Medtech financings down significantly in April

 

The number and aggregate amount of financings for medical technology have taken a significant drop compared to one month ago. In March, we recording financings in excess of $359 million.  Financings for the month of April, thus far, total only $139 million, at least a 60% drop.

Below are the specific financings we have identified:

  • Orthopedics startup MedShape raises $8M (shape-changing polymer material that helps fuse bone to bone and soft tissue to bone, for use in shoulder cuff repairs)
  • CeraPedics, Inc. Closes $15 Million Series B Financing (bone graft subdtitute and other osteovbiologics)
  • Cianna Medical Completes $10 Million Funding Round for SAVI Technology (breast cancer brachytherapy)
  • ORTHOCON Announces Appointment of New CEO and $25 Million Series B Financing (implantable devices for drug delivery to bone)
  • ProTip SAS (Strasbourge, France) receives $1.3 million in Series A funding for development of its artificial larynx
  • iZumi raises $20 million, from Kleiner Perkins Caufield & Byers (stem cell development)
  • ViewRay gets second tranche of $25 million investment, cinches Siemens partnership (device to use MRI to direct gamma rays to target cancer tumors)
  • iScience Interventional Corp. raises $20.5 million in Series F financing (surgical device for treatment of glaucoma)
  • Sonoma Orthopedic secures $12 million in its third round of funding (device to repair wrist, clavicle fractures)
  • Azellon Ltd has raised $2.3 million for development of its "cell bandage" technology used to repair damaged knee meniscus

 

Worldwide coronary stents market

The global market for drug-eluting, bare and bioresorbable stents for the treatment of coronary artery disease is in a "growth and proliferation" phase, as the market for these devices is growing steadily through application to growing patient caseload, and as the number of companies with approved products or products in development multiplies.

The bulk of interest in this market continues to reside in drug-eluting stents for their ability to prevent the high rates of restenosis seen with initially marketed stent designs.  And with the "late stage thrombosis" concern of these stents an apparently temporary blip in the technologies’ prospects, the market is on a very strong growth track.

Over 75 companies are active in this field, encompassing not only drug-eluting stents but also bare metal stents and bioresorbable stents.  While bare metal stents have been eclipsed by drug-eluting stents, the use of different metals, shapes and other innovations are being pursued to minimize the tendency of bare stents to induce an inflammatory or other response leading to restenosis.  Similarly, bioresobable stents represent another alternative to drug-coating in minimizing restenosis, or offer other benefits, by degrading over time to leave, ideally, a recanalized lumen that free of not only restenosis but stent as well.

c245-cvrThe worldwide coronary stent market is the subject of the May 2009 report by MedMarket Diligence, described below:

This report details the worldwide market for the use of coronary stents in the treatment of coronary artery disease. The report assesses the treatment of coronary artery disease by alternative treatment methodologies (percutaneous intervention with or without stenting, coronary artery bypass grafting alternatives and other medical/surgical treatment options), with estimated current/forecast caseload across treatment types. The report details currently approved coronary stents, providing data on current and forecast impact on the market. The report also details the current state of product development in bare stents, drug-coated or drug-eluting stents and bioabsorbable stents in coronary applications and details the products under development, the anticipated timeline and impact of their market introduction. The report assesses the current and ten-year forecast global market for coronary stents, with segmentation by U.S., Europe, Asia/Pacific and Rest of World. The report provides competitor market shares by these geographic regions. The leading and key emerging coronary stent manufacturers are profiled with current product offerings, development status and market strengths/advantages.

The report is described in detail, with table of contents and list of exhibits here.

 

Bone morphogenic proteins in spine surgery

Bone Morphogenetic Proteins (BMPs) are a group of growth factors and cytokines known for their ability to induce the formation of bone and cartilage. Dr. Marshal Urist initially discovered the activity of bone morphogenetic proteins in 1965. Since then, a number of types of BMP have been discovered; some have found therapeutic uses in areas such as spinal fusion. The use of BMPs adds from $6,000 to $10,000 to the cost of surgery, but this may be slight relative to the cost of repeated surgical interventions that may be needed if BMPs are not used.

 

Bone growth stimulatory proteins, peptides and devices
 
Vendor

Product

Acologix

Bone Growth Protein (AC-IOO)

BioSET

B2A Peptide combined with HA/TCP (Amplex)

Bonebiologics

Bone Growth Protein (UCB-I)

DePuy Spine

Growth Differentiation Factor 5 (GDF-5)

Medtronic Sofamor Danek

Bone Morphogenetic Protein-2 (InFuse)

Scil

STO 1 Spine Fusion Device

Stryker Spine

Osteogenic Protein- 1 (OP-I)
 
Source: MedMarket Diligence report #M510, Worldwide Spine Surgery 2008-1017.

 

BMPs are the only known proteins capable of inducing new bone formation. In some tests, they have demonstrated bone growth stimulation superior to that of autogenous bone graft. Two recombinant rhBMPs and associated carrier/delivery systems have received approval from the FDA: OP-1 (Stryker) and the InFUSE™ system (Medtronic). OP-1 consists of rh-BMP-7 and bovine collagen, which is reconstituted with saline to form a paste. The addition of carboxymethylcellulose forms a putty. The InFUSE™ system consists of rh-BMP-2 on an absorbable collagen sponge carrier. To date, rhBMP-2 has been approved by the FDA for the treatment of L5-S1 degenerative disease and used along with titanium spacers (cages) placed anteriorly. The anterior approach was chosen because it is the easiest way to shelter the BMP within the spine. By using a collagen sponge soaked with BMP and then placing it within the cage, there is decreased possibility that the material could seep into other places and form bone where it is not needed or wanted. Use of BMPs in spine fusion has significantly changed spinal fusion, in that there is less blood loss, less pain, shorter surgery times, shorter recovery times and frequently better fusion than when autologous grafts are harvested from the iliac crest.

