Periodic Reporting for period 1 - SpiraStent (DEVELOPMENT OF A SPIRAL LAMINAR FLOW INDUCING ENDOVASCULAR STENT FOR THE TREATMENT OF PERIPHERAL ARTERIAL DISEASE)
Periodo di rendicontazione: 2014-10-01 al 2015-02-28
Sintesi del contesto e degli obiettivi generali del progetto
Overall project objective: to develop an innovative endovascular stent to reintroduce the natural spiral laminar flow both through the stent and distal to the stent, that can be manufactured to be deployed using standard delivery system profiles. To understand and overcome the technical requirement for incorporating the nitinol SLF inducer to a nitinol stent, Phase 1 had the following objectives:
1. Validation of the modifications to existing stents as a way forward
Commercially available stents were technically evaluated to assess the capability of modification with a spiral laminar flow inducer. The results demonstrated the ability to create Spiral Laminar Flow and showed that the stent design will need to be customised to meet the performance requirements. A full testing plan (in accordance with the relevant ISO) has been produced for Phase 2.
2. Assess stent covering to see how this will affect the stent
Covered and uncovered stents were modified to determine the effect of stent covering. Mechanical tests assessed whether the covering adversely effects the structure, pliability and expected function of the stent. This allowed us to determine that modification of pre-existing stents is a technically viable option.
3. Determine the nitinol stent patent landscape and additional IP regime
Intellectual property searches were conducted to determine whether patents exist that have claimed the use of nitinol to modify blood flow through medical devices. This indicated that we have freedom to operate in this area. The company has potential to file new Patents in Phase 2 development to strengthen the current 17 Patent families in the Patent estate. The company has a further approved Trademark SLF* which describes the design platform.
4. Identify partners for manufacture and commercialization
We identified and engaged sufficient numbers of relevant, interested parties to participate in the manufacturing and route to market process. These potential partners can provide commercial services, quotations and appropriate lead-times. Parties identified were categorised into the following groups: Metal Stent Manufacture, ePTFE Covering, Assembly/Delivery, System/Sterilisation, ISO Testing and Pre-Clinical Testing.
A business plan and commercialisation plan have also been developed for the implementation of the project.
Phase 1 has shown that the concept is technically and commercially viable and a Phase 2 application is now being developed.
1. Validation of the modifications to existing stents as a way forward
Commercially available stents were technically evaluated to assess the capability of modification with a spiral laminar flow inducer. The results demonstrated the ability to create Spiral Laminar Flow and showed that the stent design will need to be customised to meet the performance requirements. A full testing plan (in accordance with the relevant ISO) has been produced for Phase 2.
2. Assess stent covering to see how this will affect the stent
Covered and uncovered stents were modified to determine the effect of stent covering. Mechanical tests assessed whether the covering adversely effects the structure, pliability and expected function of the stent. This allowed us to determine that modification of pre-existing stents is a technically viable option.
3. Determine the nitinol stent patent landscape and additional IP regime
Intellectual property searches were conducted to determine whether patents exist that have claimed the use of nitinol to modify blood flow through medical devices. This indicated that we have freedom to operate in this area. The company has potential to file new Patents in Phase 2 development to strengthen the current 17 Patent families in the Patent estate. The company has a further approved Trademark SLF* which describes the design platform.
4. Identify partners for manufacture and commercialization
We identified and engaged sufficient numbers of relevant, interested parties to participate in the manufacturing and route to market process. These potential partners can provide commercial services, quotations and appropriate lead-times. Parties identified were categorised into the following groups: Metal Stent Manufacture, ePTFE Covering, Assembly/Delivery, System/Sterilisation, ISO Testing and Pre-Clinical Testing.
A business plan and commercialisation plan have also been developed for the implementation of the project.
Phase 1 has shown that the concept is technically and commercially viable and a Phase 2 application is now being developed.
Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti
Task 1: Validation of incorporating SLF inducer into existing stents
This task details the testing activities undertaken on proof of concept Self-Expanding Nitinol Peripheral Stents incorporating a Spiral Flow Inducing Ridge.
The main purpose of the tests was to enable a decision as to whether the development of a stent incorporating spiral laminar flow can be achieved by modifying an existing stent or whether VFT should embark on a programme to design and manufacture a unique stent incorporating SLF.
I. Scope
This task was specific to the products listed in Table 1. Table 2 shows the tests carried out.
Table 1: Product References
Product Code: Optimed/Creamedix
Proof of Concept #1
Description: Spiral Laminar Flow Stent 8 x 70mm
Product Code: Optimed/Creamedix
Proof of Concept #2
Description: Spiral Laminar Flow Stent 8 x 110mm Stent Design: Planis Modified rev.29
Table 2: Associated Document References (available on request)
T014-R Partially covered spiral stent first (acute) animal study
T015-R Partially covered spiral stent pre-clinical Thiel cadaver study
T016-R Partially covered spiral stent flow testing
T017-R Spiral stent coating and flow testing
T021-P Spiral Laminar Flow Stent Development Test Plan
Test Articles
Product Code: Optimed/Creamedix
Proof of Concept #1
Description: Spiral Laminar Flow Stent 8 x 70mm
Stent design based on Optimed Sinus Stent
Product Code: Optimed/Creamedix
Proof of Concept #2
Description: Spiral Laminar Flow Stent 8 x 110mm Stent Design: Planis Modified rev.29
Lot : EW- 2014-205 #1 to EW– 2014 -205 #4
Stent design based on Optimed Sinus Flex Stent
II. Test Summary and Discussion
T017 Spiral stent coating and flow testing (Proof of concept design #1)
The prototype spiral stent (based on an Optimed Stent with closed cell diamond pattern) was successfully modified (using a heat/mechanical deformation process) to incorporate the P3 Ridge Profile as used on the current range of commercially available ePTFE Vascular Grafts. The stent supplied was uncovered and was successfully coated with latex rubber to create the spiral laminar flow fin (an uncovered stent of this design will only create turbulence). A single spiral flow was found in the outflow of the device using colour Doppler and vector Doppler ultrasound imaging. The non uniform nature of this single spiral has been associated with the abrupt termination of the spiral ridge at the end of the stent. This issue will be factored into Proof of Concept design #2.
In addition to verification of Spiral Laminar Flow this testing supports:
T021-P Spiral Laminar Flow Stent Development Test Plan
• Test 1: Visual Inspection and dimensional verification
T016 Partially covered spiral stent flow testing (Proof of concept design #2)
The prototype spiral stent (based on an Optimed Sinus Flex Stent with open cell ring and strut pattern) was successfully modified (using a heat/mechanical deformation process) to incorporate the P3 Ridge Profile as used on the current range of commercially available ePTFE Vascular Grafts. In addition to the change of basic stent design, the inducer ridge was modified at either end to replicate the run in/run out as feature on the graft design. This stent has been further modified to include an ePTFE covering along the length of the flow inducer ridge. This covering process requires further investigation/optimisation/development.
The flow was tested in both ends of the spiral stent after reversion of the flow direction. One strut in one end of the spiral stent was broken.
