Sealants, Glues, Hemostasis and Wound Closure Market, Size and Growth

The simple practice of closing wounds is not so simple, driven as it is by the fact that wounds can be the conduit for blood, infectious agents and every other liquid, gas or solid that should not enter or exit the wound.  The closure has to be readily accomplished, regardless of where the wound exists. The closure should not only prevent blood from being lost but ideally should actively stop the bleeding. The wound must stay closed despite the pressures exerted upon it. The closure should also have a minimal “footprint”, with the closure components being easily removed, absorbed or otherwise leaving the least possible trace of the closure, including scar tissue.

Hence, tapes, staples, sutures, clips, hemostatic agents, sealants, glues and other devices have been developed to get the job done.  The market for this range of closure options now reflects biologics, absorbable materials, devices and other products. Fundamentally, the market remains largely dominated by sutures and staples/clips, which have satisfied the demands of internal/external closure, easy of use, low cost, strength of closure and other considerations, not least of which is the evolving nature of surgical practice from the “open” to endo/laparoscopic. Nonetheless, tighter wound sealing, less bleeding and better outcomes in general have driven manufacturers to develop improvements.

Below is illustrated the 2014 market for the range of wound closure products along with their associated growth rates. The prospects for medical/surgical tapes are the exception to the rule, demonstrating a steady decline while better alternatives demonstrate steady growth.

Screen Shot 2015-05-20 at 10.08.13 AM

Source: MedMarket Diligence, LLC; Report #S192

Medtech Fundings in May 2015

Fundings for medical technologies in May 2015 thus far stand at $721 million, led by the (planned) $115 million IPO of EndoChoice, Inc.

Below are the top fundings for the month thus far.

Company, funding Product/technology
EndoChoice, Inc., has filed for a $115 million initial public offering according to the company Endoscopy imaging and instruments
Glaukos Corp. has filed for an $86 million initial public offering according to a regulatory filing Device-based treatment for glaucoma
Outset Medical, Inc., has raised $59.59 million of a planned $65.59 million round of funding according to a regulatory filing Dialysis technology
Shockwave Medical, Inc., has raised $40 million in a round of funding according to the company Balloon dilatation catheters integrated with lithotripsy for treatment of vascular and valvular lesions
Intact Vascular, Inc., has raised $38.9 million in a Series B round of funding according to the company Devices for minimally invasive peripheral vascular procedures
Autonomic Technologies, Inc., has raised $38 million in a Series D round of funding according to the company Microstimulator for treatment of autonomic disorders, including severe headache
AirXpanders, Inc., has filed for a $36.5 million initial public offering according to the company Breast tissue expander
AEGEA Medical, Inc., has raised $36 million in a Series C round of funding according to the company Connective water vapor treatment for menorrhagia (abnormal uterine bleeding)
Ceterix Orthopedics, Inc., has secured $35 million in debt funding according to the company Surgical instruments and other products for treatment of soft tissue injuries
Moximed, Inc., has raised $33 million of a planned $37.64 million round of funding according to a regulatory filing Extra-capsular and extra-articular knee implant for treatment of osteoarthritis

For the complete list of medtech fundings in May 2015, see link.

For a historical list of the individual fundings in medtech, by month, since 2009, see link.

Medtech fundings in April 2015

Fundings for medical technologies in April 2015 reached $615 million, led by the huge $225 million funding of Intarcia Therapeutics.

Below are the top fundings for the month.

Company, funding Product/technology
Intarcia Therapeutics has raised $225 million in a round of funding according to the company Subcutaneous, osmotic pump for drug delivery in type 2 diabetes
Mesoblast has raised $58.5 million in a round of funding by Celgene Corp. Precursor and stem cells for cell therapy
MyoKardia, Inc., has raised $46 million in a round of funding according to a regulatory filing Genetically based treatments for cardiomyopathies
Scanadu has raised $35 million in a Series B round of funding according to press reports Device that enables patients to scan and upload diagnostic information
Neuronetics, Inc., has completed a $34.3 million Series F funding round, according to the company Transcranial magnetic stimulation for the treatment of depression
Lombard Medical, Inc., has raised $26 million in financing from Oxford Finance, LLC Stent grafts for treatment of abdominal aortic aneurysm
EBR Systems, Inc., has raised $20 million in a round of funding according to the company Wireless cardiac pacing

For the complete list of medtech fundings in April 2015, see link.

For a historical list of the individual fundings in medtech, by month, since 2009, see link.

Sealants/Glues, Hemostats, Other Wound Closure Markets, Size and Growth

Products in wound closure include sutures/staples, tapes, vascular closure devices, surgical hemostats, and surgical sealants/glues.

Wound types have not changed over history, with a slight exception being the emergence (several decades ago) of femoral punctures associated with catheterization procedures. But what has changed, and what continues to evolve, is the practice of closing those wounds. Sutures, staples and tapes are a mainstay of medical practice, representing uncomplicated methods to secure wounds. And while innovators continue to change the form and function of these products to improve performance, the more recently introduced surgical hemostats, vascular closure, and surgical sealants/glues have seized significant shares of wound closure caseload and are growing marginally faster than sutures/staples and tapes. The result is and will be an erosion of traditional wound closure technology shares.