OP-1 received on-label indications for use as an alternative to autograft in recalcitrant long bone non-unions where use of autograft is unfeasible and alternative treatments have failed; and for use as an alternative to autograft in compromised patients requiring revision posterolateral lumbar spinal fusion, for whom autologous bone and bone marrow harvest are not feasible or are not expected to promote fusion. Depending upon the insurance system, examples of compromising factors may include osteoporosis, smoking and diabetes.

A recent study by JR Dimar and colleagues (Spine. 2006; 31(22):2534-2539) involved 98 subjects randomized to receive either autologous bone graft or rhBMP-2 for single-level posterolateral fusions of the lumbar spine for degenerative disease. The authors report a higher fusion rate at 24 months (88% vs. 73%), faster surgical times and less blood loss for the rhBMP group. No other measures were significantly different, including Sf-36 scores, Oswestry Index measures, or pain index scores.
The InFUSE Bone Graft has received FDA approval when used in conjunction with 1 of 2 interbody fusion devices, in other words, with either the LT-Cage Lumbar Tapered Fusion Device or the Inter Fix RP Threaded Fusion Device, in spinal fusion procedures in skeletally mature patients with degenerative disc disease at 1 level from L2-S1, and for the treatment of acute, open fractures of the tibial shaft.

Both OP-1 and the InFUSE Bone Graft/LT-Cage Lumbar Tapered Fusion devices are contraindicated in patients who are pregnant, who may be allergic to any of the materials contained in the devices, who have an infection near the area of the surgical incision, who have had a tumor removed from the area of the implantation site or currently have a tumor in that area, or who are skeletally immature. These contraindications reflect continued concern that BMPs may cause unwanted bone growth in adolescents, whose skeletal systems are still growing, or in or near tumors or where tumors used to be.
 

High strength medical glues and adhesives

Originally from MedMarket Diligence Report #S175. See the 2012 Report #S190, “Worldwide Surgical Sealants, Glues and Wound Closure, 2010-2017.” See also “High-Strength Adhesives versus Sutures/Staples in Wound Closure” from the 2012 Report #S190.

Cyanoacrylate products are the main form of high-strength surgical glue that is approved for human clinical use in the worldwide market. A number of new materials are under development for internal use in particular, but these represent new chemical entities and their commercialization is likely to be delayed by regulatory requirements.

Sutures will be replaced by cyanoacrylate glues in many procedures over the next 10 years but these adhesives do not represent the ideal alternative to suturing. Cyanoacrylate glues used for external skin closure are approximately five times less strong than sutures, and cyanoacrylates produce cytotoxic compounds as part of the curing process when used for securing torn or excised tissue. This has delayed the development and clinical evaluation of these potentially useful materials for internal surgical procedures. However, cyanoacrylate glues are marketed actively by a number of companies for topical wound closure in accident/emergency situations and in surgical closure.

 Companies Commercializing Cyanoacrylate-based High-Strength Medical Adhesives

cyanoacrylates

Source: MedMarket Diligence. See 2012 updated report #S190.

Active programs are under development in three categories of new high-strength adhesive closure and securement products. The first of these comprises the application of medical grade cyanoacrylates to internal procedures for many new surgical indications and the development of procedure-enabling devices for the delicate and precise application of these strong adhesives will lead to strong market segment growth. The second category of new products will arise from improvements and new indications for existing biomaterial adhesives. The third category of new products will arise over the next decade and will include new polymer adhesives based on new chemistries.

Growth in high strength medical adhesives is in excess of 20% annually due to recent regulatory approvals and will be sustained, though at more modest rates, over the next decade. It will be fueled by increased incidence of surgery, greater adoption of these cyanoacrylate and newer adhesive products for internal surgical applications, and the need for improved, fast-acting and easy-to-use products for use in minimally invasive procedures. In addition, it is becoming recognized that these products have a role to play in reducing infection and improving cosmesis of surgical wounds to the surface of the skin and this will also drive the value of this attractive market segment.


See the 2012 Report #S190, “Worldwide Surgical Sealants, Glues, Wound Closure and Anti-Adhesion Markets, 2010-2017.”

Opportunities in medical technology markets for surgical closure and securement

suturesFor over a hundred years, simple wound closure was achieved through the use of well-established suturing techniques and products. Early in the 1980s the need to control bleeding during new surgical procedures led to an increased use of biological hemostats and sealants. Made from human fibrin as well as thrombin, collagen and gelatine from other species, these materials came into widespread use, particularly in Europe and Asia, led by homologous, pooled, fibrin products such as Beriplast from CSL Behring and Tisseel from Baxter. It was not until 1997 that homologous, pooled fibrin products were approved for use in the United States. The products offer significant benefits for surgical procedures where blood loss is a major factor, but are not strong enough to be used alone for wound closure; consequently they are usually used as adjuncts to suturing.