The non-broken strut end was able to create a uniform and steady single spiral flow. A steady single spiral started to be observed at 3.5 cm after the stent inlet and was completely formed 6.5 cm distal from the stent inlet. This information will be used in future design efforts to decrease the length of the spiral ridge and consequently the overall length of the device.
The flow disturbance at the top side of the colour Doppler images from the broken strut end has been directly associated with the damaged strut. Flow disturbances at the end of the stent seen on POC #1 have been resolved on this prototype due to the incorporation of run in and run out geometry at the end of the ridge.
The partially covered spiral stent was able to induce a steady single spiral flow in both ends.
In addition to verification of Spiral Laminar Flow this testing supports:
T021-P Spiral Laminar Flow Stent Development Test Plan
• Test 1: Visual Inspection and dimensional verification
• Test 12: Vessel wall apposition
• Test 17: Compatibility of parts
• Test 18: Stent Deployment Force
• Test 19: Trackability and Pushability
• Test 20: Simulated use
T015 Partially covered spiral stent pre-clinical Thiel cadaver study (Proof of concept design #2)
The prototype spiral stent (based on an Optimed Sinus Flex Stent with open cell ring and strut pattern) was successfully modified (using a heat/mechanical deformation process) to incorporate the P3 Ridge Profile as used on the current range of commercially available ePTFE Vascular Grafts. In addition to the change of basic stent design, the inducer ridge was modified at either end to replicate the run in/run out as feature on the graft design. Stents were loaded in commercially available delivery catheters.
CONCLUSIONS
• Turbulent flow identified in vessel prior to any intervention
• Device delivered through vascular sheath into common femoral artery
• Deployed in mid CFA and expanded to full vessel diameter
• Expansion and location verified by X-Ray imaging
• Ultrasound assessment demonstrated spiral ridge intact
• Colour flow demonstrated spiral flow within device and propagation up to 5 cm downstream of device.
In addition to verification of Spiral Laminar Flow this testing supports:
T021-P Spiral Laminar Flow Stent Development Test Plan
• Test 1: Visual Inspection and dimensional verification
• Test 12: Vessel wall apposition
• Test 17: Compatibility of parts
• Test 18: Stent Deployment Force
• Test 19: Trackability & Pushability
• Test 20: Simulated use
• Test 21: X-Ray Visibility
T014 Partially covered spiral stent first (acute) animal study (Proof of concept design #2)
The prototype spiral stent (based on an Optimed Sinus Flex Stent with open cell ring and strut pattern) was successfully modified (using a heat/mechanical deformation process) to incorporate the P3 Ridge Profile as used on the current range of commercially available ePTFE Vascular Grafts. In addition to the change of basic stent design, the inducer ridge was modified at either end to replicate the run in/run out as featured on the graft design. Stents were loaded in commercially available delivery catheters.
In both animals the two SpiraStents were successfully deployed, although in one case the control stent was incorrectly deployed due to a misunderstanding regarding the positioning of radio-opaque markers.
A single spiral flow pattern was detected in the outflow of the SpiraStent and a disturbed flow pattern in the outflow of the control stent. There was no difficulty with stent deployments and with using the deploying devices. The inconsistencies regarding the radio-opaque markers will need to be addressed prior to future studies.
In addition to verification of Spiral Laminar Flow this testing supports:
T021-P Spiral Laminar Flow Stent Development Test Plan
• Test 1: Visual Inspection and dimensional verification
• Test 12: Vessel wall apposition
• Test 17: Compatibility of parts
• Test 18: Stent Deployment Force
• Test 19: Trackability and Pushability
• Test 20: Simulated use
• Test 21: X-Ray Visibility
CAD Evaluation
In order to evaluate whether it is technically possible to develop and manufacture a stent incorporating spiral flow either by altering the physical geometry of an existing stent design or developing a unique stent design, a series of Computer Aided Design (CAD) drawings were generated to evaluate the options.
Please see the PDF version of the final report for images
1. CAD Image of inducer ridge formed on Standard Optimed Sinus Flex Stent Design
2. CAD Image of Inducer ridge formed on Standard Cook Zilver Stent Design
It is clear from the CAD graphical representations of both standard stent designs that the deformation of the struts and connecting struts through the inducer ridge is irregular and non-uniform and without question would lead to damage and breakages during the rigorous fatigue testing that is required to be performed as part of the ISO 25539 guideline.
By modifying the existing stent design platforms as shown on the next two images such that the strut orientation is in alignment with the inducer path, it is clear that the deformation of struts and connecting struts through the inducer ridge is regular and uniform and would give a significantly higher performing stent during ISO fatigue testing.
Please see the PDF version of the final report for images
3. CAD Image of Modified generic open mesh stent design
4. CAD Image of Modified Cook Zilver stent design
III. Conclusion and Test Plan for Phase 2
The testing conducted in Task 1 has demonstrated clearly the ability to create Spiral Laminar Flow using a peripheral stent with geometry modifications to create an internal inducer ridge. It is clear that the stent design, whether based on an existing stent platform such as Optimed Sinus Flex or Cook Zilver (as examples) or of a unique VFT design, will have to be customised in order to accommodate the inducer ridge and meet the performance requirements set out in ISO 25539.
In addition to this, several of the characterisation tests as detailed in the Spiral Laminar Flow Stent Development Test Plan have been met, demonstrating that the basic performance parameters of a modified Spiral Flow stent are achievable.
A full testing plan, which will be undertaken within Phase 2 of the SpiraStent Product Development, has now been fully detailed in T021. This testing, which will be conducted in accordance with the relevant ISO standards, will be initiated post design freeze as the testing represents a significant commitment in timescale, resource and cost.
In addition to the ISO testing detailed in T021, FEA (Finite Elemental Analysis) will be conducted on late stage designs prior to a design freeze in order to validate the final stent design, specification and material properties.
Task 2: Intellectual property landscape
Task 2 involved a thorough understanding of the IP landscape and the 3 activities were:
1. Conduct IP searches to determine existing IP rights (patents, trademarks, designs) regarding nitinol self-expanding stents to determine freedom to operate.
2. Examine VFT’s existing patents to determine opportunities for development.
3. Determine novel and patentable features of SpiraStent and opportunities for exploitation.
The output of task 2 is the integration of technology IP rights and commercialisation into company strategy.
The SpiraStent product development strategy calls for the design and modification of an existing nitinol stent frame structure, using proprietary methods, techniques and know how within the company. The next stages in development and in manufacture are covering, loading onto a delivery system and packaging and sterilisation.
Actions and outputs
VFT’s patent estate now consists of 17 patent families and their foreign equivalents. To date five UK patents, five European patents and four US patent grants have been obtained. In addition five US and six European design patents have been granted. The inventive step, and the key to the VFT scientific platform, is the design ability to induce the required spiral flow in a specific application that will have the beneficial effects of reducing turbulence. This principal patent and subsequent research have resulted in the broadening of the patent portfolio.
Patent Attorneys Marks and Clerk were commissioned to undertake a comprehensive Freedom to Operate search of the Covered Stent arena to enable a strong understanding of the existing IP landscape. The general idea of a nitinol frame with a cover of PTFE appears to have been disclosed some time ago, so there do not appear to be specific incidents of clear cut infringement. However there are a number of potential claims which will steer cover material and design.