Below is illustrated the size/growth of segments in the global wound closure market.

Screen Shot 2015-04-13 at 7.05.33 AM
Source: MedMarket Diligence, LLC; “Worldwide Surgical Sealants, Glues, and Wound Closure Markets, 2013-2018″, Report #S192.

The Five Biggest Medical Technology Forces

There are five fundamental forces driving change in virtually every medical technology market. (There are many other forces, of course, that impact these markets, such as regulation, reimbursement, etc., but here I speak of forces driven by technology and the innovators employing them.) They represent challenges and opportunities — depending merely upon how companies perceive and respond to them.

Devices are no longer devices (only).

An inert medical or plastic device is likely to present little competitive threat. The device that succeeds stretches the boundaries of what a device is. Devices can be:

  • Biocompatible
  • Bioresorbable
  • Bioactive
  • Shape-shifting (e.g., nitinol)
  • Hybridized with drugs, cells, other biologics
  • Integrated with RFIDs and sensors
  • Combinations of the above

Competition comes from all directions. And so does opportunity.

Competition in medical technology has long since been defined by the device, having been replaced by the definition of the specific problem solved. And that problem is the disease state and the costs of managing and/or eliminating it. (An angioplasty catheter’s competition is not just angioplasty catheters, but also drug-eluting and/or bioresorbable coronary stents, drug-coated balloons, atherectomy, minimally invasive coronary artery bypass graft, atherosclerotic plaque-reducing drugs, etc.) Successful innovators consider all possible alternatives to solving the disease state need and define themselves by the solution, not the product. The only limitation a manufacturer has is its willingness to pursue all avenues to solving the problem.

Zero invasiveness.

Any technology that is not focused on the ideal of zero collateral damage, zero complications, and zero adverse side-effects will be threatened by those that do. The advances in materials technologies, medical/surgical techniques and understanding of pathology, among other advances, are sufficient to challenge manufacturers to pursue the goal of zero invasiveness. Just as open surgery has evolved to incisionless surgery, medical technologies increasingly take on the potential to be more like drugs, or better — treating the disease on a one-time basis with no complications whatsoever.

Decentralized, point-of-care technology.

Capital equipment is expensive, big and lethargic. A handheld imaging — ultrasound, even MRI — performed at the patient’s bedside or doctor’s office, offers enormous potential to reduce cost and increase clinical utility. But decentralization is not limited to diagnosis, since treatment is the ultimate goal and its incentives are the same. Of course, the trend moving diagnostics and therapeutics from the centralized to the point-of-care is not a new idea, but the reality is that a whole range of therapeutic devices (e.g., numerous ablation modalities) have been developed that no longer require OR suites, general anesthesia and their associated costs, and imaging systems have been shrinking to the point that words like “handheld” and “MRI” can be used in the same sentence (see Butterfly Network).

Research and development tools eliminate excuses.

R&D is inevitably challenged to evaluate ideas thoroughly, considering difficult to anticipate obstacles and rapidly evaluating ideas to reveal the best prospects and bring them to manufacturing, let alone market. But multiple technologies have been developed and put into use that can accelerate the iterative cycles of development and yield prime product candidates to bring to market — biotech, pharma, biopharm, device, drug/device and others.  Computer modeling of hemodynamic blood flow, computer simulation of drug candidates (hybridized with devices or not), 3D printing (prototypes, custom implants) and many other advances rapidly accelerate and improve the efficiency of product development of products that more perfectly fit the need and eliminate excuses for unforeseen costs and patient complications. R&D is also far more well informed — integrating more complete understanding of systems biology and the consequent downstream benefits and costs of intervening in any particular way. What is left is the ability to more rapidly evaluate and test (more) ideas and bring them to market.

 

Sticky stuff: remora, mussels, geckos, crab shells, Australian burrowing frogs, spider webs, porcupine quills, sandcastle worms

It may not be obvious what links all of these creatures, but it is their all-natural adhesiveness. While we have covered these before, today Researchers at Purdue University report on the development of new glues with industrial applications (including medical) based on glues derived from, or inspired by, mussels and oysters.

The reality is that there is a very wide range of naturally occurring “bio-glues” or other adhesives (or adhesive mechanisms) that are being evaluated for their potential use as medical/surgical glues and adhesives.

(This technique of “biomimicry”, in which products are developed that exploit or replicate features in nature, is not new. Velcro, for instance, was invented in 1941 by Swiss engineer George de Mestral, who recognized a potential product in burrs, the plant seed pods covered with hooked spines that readily attach to fur, fabrics and almost any surface that has filamentous covering.)

Below is a list of organism-derived “bio-glues”, a wide range of naturally-occurring adhesives that are being investigated for their potential development as commercial adhesives, including for medical/surgical adhesion.

Most of these have at least been preliminarily investigated as to why they have such high strength, why they adhere under certain challenging conditions and other considerations. Further research and development, in some cases to an advanced degree, has been done on a number of these to actually either directly utilize these glues, modify them or develop new ones inspired by them.