During the 1990s an opportunity for new surgical closure products was created by the introduction of many new minimally invasive procedures. The ensuing product demand was temporarily addressed with sutures and suturing/stapling devices, autologous fibrin prepared prior to the surgical procedure, bovine and porcine hemostasis products (based on thrombin, collagen and gelatin) and chemically derived cellulose products. However, these products were less than ideal for wound closure and, as a result, were largely (and are still) used for adjunctive hemostasis. The unfilled need for more advanced products, and the huge market potential, led to the creation of biotech-based companies targeting surgical closure products. In the early 1990s this market expanded with the advent of products for adhesion prevention (prevention of fibrotic repair after surgical interventions).

The market for surgical closure and securement has entered a phase in which major driving forces are the introduction of new procedures and techniques by the surgical profession, the development by the medical device industry of new wound closure devices and biomaterials, and the growing willingness of surgical specialists to use these devices in appropriate circumstances. There is now a continuum between simple closure using sutures and the use of specially designed devices and delivery systems with new bioresorbable securement materials either as supplements to conventional closure methodology or as stand-alone replacements.

sealant-mini-forecast1MedMarket Diligence has completed a global analysis of the market for surgical closure and securement.  The report details the complete range of sealants & glues technologies used in traumatic, surgical and other wound closure, from tapes, sutures and staples to hemostats, fibrin sealants/glues and medical adhesives. The report details current clinical and technology developments in this huge and rapidly growing worldwide market, with data on products in development and on the market; market size and forecast; competitor market shares; competitor profiles; and market opportunity. The report is described in full, with a detailed table of contents and list of exhibits, here.
 

New surgical techniques drive market opportunity in surgical sealants, glues market

From MedMarket Diligence Report #S175, "Worldwide Surgical Sealants, Glues, Wound Closure and Anti-Adhesion Markets, 2009-2013."


In cardiovascular and spine surgery, multi-billion dollar markets were created from entirely new procedures between 1980 and 2000, with subsequent segmentation in later years particularly as new minimally invasive procedures were developed towards the end of the 20th century. For example, in the cardiovascular arena the development of new procedures for angioplasty and bypasses in the late 1980s led to these procedures being performed in increasing numbers. This increase was driven by lowered risk associated with the new procedures, new product availability, and surgeon capability coupled with substantial changes in demographics caused by aging, lifestyle and economics. For example, it is estimated that approximately 20% of the over 80-year-old population suffers from some form of coronary heart disease in the United States, and the development of angioplasty procedures created a new preferable (to open heart surgery) treatment for this population.

Whereas in the United States there were 50,000 open heart surgery treatments in 1980, towards the end of the twentieth century there were 150,000 open heart bypass operations per year. There are approximately 375,000 cardiac vascular reconstruction procedures per year. In cost terms, each angioplasty in the United States costs approximately $8,000 and bypass operations cost approximately $25,000. Surgical closure and securement products are routinely used in these procedures, and new techniques like this cardiovascular example, with associated new technologies, are likely to arise in the next decade to create new market opportunities.

Another example of a new buoyant market segment is that of spine fusion. Until the 1980s spinal surgery focused on multi-level segmental fusion procedures to fuse together several vertebrae to decrease the chance of failure at the bone metal interface. Fixation methods using Harrington hook and rod systems, Luque rods, and wires were used to achieve fusion. These procedures are notable by their invasive nature; they are associated with significant trauma and require substantial rehabilitation care for successful outcome. They were therefore initially used only in extreme cases of congenital deformity and cases of extreme trauma and pain.

In the mid- to late 1980s, a number of manufacturers developed bone screws for use in combination with these hooks and rods, which improved the achievement of stability without requiring multi-level fusion, and the emergence of threaded fusion cages in the mid-1990s added to the surgeon’s treatment options, with resultant increase in fusion success rates. The market for these products grew from tens of millions in 1980 to a $2.4 billion world-wide market in 2000. We forecast that such new techniques will create new market opportunities in the medical devices market for improved adjunctive products for surgical closure and securement.


From MedMarket Diligence Report #S175, "Worldwide Surgical Sealants, Glues, Wound Closure and Anti-Adhesion Markets, 2009-2013."

 

Coronary stent designs, materials

Below is an excerpt from the April 2009 Report #C245, "Worldwide Market for Drug-Eluting, Bare and Other Coronary Stents, 2008-2017."

cypher-stentThe materials used in coronary stents must be flexible, supportive, capable of expansion, and biocompatible. Typically, foreign materials implanted into the human body results in trauma, inflammation, immune response and eventual healing and/or scarring. Materials that are not biocompatible can induce many complications, including cytotoxic chemical buildup and chronic inflammation.

Most stents are built on a stainless steel platform, the least-expensive stent material available. Unfortunately, stainless steel is not fully compatible with the human body and implantation usually is followed closely by restenosis and thrombosis. In addition, stainless steel can pose difficulties related to some types of imaging, such as magnetic resonance. As such, researchers are working to develop alternative platform materials such as gold, titanium, cobalt-chromium alloy, tantalum alloy, nitinol and several types of polymer.

Materials that are not biocompatible can cause one of any number of complications. The ideal coronary stent surface does not cause a reaction in the human body.