These will be addressed as follows:
• Nitinol frame design The product development plan and manufacturing plan includes a license and development agreement with Optimed GmbH and an ongoing material supply agreement. This agreement effectively licenses the design IP for the ‘master stent’ design from Optimed and avoids potential conflict on this stent design platform which in turn avoids infringement of any other stents on the market.
• Covering The FTO analysis revealed a number of potential areas of caution . There are a few additional patents with very specific claims which M+C have considered as more remote claims. Each of the claims will be considered in detail in collaboration with the cover material supplier (Zeus Inc) and the SpiraStent product claims modified to avoid infringement. Initial review indicates the patents highlighted in the FTO are not claims which will affect our development.
• Delivery system The stent loading and delivery system will be supplied by Optimed GmbH and as such we will be indemnified from any IP challenge through the license and development and supply agreement.
• IP development The company has potential to file new Patents in a number of areas of Phase 2 development enabling a further strengthening of the current 17 Patent families that comprise the Patent estate. In addition the company has an approved Trademark SLF* which describes the design platform.
Patent family 18 will be filed during Phase 2 and will focus on the method of modification and manufacture. The innovative step has been lodged with M+C in November 2014 and the Patent Attorneys and internal team are in the process of Patent draft.
Further IP development is possible in collaboration with Optimed GmbH with regards to modification of the delivery system. At key stages of Phase 2 and during project plan review gates, a formal IP review will be conducted by the project team to assess potential for further IP development.
Summary
Task 2 required an IP landscape review with a focus on FTO and examination of the existing patent portfolio for potential development with a view to new IP. This task has concluded that there is freedom to operate and highlights additional areas for further patent applications in the Phase 2 project.
Regular IP reviews take place within the company as part of the Management Review process within the scope of the ISO 13485 Standard. The next phase development will implement further IP reviews at each stage gate project review.
VFT has 17 existing Patent families, a group of Trademarks and a growing body of ‘know how’ and these Intellectual Property assets form the commercial foundation of the company.
The company has completed these tasks in line with the business plan and product development strategy and is ready to embark on Horizon 2020 Phase 2 development.
Task 3: Partner identification
The objective of the partner identification is to identify and engage relevant interested parties such as manufacturers and clinical testing providers who are willing to participate in production and validation of SpiraStent during Phase 2 of the project.
VFT has identified and engaged specific, relevant and industry leading parties to participate in the manufacturing and route to market process. These sub-contractors are in position to provide commercial services, quotations and appropriate lead-times.
Parties identified were categorised into a number of groups:
• Metal Stent Manufacture
• ePTFE Covering
• Assembly/Delivery System/Sterilisation
• ISO Testing
• Pre-Clinical Testing
Partner identifi
cation
Metal Stent Manufacture
Creamedix GmbH
Germany
www.creamedix.eu
Creamedix GmbH is a European SME with a strong history in rapid product development. Incorporated in 2007, the firm specialises in high precision and quality using laser technology, such as fibre and femtolaser. It produces micro structures with highest precision through cutting, drilling and welding of nitinol, CoCr or stainless steel.
Relevance: VFT has developed a working relationship with this company in the area of metal stent manufacture. Creamedix has a dedicated R&D and manufacturing team with expertise in product and process design and optimisation. The firm has access to existing stent platform avoiding IP infringement issues.
Manufacturing Strategy
Pera Technology
www.peratechnology.com
Established in 1946, Pera Technology was originally the Production and Engineering Research Association and is now an established new product development contractor. The traditional engineering capability within Pera is still a particular strength making the firm well placed to advice and help with the manufacturing strategy for SpiraStent. Pera also has a wealth of experience with helping and advising clients as part of Horizon 20:20 grants.
Relevance: Pera Technology will use its engineering expertise to develop a comprehensive and robust manufacturing strategy that will cover the ability of VFT to take the technology to modify a standard stent to incorporate a SLF inducer fin. The strategy will cover tooling specifications and the plans to scale modification for manufacture. Pera may also undertake some bench testing of prototype modified stents to enable decisions to be quickly made about progression of particular designs of stents.
ePTFE Covering
Zeus Ireland
Ireland
www.zeusinc.com
Established in 1966, Zeus is a global large enterprise involved in the manufacture of precision polymer extrusions. Its extruded tubing products include Teflon tubing, nylon, Pebax, Grilamid, coextrusions, multilumen, bump tubing, layflat tubing, dual tube, spiral cut tubing and convoluted tubing. The company also manufactures a variety of heat shrinkable tubing and monofilaments. Zeus products are used in the medical, fluid handling, electrical and mechanical markets.
Relevance: VFT has developed a working relationship with Zeus in the area of ePTFE/polymer covering. The company’s European operations are based in Ireland with access to broader product technologies from Zeus Inc. It has a dedicated R&D and manufacturing team available in Ireland. Zeus has developed a novel material specifically for use as a high performance, low profile stent covering. The material avoids issues surrounding the "Goldfarb" patent assigned to CR Bard (USA).
Assembly / Delivery System / Sterilisation
OptiMed Medizinische Instrumente GmbH
Germany
www.opti-med.de
OptiMed Medizinische Instrumente GmbH is a European SME. Established in 1996, this company’s core competences lie in the development, manufacture, assembly, packaging and sterilisation of catheter delivery systems. Optimed boasts proven stent design platform using the sinus flex stent and associated delivery systems.
Relevance: VFT has developed a working relationship with this company in the area of assembly/delivery system/sterilisation. Optimed has a dedicated R&D and manufacturing team. The European based operation has a strong product portfolio within the stent and catheter field together with proven stent design platform using the Sinus Flex Stent.
ISO Testing
PROTOMED SA
France
www.protomedlabs.com
PROTOMED SA is a European based SME with ISO9001 and ISO13485 accreditation and history of single source medical device testing to ISO, ASTM and EN standards. This company is recognised as a leading provider of turnkey device testing specifically in the area of peripheral stents.
Relevance: VFT has developed a working relationship with PROTOMED in the area of ISO testing.
Pre-Clinical Testing
University of Utrecht
Netherlands
www.uu.nl
Established in 1636, the University of Utrecht is one of the oldest universities in the Netherlands and one of the largest in Europe.
Relevance: VFT has an existing working relationship with the University of Utrecht in the area of pre-clinical testing. Previously, VFT has utilised the services of Utrecht in its product developments. Trials were conducted under "ethics approval" following standard GLP protocols by appropriately trained personnel in conjunction with VFT engineers to evaluate Colour Doppler Imaging.
Vascular Flow Technologies will be involved in the Assembly/Delivery/System and Pre-Clinical Trial Testing tasks. VFT core competences lie in the development, manufacture, testing and verification of Spiral Laminar Flow (SLF) medical devices, together with proving protection of intellectual property.
The sub-contractors identified in addition to Vascular Flow Technologies have demonstrated all the required skills, resources and expertise required for the development in the Phase 2 project.
