Ulta, PICO, Renasys (not in USA), Prospera PRO series, Invia LibertyComputerized vacuum device applies continuous or intermittent negative or sub-atmospheric pressure to the wound surface. NPWT accelerates wound healing, reduces time to wound closure. Comes in both stationary and portable versions.May be used for traumatic acute wound, open amputations, open abdomen, etc. Seems to increase burn wound perfusion. Also used in management of DFUs. Contraindicated for arterial insufficiency ulcers. Not to be used if necrotic tissue is present in over 30% of the wound.
Bioengineered Skin and Skin SubstitutesAlloDerm, AlloMax, FlexHD, DermACELL, DermaMatrix, DermaPure, Graftjacket Regenerative Tissue Matrix, PriMatrix, SurgiMend PRS, Strattice Reconstructive Tissue Matrix, Permacol, EpiFix, OASIS Wound Matrix, Apligraf, Dermagraft, Integra Dermal Regeneration Template, TransCyteBio-engineered skin and soft tissue substitutes may be derived from human tissue (autologous or allogeneic), xenographic, synthetic materials, or a composite of these materials.Burns, trauma wounds, DFUs, VLUs, pressure ulcers, postsurgical breast reconstruction, bullous diseases

Source: MedMarket Diligence, LLC; Report #S251.