For quite some time, it has been known that gold is biocompatible and usually inert, as well as highly visible. Cobalt-chromium was first developed for use in watch springs. Newer variations have proven to be effective stent materials. Tantalum is a shiny, flexible, and highly radio-opaque metal. While it is more brittle than stainless steel, tantalum has proven to be quite resistant to corrosion.
Nitinol (55% nickel and 45% titanium and named from the “Nickel Titanium Naval Ordinance Laboratory, sometimes called NiTi) is highly biocompatible, decreases the rate of corrosion, is very flexible and has excellent shape memory when heated to a certain temperature. Unfortunately, nitinol can be difficult to manufacture; as little as a 0.01% change in composition can drastically alter the temperature at which the alloy is transformed. In addition, the allow must be created in a vacuum as the titanium component is highly reactive to air-borne oxygen and nitrogen particles.

Certain polymers have found use as stent materials. Silicone (a condensation polymer) induces low rates of tissue trauma, but it also presents challenges in terms of biodurability, tensile and coil strength, and inner-to-outer diameter. Polyethylene and polyurethane have been used as stent materials, however, they have been found to induce sludge in 20%–30% of patients. These materials also encourage protein adherence and biofilm formation. While polyurethane is one of the most reactive of stent materials used, it does have good tensile and coil strength.

Some polymers are biodegradable, bioabsorbable, or bioerodible. Biodegradable or bioabsorbable stents contain a major component (such as an enzyme or microbe) that degrades quickly enough to make them appropriate for short-term uses. A bioerodible polymer is a water-insoluble polymer that has been converted into a water-soluble material. Biodegradable materials can form an effective stent coating because they can be mixed with an antirestinotic drug and will degrade within a few weeks, thus releasing the drug into the surrounding tissue and reducing the risk of restenosis. Examples of biodegradable polymers are: polyesters, polyorthoesters and polyanhydrides. Collagen is also very biocompatible and reduces the rate of restenosis and thrombosis. In addition, anticoagulants and fibrinolytic agents bound to the collagen can aid in drug delivery.

However, studies have shown that the stent surface after biodegradation can be very uneven and, as such, can induce various cells to adhere to the surface. This in turn produces an increased risk of complications.

Shape-memory polymers can be used to produce a device that will transition from a temporary state to a different (permanent) state through the inducement of a stimulus of heat or cold.

 

Drug-Eluting Stents’ New Growth and Opportunities: Any Doubts?

  *   *   *
See the December 2015 report, “Global Market Opportunities in Peripheral Arterial and Venous Stents, Forecast 2020”. A $500 advance discount is available until publication.
details
  *   *   *

The worldwide market for drug-eluting, as well as bare, bioresorbable and other stents, is now the subject of the May 2009 report by MedMarket Diligence, Report #C245.

Below is an excerpt from MedMarket Diligence’s coverage of  the drug-eluting stents market in mid-2008.  The previous scarcity of long term data left some uncertainty about DES’ clinical and market potential, compared to bare stents or even coronary artery bypass grafting, but the completion of multiple clinical trials has gone a long way toward ensuring at least several years of solid growth and the proliferation of competitors in the DES market.


After clinical trial results were released in 2006 showing that bare metal stents had outperformed drug-eluting stents (DESs), the market for DESs took what turned out to be fairly minor hit, with some physicians backing away from the newer technology and choosing to implant bare metal stents instead. Subsequent to those results, a number of studies revealed that DES offer better outcomes with morbidity that is competitive with bare metal stents (see the clinical trials list here).

Four-year data presented in September 2007 at the European Society of Cardiology meeting showed that in a 35,000-patient Swedish registry, patients receiving DESs are not at a higher risk of dying or suffering a heart attack as compared to patients receiving bare metal stents. While DESs do present a small increased risk of late-stent thrombosis after the first year, this is offset by better outcomes in the early months after implantation.

Nonetheless, it remains that stent sales have decreased across the board over the last two years and many physicians still need to be convinced of the devices’ performance and safety. In addition, opportunity is still great for those who would develop new DES technology that can further decrease the rate of restenosis.

The fourth quarter of 2007 proved to be the worst yet for the DES market. While some studies showed that DESs comprised nearly 90% of all stents implanted in 2006, that figure fell to roughly 60% by the end of 2007. These declines—fueled by restenosis concerns as well as studies showing that in some patients, stenting should be delayed in favor of drug therapy—led to layoffs at Boston Scientific and Johnson & Johnson. Now that the market has leveled off, the percentage of DES stents implanted seems to be holding at roughly 60%.

Meanwhile, the FDA proposed in March 2008 more stringent guidelines for DES clinical trials. Under the new guidelines companies must submit clinical trial data on patients at one and two years post-op, as compared to the previously required nine-month period. In addition, companies should continue to monitor patients for five years post-op. While this does not affect stents currently in the market (namely Cypher by Johnson & JohnsonCordis, Taxus Liberte by Boston Scientific, and Endeavor by Medtronic), it does result in a significant delay for companies bringing their first DES to market.

Johnson & Johnson

Johnson & Johnson was the first company to bring a DES to market through its Cordis subsidiary. However, Cordis saw a 15% operational sales decline in the first quarter of 2008 as compared to the prior year, primarily due to increased competition as well as contraction of the DES market worldwide.

In December 2007, Johnson & Johnson unveiled a new ad campaign designed to reassure consumers as to the safety of its Cypher stent as well as combat the competition in the market for DES. The company also set up a web site (http://www.cypherusa.com) to provide marketing and general product information to patients and physicians. The direct-to-consumer marketing approach has been criticized by many as an effort by the company to minimize physician input as to which procedures would be appropriate for which patients.