Task 4: Business plan
Task 4 involved the development of a business plan for the SpiraStent technology with research and analysis into the following areas:
o Market opportunity
I. Market size, condition, growth, competitors, regulatory requirements
II. Market need / technology problem in the market and user group and user needs / the technological need
III. Solution offered by the project
o Business case and value proposition
I. Performance in the context of competition
II. Benefits for buyers and end-users, Value for operator / customer
III. Results of field trials
IV. Willingness to pay
o Technology description
I. Explanation of the technology principle
II. Competing research / developments
III. Performance of similar technologies
o Commercialisation strategy
I. Business opportunity around the technology
II. Commercialisation experience of the company in the sector
III. Commercialisation strategy including strategy for funding acquisition for funding gap after project end to ensure market introduction
IV. Risks and opportunities
V. Route to Market
VI. Marketing Plan
o IPR Strategy
I. Options for IPR protection of the commercial opportunity, FTO and IPR strategy
o Financial Projections
I. Profit and Loss, Cashflow, Balance Sheet – Historic and projected to 5 years
The results of all of this work can be seen in the Business Plan document (available on request) which is one of the outputs of this project. A summary of each section is included in the following pages.
Market Opportunity
The global peripheral vascular stent market was worth $2.16B in 2012 with a CAGR of 8%. The market is dominated by Cook Medical, WL Gore and Abbott Vascular which hold 42% of the market between them. However, a differentiated product has the opportunity to gain a significant niche market and currently 21% of the market is held by minority players.
Please see the PDF version of the final report for a table that provides an overview of the peripheral vascular stent market from 2012. This information as well as the subsequent graphs have been taken from the report “Peripheral Vascular Stents: Global Analysis and Market Forecasts” by Medipoint published in April 2013. This market is growing at an average of 8% CAGR.
2012 Peripheral Vascular Stent Market Sales
Please see the PDF version of the final report for this table
There are a number of interesting points in relation to this market.
(1) The market size is significant so even a small share can be extremely profitable.
(2) The market size will continue to grow. Although smoking is likely to decrease as a primary factor as legislation and cost reduce its popularity, both diabetes and average population age are on the increase.
(3) Although the US market appears much larger than the EU, this is primarily due to the average costs of the device which are much higher in North America (Global Data market research).
(4) The market is still dominated by Bare Metal Stents. VFT are designing both Bare Metal Stents and Covered Stents for this project. The design will be identical except for the coating.
Peripheral artery disease (PAD) affects approximately 10 million adults in the USA alone (Stoppler, 2012). It is a disease of the arteries outside the heart and brain that can lead to the loss of a limb and be life-threatening. Peripheral arterial disease (PAD) is one of the fastest-growing and most pervasive diseases, and it is estimated to affect 27m individuals in Europe and North America of which 10.5m are symptomatic and 16.5m asymptomatic.
Business Case and Value Proposition
The main competition to the SpiraStent product are other stents since the other treatment options are relevant to different stages of the disease progression. There are four types of stent available:
• Bare Metal Stents
• Drug Eluting Stents
• Covered Stents
• Bioabsorbable Stents
Bare metal stents consist of bare metal open mesh-like tubes to provide a mechanical means of resisting recoil of the artery. They do not prevent (and may to a certain extent even cause) another failure mode known as restenosis. Restenosis is a reclosure of the treatment site through the open mesh of the stent caused by local injury and a subsequent tissue response. Drug eluting stents have offered the promise of reduction of stent restenosis. However, the extension of the coronary experience of successful reduction in restenosis (Sirius , Ravel and Taxus IV trials) has not been demonstrated in early application to femoropopliteal disease.
More recently covered stents have been developed which incorporate a polymer film which prevents tissue from prolapsing or growing through the open mesh of the stent. Bioabsorbable stents are created from materials that will gradually absorb into the body and degrade over time. These are used to provide a temporary scaffold for up to a year before losing their mechanical strength.
The market is dominated by bare metal stents and covered stents with drug-eluting stents and bioabsorbable stents having a very minor share of the market.
The primary benefit of the SpiraStent device is that it re-introduces spiral blood flow into the circulatory system downstream from the stent. This has been shown in the VFT graft products to lead to an increase in patency of the graft. The benefits of increased patency are decreased patient morbidity and a reduction in the number of re-implantations. The SpiraStent device has not yet been used in clinical trials although some very encouraging clinical evidence has been demonstrated from the use of the two VFT graft products, summarised in the following two tables.
Please see the PDF version of the final report for these tables
The demand for stent options for PAD is large and growing at a CAGR of 8%. The sales price varies greatly from country to country and between stent types.
Country: USA
Bare Metal Stent: $1300
Covered Stent: $3000
Drug Eluting Stent: $2200
Bioabsorbable Stent: $3400
Country: EU (France, Germany, Italy, Spain, UK)
Bare Metal Stent: $600
Covered Stent: $1200
Drug Eluting Stent: $800
Bioabsorbable Stent: $3400
Country: Japan
Bare Metal Stent: $2347
Covered Stent: $3410
Drug Eluting Stent: $4200
Bioabsorbable Stent: $4760
Country: Brazil
Bare Metal Stent: $1200
Covered Stent: $2200
Drug Eluting Stent: $3000
Bioabsorbable Stent: $3400
Country: China
Bare Metal Stent: $1000
Covered Stent: $2400
Drug Eluting Stent: $1700
Bioabsorbable Stent: $3600
Country: India
Bare Metal Stent: $700
Covered Stent: $2200
Drug Eluting Stent: $1700
Bioabsorbable Stent: $3600
As can be seen above, the EU market prices are considerably lower (apart from in regards to bioabsorbable stents) than the ROW. This depresses the overall market size in the EU although the number of operations will be comparable to the USA.
Technology Description
The SpiraStent project will develop a self-expanding stent comprising a nitinol stent that incorporates an integral spiral flow inducer fin. The entire stent including the fin is covered both internally and externally with a polymer covering. The stent will be capable of being deployed using a standard “over the wire” delivery system that releases the stent by way of a pull-back outer 7-8F sheath. SpiraStent will reintroduce the blood’s normal spiral laminar flow both through the stent and downstream to the stent, which will in turn reduces the laterally directed forces and turbulence and therefore lowers the rates of distal disease progression. Additionally the stent will be designed to produce lower stresses to the vascular wall at the distal end to prevent distal junctional stenosis.
Whilst a strong knowledge and technology base exists underlying the SpiraStent concept, specific new knowledge and technology breakthroughs are required in the following areas:
• Spiral flow inducer: whilst an inducer has been developed demonstrating the benefits of spiral flow in a graft, little knowledge exists on how the optimal geometrical design parameters of a stent will influence the hemodynamic factors creating the spiral laminar flow within and downstream of the implanted stent;
• Stent design: whilst standard self-expanding stent design is fairly well understood, no knowledge exists on the design of a stent incorporating a flow inducer and how this will affect the way in which the spiral flow inducer is deployed as the stent expands and the radial forces are exerted on the vessel. Further development is required in designing a stent with lower radial forces at the distal end;
• Stent cover: whilst stents have been covered using a range of polymeric materials it is known that these are susceptible to tears which presently does not prove to be detrimental but would affect the spiral flow properties. PTFE is the material of choice. Further development work is required to select the optimal specification.