MedMarket Diligence tracks the medical/surgical markets for fibrin and other sealants, glues, hemostats, tapes, vascular closure devices, and staples/sutures/clips in Report #S192. Products specifically related to closure of wounds (excluding hemostasis*) will exceed $11 billion in sales by 2018:

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*Hemostasis is covered in report #S192.

Source: MedMarket Diligence, LLC; Report #S192.

Surgical Sealants, Glues, and Hemostats with Bioactive Agents

Excerpt from Report #S192, “Worldwide Surgical Sealants, Glues, and Wound Closure 2013-2018″.

Screen Shot 2015-03-30 at 10.14.59 AMBiologically active sealants typically contain various formulations of fibrin and/or thrombin, either of human or animal origin, which mimic or facilitate the final stages of the coagulation cascade. The most common consist of a liquid fibrin sealant product in which fibrinogen and thrombin are stored separately as a frozen liquid or lyophilized powder. Before use, both components need to be reconstituted or thawed and loaded into a two-compartment applicator device that allows mixing of the two components just prior to delivery to the wound. Because of the laborious preparation process, these products are not easy to use. However, manufacturers have been developing some new formulations designed to make the process more user friendly.

Selected Biologically Active Sealants, Glues, and Hemostats 

CompanyProduct NameDescription/
(Status*)
Asahi Kasei MedicalCryoSeal FS SystemFibrin sealant system comprising an automated device and sterile blood processing disposables that enable autologous fibrin sealant to be prepared from a patient's own blood plasma in about an hour.
BaxterArtissFibrin sealant spray
BaxterTisseelBiodegradable fibrin sealant made of human fibrinogen and human thrombin. For oozing and diffuse bleeding.
BaxterFloSealHemostatic bioresorbable sealant/glue containing human thrombin and bovine-derived, glutaraldehyde-crosslinked proprietary gelatin matrix. For moderate to severe bleeding.
BaxterGelFoam PlusHemostatic sponge comprising Pfizer's Gelfoam hemostatic sponge, made of porcine skin and gelatin, packaged with human plasma-derived thrombin powder.
Behring/NycomedTachoCombFleece-type collagen hemostat coated with fibrin glue components.
Bristol-Myers Squibb/ZymoGenetics (Sold by The Medicines Company in the US and Canada)RecothromFirst recombinant, plasma-free thrombin hemostat.
CSL BehringBeriplast P/Beriplast P Combi-SetFreeze dried fibrin sealant. Comprised of human fibrinogen-factor XIII and thrombin in aprotinin and calcium chloride solution.
CSL BehringHaemocomplettan P, RiaSTAPFreeze-dried human fibrinogen concentrate. Haemocomplettan (US) and RiaSTAP (Europe).
J&J/EthiconEvicelEvicel is a new formulation of the previously available fibrin sealant Quixil (EU)/Crosseal (US). Does not contain the antifibrinolytic agent tranexamic acid, which is potentially neurotoxic, nor does it contain synthetic or bovine aprotinin, which reduces potential for hypersensitivity reactions.
J&J/EthiconEvarrestAbsorbable fibrin sealant patch comprised of flexible matrix of oxidized, regenerated cellulose backing under a layer of polyglactin 910 non-woven fibers and coated on one side with human fibrinogen and thrombin.
J&J/EthiconBIOSEAL Fibrin SealantLow-cost porcine-derived surgical sealant manufactured in China by J&J company Bioseal Biotechnology and targeted to emerging markets.
J&J/EthiconEvithromHuman thrombin for topical use as hemostat. Made of pooled human blood.
Pfizer/King PharmaceuticalsThrombin JMIBovine-derived topical thrombin hemostat.
Stryker/OrthovitaVitagel SurgicalBovine collagen and thrombin hemostat.
Takeda/NycomedTachoSilAbsorbable surgical patch made of collagen sponge matrix combined with human fibrinogen and thrombin.
Teijin Pharma Ltd/Teijin Group (Tokyo, Japan)KTF-374Company is working with Chemo-Sero-Therapeutic Research Institute (KAKETSUKEN) to develop a sheet-type surgical fibrin sealant. Product combines KAKETSUKEN's recombinant thrombin and fibrinogen technology with Teijin's high-performance fiber technology to create the world's first recombinant fibrin sealant on a bioabsorbable, flexible, nonwoven electrospun fiber sheet.
The Medicines Company (TMC)Raplixa (formerly Fibrocaps)Sprayable dry-powder formulation of fibrinogen and thrombin to aid in hemostasis during surgery to control mild or moderate bleeding.
The Medicines Company (TMC)In development: Fibropad patchFDA accepted company's BLA application for Fibrocaps in April 2014 and set an action date (PDUFA) in 2015. In November 2013, the European Medicines Agency agreed to review the firm's EU marketing authorization application. Status update in report #S192.
Vascular SolutionsD-Stat FlowableThick, but flowable, thrombin-based mixture to prevent bleeding in the subcutaneous pectoral pockets created during pacemaker and ICD implantations.

Note: Status of products detailed in Report #S192.

Source: MedMarket Diligence, LLC