In May 2007, Johnson & Johnson announced it would discontinue marketing its CoStar stent outside the United States, would no longer seek U.S. FDA approval of the device, and had ceased ongoing clinical trials for the stent. The CoStar stent was developed by Conor Medsystems, a company Johnson & Johnson had purchased a few months earlier. The decision was made after the CoStar failed to meet its primary goal in the COSTAR II study. In the COSTAR II study, the stent was compared to Boston Scientific’s Taxus Express2 (also a paclitaxel-coated stent). While the CoStar did not present safety issues, neither did it prove superiority to the Taxus stent. Researchers said the CoStar stent presented ineffective dosing of paclitaxel, resulting in more frequent repeat revascularization procedures. The company is now working to develop a new version of the CoStar that uses sirolimus, the drug used on the Cypher stent. In a market where physicians have been reverting back to implanting bare metal stents due to performance issues of DESs, product manufacturers are looking for devices that will not only match the performance of but will outperform currently available DESs.

In other disappointing news, Conor’s GENESIS study involving a pimecrolimus-eluting Corio stent was terminated in late March 2008. The study involved three devices: the company’s Corio stent; its dual-drug (pimecrolimus and paclitaxel) SymBio stent; and its paclitaxel CoStar stent. After six months follow-up, in-stent late loss was greatest with the Corio stent, mid-range with the SymBio stent and least with the CoStar stent.

A new randomized clinical trial dubbed the RES-ELUTION study began in March 2008 to compare a Conor coronary stent that elutes sirolimus to Boston Scientific’s Taxus Liberte paclitaxel-eluting coronary stent. The primary endpoint of the study is angiographic in-stent late lumen loss at six months. Secondary endpoints include target lesion failure, target vessel failure, major adverse cardiac events (MACE), stent thrombosis, target lesion revascularization, target vessel revascularization, and angiographic in-stent and in-segment binary restenosis at six months. The multicenter study will be conducted at 40 sites outside the United States and resulting data will be used to support a CE Mark filing.

Boston Scientific

Among the sets of clinical data released over the past several months, Boston Scientific announced positive data from the ARRIVE registries and the TAXUS studies. In addition, Boston Scientific announced in February 2008 the start of the PROENCY registry, which will assess different Olimus-eluting stents, including its Promus/Xience V (everolimus), Medtronic’s Endeavor (zotarolimus) and Johnson & Johnson’s Cypher (sirolimus) stents. The registry will enroll up to 2,500 patients with simple and complex lesions at multiple sites in several European countries. Half of the patients will receive the Promus stent and half will receive either the Cypher or the Endeavor stent to attain a 2:1:1 ratio. The primary endpoint will be the rates of MACE (cardiac death, all myocardial infarction and target vessel revascularization) at 12 months.

Also in February 2008, a U.S. District Court in Texas reached a verdict finding that Boston Scientific’s Taxus Express and Taxus Liberte DESs infringe on a patent held by Dr. Bruce Saffran. While the jury awarded damages of $431 million, Boston Scientific plans to contest the verdict.

In May 2008, a World Intellectual Property Organization arbitration panel decided in favor of Boston Scientific, refuting a claim by Medinol alleging the Liberte and Taxus Liberte stents infringed various U.S. and European patents held by Medinol. Under the terms of the settlement agreement, Medinol holds the right to appeal to another WIPO panel.

Medtronic

In February 2008, Medtronic received FDA approval for its Endeavor zotarolimus-eluting coronary stent, becoming the third company to receive marketing approval for a DES in the United States.

In May 2008, Medtronic saw the first implants of its next-generation Endeavor Resolute stent as part of the RESOLUTE III trial comparing Medtronic’s stent to Abbott’s Xience V. The pivotal RESOLUTE III trial will be conducted in more than 100 countries outside the United States. The Endeavor Resolute stent received CE Mark approval in October 2007 and is still limited to investigational use in the United States.

The Endeavor Resolute incorporates the company’s biocompatible polymer dubbed BioLinx, designed to offer the same biocompatibility as the Endeavor’s phosphorylcholine (PC) while lengthening the amount of time the drug is exposed in the vessel. BioLinx blends hydrophilic and hydrophobic elements and is the first polymer created specifically for a DES.

Abbott Vascular

Results from clinical studies performed with Abbott Vascular’s Xience stent have been encouraging and the company expects to receive FDA approval for the device in 2008. Xience received CE Mark approval in 2006.

Over the last few months, data from the SPIRIT II and III trials have been released by the company. In May 2008, the first long-term data from the pivotal SPIRIT III trial was presented at the EuroPCR 2008 meeting showing the Xience V everolimus-eluting coronary stent performed well against Boston Scientific’s Taxus stent. At two years follow-up, the Abbott stent showed a 45% reduction in the risk of MACE (7.3% for Xience V versus 12.8% for Taxus) and a 32% reduction in the risk of target vessel failure (10.7% for Xience V versus 15.4% for Taxus). The prospective, randomized SPIRIT III trial involves 1,002 patients at several sites in the United States.

Abbott Vascular is also working on a drug-eluting, fully bioabsorbable vascular stent (BVS). The device is currently the focus of the ABSORB clinical trial, for which positive one-year results were published in The Lancet (371[9616]: 899–907, March 15, 2008), The results showed 100% procedural success in 30 patients and 94% device success (29 of 31 implantation attempts). At one year, the MACE rate was 3.3% and no late stent thromboses were recorded. The prospective, nonrandomized ABSORB trial is designed to accommodate up to 60 patients in Belgium, Denmark, France, New Zealand, Poland and The Netherlands.