• Integrated stent and delivery system: self-expanding stents have been delivered using over the wire methods, however the way the flow inducer expands and the effects of the compression on the self-expansion of the fin after deployment is not fully understood.
Commercialisation strategy
VFT plans to sell the stent through its current market channels which consist of a mix of distributors and direct sales. Since the SpiraStent product will be sold to a similar clinical market, these initial products will act as trailblazers and SpiraStent will continue to develop VFT’s growing reputation in this sector.
The SpiraStent product is addressing a much larger market opportunity and as such has the potential to bring large revenues into the company. The concept behind spiral flow has been shown in the current products which have demonstrated very strong medical evidence for their use over competing grafts due to improved long term patency. This results in less interventions and the associated improvement in quality of life.
IPR Strategy
VFT has developed and protected 17 patent families relating to spiral flow that protect its USPs and possible future enhancements. This IP space is well established and defendable.
For the basic stent design, the preferred option is to partner with an established stent company with an IP portfolio and use its design as the basis for SpiraStent. This partnering will be based on a license to use paying a fixed percentage per stent sold. Whilst this will reduce the commercial margin it will also decrease the risk, development time and development cost. Since the chosen basic stent for modification will already be CE marked this should also decrease the regulatory burden on the company.
Financial Projections
The table given within the PDF report version shows the P/L for the SpiraStent product based on moderate sales figures. As with any new medical product, the initial sales are low into this very conservative market until the clinical proof b
egins to be publ
This task details the testing activities undertaken on proof of concept Self-Expanding Nitinol Peripheral Stents incorporating a Spiral Flow Inducing Ridge.
The main purpose of the tests was to enable a decision as to whether the development of a stent incorporating spiral laminar flow can be achieved by modifying an existing stent or whether VFT should embark on a programme to design and manufacture a unique stent incorporating SLF.
I. Scope
This task was specific to the products listed in Table 1. Table 2 shows the tests carried out.
Table 1: Product References
Product Code: Optimed/Creamedix
Proof of Concept #1
Description: Spiral Laminar Flow Stent 8 x 70mm
Product Code: Optimed/Creamedix
Proof of Concept #2
Description: Spiral Laminar Flow Stent 8 x 110mm Stent Design: Planis Modified rev.29
Table 2: Associated Document References (available on request)
T014-R Partially covered spiral stent first (acute) animal study
T015-R Partially covered spiral stent pre-clinical Thiel cadaver study
T016-R Partially covered spiral stent flow testing
T017-R Spiral stent coating and flow testing
T021-P Spiral Laminar Flow Stent Development Test Plan
Test Articles
Product Code: Optimed/Creamedix
Proof of Concept #1
Description: Spiral Laminar Flow Stent 8 x 70mm
Stent design based on Optimed Sinus Stent
Product Code: Optimed/Creamedix
Proof of Concept #2
Description: Spiral Laminar Flow Stent 8 x 110mm Stent Design: Planis Modified rev.29
Lot : EW- 2014-205 #1 to EW– 2014 -205 #4
Stent design based on Optimed Sinus Flex Stent
II. Test Summary and Discussion
T017 Spiral stent coating and flow testing (Proof of concept design #1)
The prototype spiral stent (based on an Optimed Stent with closed cell diamond pattern) was successfully modified (using a heat/mechanical deformation process) to incorporate the P3 Ridge Profile as used on the current range of commercially available ePTFE Vascular Grafts. The stent supplied was uncovered and was successfully coated with latex rubber to create the spiral laminar flow fin (an uncovered stent of this design will only create turbulence). A single spiral flow was found in the outflow of the device using colour Doppler and vector Doppler ultrasound imaging. The non uniform nature of this single spiral has been associated with the abrupt termination of the spiral ridge at the end of the stent. This issue will be factored into Proof of Concept design #2.
In addition to verification of Spiral Laminar Flow this testing supports:
T021-P Spiral Laminar Flow Stent Development Test Plan
• Test 1: Visual Inspection and dimensional verification
T016 Partially covered spiral stent flow testing (Proof of concept design #2)
The prototype spiral stent (based on an Optimed Sinus Flex Stent with open cell ring and strut pattern) was successfully modified (using a heat/mechanical deformation process) to incorporate the P3 Ridge Profile as used on the current range of commercially available ePTFE Vascular Grafts. In addition to the change of basic stent design, the inducer ridge was modified at either end to replicate the run in/run out as feature on the graft design. This stent has been further modified to include an ePTFE covering along the length of the flow inducer ridge. This covering process requires further investigation/optimisation/development.
The flow was tested in both ends of the spiral stent after reversion of the flow direction. One strut in one end of the spiral stent was broken.
The non-broken strut end was able to create a uniform and steady single spiral flow. A steady single spiral started to be observed at 3.5 cm after the stent inlet and was completely formed 6.5 cm distal from the stent inlet. This information will be used in future design efforts to decrease the length of the spiral ridge and consequently the overall length of the device.
The flow disturbance at the top side of the colour Doppler images from the broken strut end has been directly associated with the damaged strut. Flow disturbances at the end of the stent seen on POC #1 have been resolved on this prototype due to the incorporation of run in and run out geometry at the end of the ridge.
The partially covered spiral stent was able to induce a steady single spiral flow in both ends.
In addition to verification of Spiral Laminar Flow this testing supports:
T021-P Spiral Laminar Flow Stent Development Test Plan
• Test 1: Visual Inspection and dimensional verification
• Test 12: Vessel wall apposition
• Test 17: Compatibility of parts
• Test 18: Stent Deployment Force
• Test 19: Trackability and Pushability
• Test 20: Simulated use
T015 Partially covered spiral stent pre-clinical Thiel cadaver study (Proof of concept design #2)
The prototype spiral stent (based on an Optimed Sinus Flex Stent with open cell ring and strut pattern) was successfully modified (using a heat/mechanical deformation process) to incorporate the P3 Ridge Profile as used on the current range of commercially available ePTFE Vascular Grafts. In addition to the change of basic stent design, the inducer ridge was modified at either end to replicate the run in/run out as feature on the graft design. Stents were loaded in commercially available delivery catheters.
CONCLUSIONS
• Turbulent flow identified in vessel prior to any intervention
• Device delivered through vascular sheath into common femoral artery
• Deployed in mid CFA and expanded to full vessel diameter
• Expansion and location verified by X-Ray imaging
• Ultrasound assessment demonstrated spiral ridge intact
• Colour flow demonstrated spiral flow within device and propagation up to 5 cm downstream of device.
In addition to verification of Spiral Laminar Flow this testing supports:
T021-P Spiral Laminar Flow Stent Development Test Plan
• Test 1: Visual Inspection and dimensional verification
• Test 12: Vessel wall apposition
• Test 17: Compatibility of parts
• Test 18: Stent Deployment Force
• Test 19: Trackability & Pushability
• Test 20: Simulated use
• Test 21: X-Ray Visibility
T014 Partially covered spiral stent first (acute) animal study (Proof of concept design #2)
The prototype spiral stent (based on an Optimed Sinus Flex Stent with open cell ring and strut pattern) was successfully modified (using a heat/mechanical deformation process) to incorporate the P3 Ridge Profile as used on the current range of commercially available ePTFE Vascular Grafts. In addition to the change of basic stent design, the inducer ridge was modified at either end to replicate the run in/run out as featured on the graft design. Stents were loaded in commercially available delivery catheters.
In both animals the two SpiraStents were successfully deployed, although in one case the control stent was incorrectly deployed due to a misunderstanding regarding the positioning of radio-opaque markers.
A single spiral flow pattern was detected in the outflow of the SpiraStent and a disturbed flow pattern in the outflow of the control stent. There was no difficulty with stent deployments and with using the deploying devices. The inconsistencies regarding the radio-opaque markers will need to be addressed prior to future studies.
In addition to verification of Spiral Laminar Flow this testing supports:
T021-P Spiral Laminar Flow Stent Development Test Plan
• Test 1: Visual Inspection and dimensional verification
• Test 12: Vessel wall apposition
• Test 17: Compatibility of parts
• Test 18: Stent Deployment Force
• Test 19: Trackability and Pushability
• Test 20: Simulated use
• Test 21: X-Ray Visibility
CAD Evaluation
In order to evaluate whether it is technically possible to develop and manufacture a stent incorporating spiral flow either by altering the physical geometry of an existing stent design or developing a unique stent design, a series of Computer Aided Design (CAD) drawings were generated to evaluate the options.
Please see the PDF version of the final report for images
1. CAD Image of inducer ridge formed on Standard Optimed Sinus Flex Stent Design
2. CAD Image of Inducer ridge formed on Standard Cook Zilver Stent Design
It is clear from the CAD graphical representations of both standard stent designs that the deformation of the struts and connecting struts through the inducer ridge is irregular and non-uniform and without question would lead to damage and breakages during the rigorous fatigue testing that is required to be performed as part of the ISO 25539 guideline.
By modifying the existing stent design platforms as shown on the next two images such that the strut orientation is in alignment with the inducer path, it is clear that the deformation of struts and connecting struts through the inducer ridge is regular and uniform and would give a significantly higher performing stent during ISO fatigue testing.
Please see the PDF version of the final report for images
3. CAD Image of Modified generic open mesh stent design
4. CAD Image of Modified Cook Zilver stent design
III. Conclusion and Test Plan for Phase 2
The testing conducted in Task 1 has demonstrated clearly the ability to create Spiral Laminar Flow using a peripheral stent with geometry modifications to create an internal inducer ridge. It is clear that the stent design, whether based on an existing stent platform such as Optimed Sinus Flex or Cook Zilver (as examples) or of a unique VFT design, will have to be customised in order to accommodate the inducer ridge and meet the performance requirements set out in ISO 25539.
In addition to this, several of the characterisation tests as detailed in the Spiral Laminar Flow Stent Development Test Plan have been met, demonstrating that the basic performance parameters of a modified Spiral Flow stent are achievable.
A full testing plan, which will be undertaken within Phase 2 of the SpiraStent Product Development, has now been fully detailed in T021. This testing, which will be conducted in accordance with the relevant ISO standards, will be initiated post design freeze as the testing represents a significant commitment in timescale, resource and cost.
In addition to the ISO testing detailed in T021, FEA (Finite Elemental Analysis) will be conducted on late stage designs prior to a design freeze in order to validate the final stent design, specification and material properties.
Task 2: Intellectual property landscape
Task 2 involved a thorough understanding of the IP landscape and the 3 activities were:
1. Conduct IP searches to determine existing IP rights (patents, trademarks, designs) regarding nitinol self-expanding stents to determine freedom to operate.
2. Examine VFT’s existing patents to determine opportunities for development.
3. Determine novel and patentable features of SpiraStent and opportunities for exploitation.
The output of task 2 is the integration of technology IP rights and commercialisation into company strategy.
The SpiraStent product development strategy calls for the design and modification of an existing nitinol stent frame structure, using proprietary methods, techniques and know how within the company. The next stages in development and in manufacture are covering, loading onto a delivery system and packaging and sterilisation.
Actions and outputs
VFT’s patent estate now consists of 17 patent families and their foreign equivalents. To date five UK patents, five European patents and four US patent grants have been obtained. In addition five US and six European design patents have been granted. The inventive step, and the key to the VFT scientific platform, is the design ability to induce the required spiral flow in a specific application that will have the beneficial effects of reducing turbulence. This principal patent and subsequent research have resulted in the broadening of the patent portfolio.
Patent Attorneys Marks and Clerk were commissioned to undertake a comprehensive Freedom to Operate search of the Covered Stent arena to enable a strong understanding of the existing IP landscape. The general idea of a nitinol frame with a cover of PTFE appears to have been disclosed some time ago, so there do not appear to be specific incidents of clear cut infringement. However there are a number of potential claims which will steer cover material and design.
These will be addressed as follows:
• Nitinol frame design The product development plan and manufacturing plan includes a license and development agreement with Optimed GmbH and an ongoing material supply agreement. This agreement effectively licenses the design IP for the ‘master stent’ design from Optimed and avoids potential conflict on this stent design platform which in turn avoids infringement of any other stents on the market.
• Covering The FTO analysis revealed a number of potential areas of caution . There are a few additional patents with very specific claims which M+C have considered as more remote claims. Each of the claims will be considered in detail in collaboration with the cover material supplier (Zeus Inc) and the SpiraStent product claims modified to avoid infringement. Initial review indicates the patents highlighted in the FTO are not claims which will affect our development.
• Delivery system The stent loading and delivery system will be supplied by Optimed GmbH and as such we will be indemnified from any IP challenge through the license and development and supply agreement.
• IP development The company has potential to file new Patents in a number of areas of Phase 2 development enabling a further strengthening of the current 17 Patent families that comprise the Patent estate. In addition the company has an approved Trademark SLF* which describes the design platform.
Patent family 18 will be filed during Phase 2 and will focus on the method of modification and manufacture. The innovative step has been lodged with M+C in November 2014 and the Patent Attorneys and internal team are in the process of Patent draft.
Further IP development is possible in collaboration with Optimed GmbH with regards to modification of the delivery system. At key stages of Phase 2 and during project plan review gates, a formal IP review will be conducted by the project team to assess potential for further IP development.
Summary
Task 2 required an IP landscape review with a focus on FTO and examination of the existing patent portfolio for potential development with a view to new IP. This task has concluded that there is freedom to operate and highlights additional areas for further patent applications in the Phase 2 project.
Regular IP reviews take place within the company as part of the Management Review process within the scope of the ISO 13485 Standard. The next phase development will implement further IP reviews at each stage gate project review.
VFT has 17 existing Patent families, a group of Trademarks and a growing body of ‘know how’ and these Intellectual Property assets form the commercial foundation of the company.
The company has completed these tasks in line with the business plan and product development strategy and is ready to embark on Horizon 2020 Phase 2 development.
Task 3: Partner identification
The objective of the partner identification is to identify and engage relevant interested parties such as manufacturers and clinical testing providers who are willing to participate in production and validation of SpiraStent during Phase 2 of the project.
VFT has identified and engaged specific, relevant and industry leading parties to participate in the manufacturing and route to market process. These sub-contractors are in position to provide commercial services, quotations and appropriate lead-times.