Biosensors International

In April 2008, Biosensors International launched its BioMatrix drug-eluting stent outside the United States. The device combines a biodegradable polymer with the company’s proprietary drug Biolimus A9. The BioMatrix stent received CE Mark approval in January 2008.

Simultaneously with the product launch, Biosensors began enrollment in a five-year patient registry designed to track the safety and efficacy of the BioMatrix stent in up to 5,000 patients.

In March 2008, Biosensors opened enrollment in the BEACON II registry, which is designed to enroll 1,000 patients in 15 centers across Asia, Australia and New Zealand. Results from the original BEACON study were presented in October at the TCT 2007 meeting. In that study, the BioMatrix showed a 2.1% target vessel revascularization rate and an 86.5% MACE rate.

Biosensors International is also striving to make its presence known in the DES market through corporate liaisons. For instance, in Europe, Terumo markets the company’s BioMatrix under the Nobori label.

In another agreement, Biosensors acquired the remaining 50% equity of JW Medical Systems in May 2008. JW Medical Systems was established in 2003 as a 50:50 equity joint venture between Biosensors and Shandong Weigao Group in China. JW Medical Systems, which will now likely be absorbed into Biosensors, has been developing the Excel sirolimus-eluting stent. The CREATE registry study is ongoing in China and incorporates the Excel biodegradable polymer DES. Results presented in October at the TCT 2007 meeting showed the stent had achieved both primary and secondary endpoints with a MACE rate of 0.63% and 1.4%, respectively, in 30-day and 6-month follow-ups. Excel has been available commercially in China since December 2005.

Xtent

Xtent is developing its Custom NX DES, which incorporates Biolimus A9 licensed from Biosensors International. In December 2007, Xtent submitted its application for CE Mark registration, based on the CUSTOM I, II, and III trials. In March 2008, the company was informed that it would receive a response to its CE Mark application in the second quarter of 2008. Xtent had previously filed an IDE application with the FDA in September 2007 to gain the right to begin U.S. trials.

Stentys

French company Stentys is developing a bifurcated coronary DES, which was first implanted into a human patient in September 2007. The successful procedure involved a 56-year-old male patient in Siegburg, Germany. The Stentys device is unique in that the stent-opening for the side branch can be created anywhere in the stent after implantation, thus ensuring that the procedure’s success is not dependent on accurate positioning.

In March 2008, Stentys announced that it had completed an $18 million Series B round of venture financing, led by the U.K.-based Scottish Equity Partners. The financing will be used to complete clinical trials and obtain CE Mark status.

MIV Therapeutics

MIV Therapeutics (MIVT) saw the first human implantation of its hydroxyapatite-coated VESTAsync DES and the launch of the MIVT Pilot Trial in May 2007. The trial will evaluate the safety and efficacy of MIVT’s polymer-free nanoscale microporous hydroxyapatite DES for the treatment of single de novo lesions in native coronary arteries. Dr. Alexandre Abizaid performed the procedure at the Institute Dante Pazzanese of Cardiology in Sao Paulo, Brazil. The MIVT stent is based on the company’s GenX coronary stent system and incorporates a coating that is only 700 nanometers thin.

In October 2007, Dr. Abizaid performed a live four-month follow-up case at the TCT 2007 conference. The physician also implanted a VESTAsync stent into another patient as part of the same live presentation. Follow-up data on the first 13 patients in the trial showed average late-lumen loss of 0.27 mm in-stent and 0.18 mm in-lesion with 0% restenosis. IVUS analysis showed volumetric obstruction of 2.8% and all patients were thrombosis-free.

Data presented in November 2007 at American Heart Association meeting showed that in animal studies, MIVT’s VESTAsync hydroxyapatite coronary stent coating with low-dose sirolimus resulted in less fibrinoid than seen with Johnson & Johnson’s Cypher stent. The data also showed a statistically significant difference between an increase in sirolimus and an increase in fibrinoid material, a strong indicator of delayed healing. Even though the MIVT stent presented a four-fold lower dosage of sirolimus as compared to the Cypher stent, less fibrinoid was seen overall.

Nine-month VESTAsync data presented at the American College of Cardiology meeting in March 2008 was consistent with the data presented at the October 2007 TCT meeting, with no significant difference between the four- and nine-month results. In addition, no late-acquired incomplete stent apposition, stent thrombosis or MACE were reported. The company is now gearing up for a larger clinical trial accommodating approximately 100 patients.

Other DES Developments

In May 2007, Brookwood Pharmaceuticals and Targeted Technology Ventures collaborated to create a joint venture—Aeon Bioscience—to develop a new DES that would be more resistant to restenosis. Aeon Bioscience is working to develop a new polymer coating with better biocompatibility than seen with the current market leaders. In October 2007, Brookwood Pharmaceuticals was acquired by SurModics, a development that is not expected to hinder Aeon Bioscience in its product development efforts.

In October 2007, ARIAD Pharmaceuticals signed a licensing agreement with ICON Medical to develop and commercialize DES devices that incorporate ARIAD’s mTOR inhibitor, deforolimus. Under the agreement, ARIAD receives an equity stake in ICON, up to $27 million in payments based on achievement of certain clinical, regulatory and commercial milestones for two products and royalties on worldwide sales of all ICON medical devices delivering deforolimus. ICON will build the DES around its proprietary metal alloy, Nuloy.