Parties identified were categorised into a number of groups:
• Metal Stent Manufacture
• ePTFE Covering
• Assembly/Delivery System/Sterilisation
• ISO Testing
• Pre-Clinical Testing
Partner identifi
cation
Metal Stent Manufacture
Creamedix GmbH
Germany
www.creamedix.eu
Creamedix GmbH is a European SME with a strong history in rapid product development. Incorporated in 2007, the firm specialises in high precision and quality using laser technology, such as fibre and femtolaser. It produces micro structures with highest precision through cutting, drilling and welding of nitinol, CoCr or stainless steel.
Relevance: VFT has developed a working relationship with this company in the area of metal stent manufacture. Creamedix has a dedicated R&D and manufacturing team with expertise in product and process design and optimisation. The firm has access to existing stent platform avoiding IP infringement issues.
Manufacturing Strategy
Pera Technology
www.peratechnology.com
Established in 1946, Pera Technology was originally the Production and Engineering Research Association and is now an established new product development contractor. The traditional engineering capability within Pera is still a particular strength making the firm well placed to advice and help with the manufacturing strategy for SpiraStent. Pera also has a wealth of experience with helping and advising clients as part of Horizon 20:20 grants.
Relevance: Pera Technology will use its engineering expertise to develop a comprehensive and robust manufacturing strategy that will cover the ability of VFT to take the technology to modify a standard stent to incorporate a SLF inducer fin. The strategy will cover tooling specifications and the plans to scale modification for manufacture. Pera may also undertake some bench testing of prototype modified stents to enable decisions to be quickly made about progression of particular designs of stents.
ePTFE Covering
Zeus Ireland
Ireland
www.zeusinc.com
Established in 1966, Zeus is a global large enterprise involved in the manufacture of precision polymer extrusions. Its extruded tubing products include Teflon tubing, nylon, Pebax, Grilamid, coextrusions, multilumen, bump tubing, layflat tubing, dual tube, spiral cut tubing and convoluted tubing. The company also manufactures a variety of heat shrinkable tubing and monofilaments. Zeus products are used in the medical, fluid handling, electrical and mechanical markets.
Relevance: VFT has developed a working relationship with Zeus in the area of ePTFE/polymer covering. The company’s European operations are based in Ireland with access to broader product technologies from Zeus Inc. It has a dedicated R&D and manufacturing team available in Ireland. Zeus has developed a novel material specifically for use as a high performance, low profile stent covering. The material avoids issues surrounding the "Goldfarb" patent assigned to CR Bard (USA).
Assembly / Delivery System / Sterilisation
OptiMed Medizinische Instrumente GmbH
Germany
www.opti-med.de
OptiMed Medizinische Instrumente GmbH is a European SME. Established in 1996, this company’s core competences lie in the development, manufacture, assembly, packaging and sterilisation of catheter delivery systems. Optimed boasts proven stent design platform using the sinus flex stent and associated delivery systems.
Relevance: VFT has developed a working relationship with this company in the area of assembly/delivery system/sterilisation. Optimed has a dedicated R&D and manufacturing team. The European based operation has a strong product portfolio within the stent and catheter field together with proven stent design platform using the Sinus Flex Stent.
ISO Testing
PROTOMED SA
France
www.protomedlabs.com
PROTOMED SA is a European based SME with ISO9001 and ISO13485 accreditation and history of single source medical device testing to ISO, ASTM and EN standards. This company is recognised as a leading provider of turnkey device testing specifically in the area of peripheral stents.
Relevance: VFT has developed a working relationship with PROTOMED in the area of ISO testing.
Pre-Clinical Testing
University of Utrecht
Netherlands
www.uu.nl
Established in 1636, the University of Utrecht is one of the oldest universities in the Netherlands and one of the largest in Europe.
Relevance: VFT has an existing working relationship with the University of Utrecht in the area of pre-clinical testing. Previously, VFT has utilised the services of Utrecht in its product developments. Trials were conducted under "ethics approval" following standard GLP protocols by appropriately trained personnel in conjunction with VFT engineers to evaluate Colour Doppler Imaging.
Vascular Flow Technologies will be involved in the Assembly/Delivery/System and Pre-Clinical Trial Testing tasks. VFT core competences lie in the development, manufacture, testing and verification of Spiral Laminar Flow (SLF) medical devices, together with proving protection of intellectual property.
The sub-contractors identified in addition to Vascular Flow Technologies have demonstrated all the required skills, resources and expertise required for the development in the Phase 2 project.
Task 4: Business plan
Task 4 involved the development of a business plan for the SpiraStent technology with research and analysis into the following areas:
o Market opportunity
I. Market size, condition, growth, competitors, regulatory requirements
II. Market need / technology problem in the market and user group and user needs / the technological need
III. Solution offered by the project
o Business case and value proposition
I. Performance in the context of competition
II. Benefits for buyers and end-users, Value for operator / customer
III. Results of field trials
IV. Willingness to pay
o Technology description
I. Explanation of the technology principle
II. Competing research / developments
III. Performance of similar technologies
o Commercialisation strategy
I. Business opportunity around the technology
II. Commercialisation experience of the company in the sector
III. Commercialisation strategy including strategy for funding acquisition for funding gap after project end to ensure market introduction
IV. Risks and opportunities
V. Route to Market
VI. Marketing Plan
o IPR Strategy
I. Options for IPR protection of the commercial opportunity, FTO and IPR strategy
o Financial Projections
I. Profit and Loss, Cashflow, Balance Sheet – Historic and projected to 5 years
The results of all of this work can be seen in the Business Plan document (available on request) which is one of the outputs of this project. A summary of each section is included in the following pages.
Market Opportunity
The global peripheral vascular stent market was worth $2.16B in 2012 with a CAGR of 8%. The market is dominated by Cook Medical, WL Gore and Abbott Vascular which hold 42% of the market between them. However, a differentiated product has the opportunity to gain a significant niche market and currently 21% of the market is held by minority players.
Please see the PDF version of the final report for a table that provides an overview of the peripheral vascular stent market from 2012. This information as well as the subsequent graphs have been taken from the report “Peripheral Vascular Stents: Global Analysis and Market Forecasts” by Medipoint published in April 2013. This market is growing at an average of 8% CAGR.
2012 Peripheral Vascular Stent Market Sales
Please see the PDF version of the final report for this table
There are a number of interesting points in relation to this market.
(1) The market size is significant so even a small share can be extremely profitable.
(2) The market size will continue to grow. Although smoking is likely to decrease as a primary factor as legislation and cost reduce its popularity, both diabetes and average population age are on the increase.
(3) Although the US market appears much larger than the EU, this is primarily due to the average costs of the device which are much higher in North America (Global Data market research).
(4) The market is still dominated by Bare Metal Stents. VFT are designing both Bare Metal Stents and Covered Stents for this project. The design will be identical except for the coating.
Peripheral artery disease (PAD) affects approximately 10 million adults in the USA alone (Stoppler, 2012). It is a disease of the arteries outside the heart and brain that can lead to the loss of a limb and be life-threatening. Peripheral arterial disease (PAD) is one of the fastest-growing and most pervasive diseases, and it is estimated to affect 27m individuals in Europe and North America of which 10.5m are symptomatic and 16.5m asymptomatic.
Business Case and Value Proposition
The main competition to the SpiraStent product are other stents since the other treatment options are relevant to different stages of the disease progression. There are four types of stent available:
• Bare Metal Stents
• Drug Eluting Stents
• Covered Stents
• Bioabsorbable Stents
Bare metal stents consist of bare metal open mesh-like tubes to provide a mechanical means of resisting recoil of the artery. They do not prevent (and may to a certain extent even cause) another failure mode known as restenosis. Restenosis is a reclosure of the treatment site through the open mesh of the stent caused by local injury and a subsequent tissue response. Drug eluting stents have offered the promise of reduction of stent restenosis. However, the extension of the coronary experience of successful reduction in restenosis (Sirius , Ravel and Taxus IV trials) has not been demonstrated in early application to femoropopliteal disease.
More recently covered stents have been developed which incorporate a polymer film which prevents tissue from prolapsing or growing through the open mesh of the stent. Bioabsorbable stents are created from materials that will gradually absorb into the body and degrade over time. These are used to provide a temporary scaffold for up to a year before losing their mechanical strength.
The market is dominated by bare metal stents and covered stents with drug-eluting stents and bioabsorbable stents having a very minor share of the market.
The primary benefit of the SpiraStent device is that it re-introduces spiral blood flow into the circulatory system downstream from the stent. This has been shown in the VFT graft products to lead to an increase in patency of the graft. The benefits of increased patency are decreased patient morbidity and a reduction in the number of re-implantations. The SpiraStent device has not yet been used in clinical trials although some very encouraging clinical evidence has been demonstrated from the use of the two VFT graft products, summarised in the following two tables.
Please see the PDF version of the final report for these tables
The demand for stent options for PAD is large and growing at a CAGR of 8%. The sales price varies greatly from country to country and between stent types.
Country: USA
Bare Metal Stent: $1300
Covered Stent: $3000
Drug Eluting Stent: $2200
Bioabsorbable Stent: $3400
Country: EU (France, Germany, Italy, Spain, UK)
Bare Metal Stent: $600
Covered Stent: $1200
Drug Eluting Stent: $800
Bioabsorbable Stent: $3400
Country: Japan
Bare Metal Stent: $2347
Covered Stent: $3410
Drug Eluting Stent: $4200
Bioabsorbable Stent: $4760
Country: Brazil
Bare Metal Stent: $1200
Covered Stent: $2200
Drug Eluting Stent: $3000
Bioabsorbable Stent: $3400
Country: China
Bare Metal Stent: $1000
Covered Stent: $2400
Drug Eluting Stent: $1700
Bioabsorbable Stent: $3600
Country: India
Bare Metal Stent: $700
Covered Stent: $2200
Drug Eluting Stent: $1700
Bioabsorbable Stent: $3600
As can be seen above, the EU market prices are considerably lower (apart from in regards to bioabsorbable stents) than the ROW. This depresses the overall market size in the EU although the number of operations will be comparable to the USA.
Technology Description
The SpiraStent project will develop a self-expanding stent comprising a nitinol stent that incorporates an integral spiral flow inducer fin. The entire stent including the fin is covered both internally and externally with a polymer covering. The stent will be capable of being deployed using a standard “over the wire” delivery system that releases the stent by way of a pull-back outer 7-8F sheath. SpiraStent will reintroduce the blood’s normal spiral laminar flow both through the stent and downstream to the stent, which will in turn reduces the laterally directed forces and turbulence and therefore lowers the rates of distal disease progression. Additionally the stent will be designed to produce lower stresses to the vascular wall at the distal end to prevent distal junctional stenosis.
Whilst a strong knowledge and technology base exists underlying the SpiraStent concept, specific new knowledge and technology breakthroughs are required in the following areas:
• Spiral flow inducer: whilst an inducer has been developed demonstrating the benefits of spiral flow in a graft, little knowledge exists on how the optimal geometrical design parameters of a stent will influence the hemodynamic factors creating the spiral laminar flow within and downstream of the implanted stent;
• Stent design: whilst standard self-expanding stent design is fairly well understood, no knowledge exists on the design of a stent incorporating a flow inducer and how this will affect the way in which the spiral flow inducer is deployed as the stent expands and the radial forces are exerted on the vessel. Further development is required in designing a stent with lower radial forces at the distal end;
• Stent cover: whilst stents have been covered using a range of polymeric materials it is known that these are susceptible to tears which presently does not prove to be detrimental but would affect the spiral flow properties. PTFE is the material of choice. Further development work is required to select the optimal specification.
• Integrated stent and delivery system: self-expanding stents have been delivered using over the wire methods, however the way the flow inducer expands and the effects of the compression on the self-expansion of the fin after deployment is not fully understood.
Commercialisation strategy
VFT plans to sell the stent through its current market channels which consist of a mix of distributors and direct sales. Since the SpiraStent product will be sold to a similar clinical market, these initial products will act as trailblazers and SpiraStent will continue to develop VFT’s growing reputation in this sector.
The SpiraStent product is addressing a much larger market opportunity and as such has the potential to bring large revenues into the company. The concept behind spiral flow has been shown in the current products which have demonstrated very strong medical evidence for their use over competing grafts due to improved long term patency. This results in less interventions and the associated improvement in quality of life.
IPR Strategy
VFT has developed and protected 17 patent families relating to spiral flow that protect its USPs and possible future enhancements. This IP space is well established and defendable.
For the basic stent design, the preferred option is to partner with an established stent company with an IP portfolio and use its design as the basis for SpiraStent. This partnering will be based on a license to use paying a fixed percentage per stent sold. Whilst this will reduce the commercial margin it will also decrease the risk, development time and development cost. Since the chosen basic stent for modification will already be CE marked this should also decrease the regulatory burden on the company.
Financial Projections
The table given within the PDF report version shows the P/L for the SpiraStent product based on moderate sales figures. As with any new medical product, the initial sales are low into this very conservative market until the clinical proof b
egins to be publ
Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)
Peripheral arterial disease (PAD) is one of the fastest-growing and most pervasive diseases, and it is estimated to affect 27m individuals in Europe and North America of which 10.5m are symptomatic and 16.5m asymptomatic. Symptomatic PAD or intermittent caudation (IC) is usually diagnosed by a history of muscular leg pain when exercising and is relieved after a short period of resting. Vascular Flow Technologies has demonstrated with its two graft products that re-introducing spiral blood flow increases the patency of the product in the short and medium term. The SpiraStent project will develop a self-expanding stent that will reintroduce the bloods normal spiral laminar flow both through the stent and downstream to the stent, which will in turn reduces the laterally directed forces and turbulence and therefore lower the rates of distal disease progression.
The SpiraStent project will allow VFT to build on their SLF platform with an innovative stent design that improves outcomes for patients, reduces healthcare costs and will help grow the technical jobs market in the EU
The SpiraStent project will allow VFT to build on their SLF platform with an innovative stent design that improves outcomes for patients, reduces healthcare costs and will help grow the technical jobs market in the EU