In December 2007, Devax completed patient enrollment in its DIVERGE clinical trial evaluating its Axxess bifurcated DES. To date, 302 patients are enrolled in the prospective, multicenter trial. The Devax Axxess Biolimus A9–eluting DES is a self-expanding nitinol stent designed for treating coronary and vascular bifurcation lesions.

In June 2007, Biotronik completed enrollment in its ProLimus I study, a prospective, nonrandomized trial incorporating 61 patients at five centers in Belgium and Germany and using the company’s pimecrolimus-eluting ProGenic stent.

CardioMind began its first-in-man trial in March 2008 with its Sparrow DES, a device that is 70% smaller in diameter than other DES on the market. The CARE II clinical trial began at St. Vincent’s Hospital in Melbourne, Australia, and will eventually enroll 220 patients. The Sparrow stent incorporates the SynBiosys biodegradable polymer stent from SurModics, which will allow the stent to gradually return to a bare metal state.

Endovasc and TissueGen mutually agreed in May 2007 to dissolve their joint venture exploring development of biodegradable stents for cardiovascular, ureteral and prostate applications. All intellectual property has returned to the respective owners.

Medlogics is developing its Synergy Biomatrix non-polymeric coating, which can be applied to stainless steel, nickel titanium and cobalt chromium alloys. The Synergy Biomatrix surface is less than 2 microns thick, as compared to polymeric coatings that are typically between 7.5 and 10 microns. The coating is also biodegradable and returns the stent to bare metal after releasing the drug. Current development programs are focusing on the Cobra-P (paclitaxel) and Cobra-Q (undisclosed drug) DESs. Medlogics has received a CE Mark for its bare Cobra stent and is launching the device in Europe in 2008. In February 2008, Medlogics signed an agreement granting the company licensing rights to CV Therapeutics’ biopolymer stent coating.

Below is a sampling of active drug-eluting stent companies:

Links:
Abbott Vascular (Redwood, City, CA; http://www.abbottvascular.com)
Aeon Bioscience (Birmingham, AL; http://aeonbio.com [under construction])
Avantec Vascular (Sunnyvale, CA; http://www.avantecvascular.com [under construction])
B. Braun Melsungen (Melsungen, Germany; http://www.bbraun.com)
Lepu Medical (Beijing, China; http://www.lepumedical.com)
Bioabsorbable Therapeutics, Inc. (BTI; Menlo Park, CA; http://www.bioabsorbabletx.com)
Biosensors International (Newport Beach, CA; Singapore; http://www.biosensorsintl.com)
Biotronik (Lake Oswego, OR; Berlin, Germany; http://www.biotronik.com)
Blue Medical Devices (Helmond, The Netherlands; http://www.bluemedical.com)
Boston Scientific (Natick, MA; http://www.bostonscientific.com)
CardioMind (Sunnyvale, CA; http://www.cardiomind.com)
Conor Medsystems (Menlo Park, CA; http://www.conormed.com)
Cook Medical (Bloomington, IN; http://www.cookmedical.com)
Cordis (New Brunswick, NJ; http://www.cordis.com)
CorNova (Burlington, MA; http://www.cornova.com)
Devax (Irvine, CA; http://www.devax.net)
DISA Vascular (Cape Town, South Africa; http://www.disavascular.com)
Endovasc (Montgomery, TX; http://www.endovasc.com)
Estracure (Montreal, Quebec, Canada; http://www.duravestinc.com/estracure)
ICON Medical (Cleveland, OH; http://www.iconmedicalcorp.com [under construction])
Johnson & Johnson (J&J; New Brunswick, NJ; http://jnj.com)
JW Medical Systems (See Biosensors International)
Kaneka (Osaka, Japan; http://www.kaneka.co.jp)
Medinol (Jerusalem, Isreal; http://www.medinol.com)
Medlogics Device Corporation (MDC; Santa Rosa, CA: http://www.medlogicsdc.com [under construction])
Medtronic Vascular (Minneapolis, MN; http://www.medtronic.com)
MicroPort Medical (Shanghai, China; http://www.microport.com)
MIV Therapeutics (MIVT; Vancouver, BC, Canada; http://www.mivtherapeutics.com)
OrbusNeich (Wanchai, Hong Kong; http://www.orbusneich.com)
Relisys Medical Devices (Hyderabad, India; http://www.relisysmedical.com [under construction])
Sahajanand Medical Technologies (SMT; Surat, India; http://www.smtpl.com)
Sorin (Saluggia, Italy; http://www.sorin.com)
Stentys (Clichy, France; http://www.stentys.com)
Terumo (Shibuya-ku, Japan; http://www.terumo.co.jp)
TissueGen (Dallas, TX; http://www.tissuegen.com)
Translumina (Hechingen; Germany; http://www.translumina.de)
Vascular Concepts (Barcelona, Spain; http://www.vascularconcepts.com)
X-Cell Medical (Monmouth Junction, NJ; http://www.x-cellmedical.com)
Xtent (Menlo Park, CA; http://xtentinc.com)


The worldwide market for drug-eluting, as well as bare, bioresorbable and other stents, is now the subject of the May 2009 report by MedMarket Diligence, Report #C245.

Orthopedic biomaterials worldwide market

Definitions

Biomaterial is an abbreviated form of the term biocompatible material, which can be defined as “a synthetic or natural material used to replace part of a living system or to function in intimate contact with living tissue” . Biomaterials are intended to interface with biological systems; they may be viable or non-viable. Artificial hips, vascular stents, artificial pacemakers and catheters are all made from different biomaterials.

The category of biomaterials now generally includes biomimetic materials – synthetic constructs with compositions and properties similar to biological materials. Calcium hydroxyapatite, used as a coating on artificial hips, is a typical example; it is used as a bone replacement and facilitates attachment of an implant to living bone. The term “orthopaedic biomaterials” applies, clearly, to biomaterials used to replace, augment, heal or otherwise enhance the function of bone which is damaged or deficient as a result of disease or trauma.

The orthopaedic biomaterials field is like a cake that can be cut in various ways; for example by the types of materials used, the different structures involved, and by the clinical uses to which they are put. And of course the business of orthopaedic biomaterials can involve analysis of the market (actual and potential) and of the industry which supplies these materials and the devices of which they are made.

Worldwide Market

The total global value of the medical devices market is estimated to be more than $165 billion in 2006, with annual growth at 5.5%, led by the Americas with annual rates approaching 7%.

Orthopaedic devices are a major contributor to the global medical device market, accounting for almost $26 billion in 2006, and with a growth rate that reflects growth in the medical sector overall.

The current valuation of the orthopaedic biomaterials segment is around $7.4 billion, representing over 17% of the orthopaedic total. It is also estimated that this market segment will grow at over 13% per year, which is more than double the rate for the overall orthopaedics market. At this rate the biomaterials segment will achieve a value of $9.4 billion by 2011.

Growth in the U.S. market is expected to be somewhat faster than in Europe and significantly greater than in the developing world, partly because new biomaterials are relatively expensive and their uptake is related, in general terms, to GDP. Overall, the U.S. market for orthopaedic biomaterials is expected to grow by approximately 12% per annum over the next five years. Below is shown the segmentation of the global market by main regions and countries.

ortho-bio-ww

Source: MedMarket Diligence, Report #M625, "Emerging Trends, Technologies and Opportunities in the Markets for Orthopedic Biomaterials, Worldwide."

Any ranking of the major players in the orthopaedic biomaterials marketplace must take account of the fact that some companies have orthopaedic product offerings other than biomaterials, and/or they are subsidiaries of larger concerns which do not provide detailed breakdowns of revenues. For example, among industry leaders are Genzyme Biosurgery, DePuy and Medtronic Sofamor Danek all of which are subsidiaries, while Smith & Nephew has a range of orthopaedic product offerings not including biomaterials.

Drug-eluting, bare, bioresorbable and other coronary stent companies

Coronary stents represent a worldwide market in the $billions due to their potential to address coronary artery disease without the invasive sternotomy, while demonstrating outcomes that rival coronary artery bypass graft procedures, particularly for advanced drug-eluting coronary stents.

Given the financial stakes in the coronary stent market, it has driven the proliferation of competitors seeking to gain shares.  Below are select companies being covered in the 2009 MedMarket Diligence report #C245, "Worldwide Market for Drug-Eluting, Bare and Other Coronary Stents, 2008-2017."

Aachen Resonance GmbH, Abbott Vascular, AdvanSource Biomaterials, Aeon Bioscience, Amaranth Medical, Inc., amg International GmbH, Arterial Remodeling Technologies (ART), Atrium Medical, Avantec Vascular, B. Braun Melsungen, Balton Ltd., Beijing Lepu Medical Device, Inc., Bioabsorbable Therapeutics, Inc. (BTI), Biocompatibles International plc, Bioring SA, Biosensors International PTE Ltd., Biotronik, Blue Medical Devices B.V., Boston Scientific, Capella Inc., CardioMind, Inc., CeloNova BioSciences, CID (Carbostent & Implantable Devices) SRL, Cinvention AG (Formerly Blue Membranes), CorNova, CV Therapeutics, Devax, DISA Vascular, DSM Biomedical/Caliber Therapeutics, Elixir Medical Corporation, Estracure, eucatech AG, Eurocor GmbH, Genesis Technologies, LLC, Global Therapeutics (Cook Medical), Hexacath, ICON Interventional Systems, InspireMD, InTek Technology, Invatec S.p.A., ITGI Medical Ltd., Johnson & Johnson (Cordis, Conor Medsystems), JW Medical Systems/Biosensors International, Kaneka Corporation, Kyoto Medical Planning Co., Ltd., Lutonix, Medinol/ARIAD Pharmaceuticals, Medlogics Device Corporation (MDC), Medtronic Vascular, Miami Cardiovascular Innovations (MCVI), Micell Technologies, MicroPort Scientific Corporation, Minvasys, MIV Therapeutics (Biosync Scientific Pvt. Ltd.), mNEMOSCIENCE GmbH, NanoInterventions, LLC, Neovasc Inc., Nexeon MedSystems, Inc., Opto Circuits Ltd., OrbusNeich, Picarus NV, Possis Medical, Prescient Medical, Relisys Medical Devices, REVA Medical, Sahajanand Medical Technologies, Stentys, Terumo, Translumina, TriReme Medical, Tryton Medical, Vascular Concepts, VasoTech, Inc., X-Cell Medical, Xtent.


Purchase for download:  Report #C245, "Worldwide Coronary Stents 2009, PDF" — $2,850.00
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