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Next Generation Flow Diverter for the Treatment of Intracranial Aneurysms Delivering Improved Patient Outcomes and Healthcare Cost Savings

Periodic Reporting for period 3 - OXIFLOW (Next Generation Flow Diverter for the Treatment of Intracranial Aneurysms Delivering Improved Patient Outcomes and Healthcare Cost Savings)

Période du rapport: 2023-01-01 au 2024-01-31

Intracranial aneurysms (IA’s) are a balloon like dilation on the arterial wall of the intracranial vasculature system. Under haemodynamic pressure, IA’s can grow and rupture leading to a subarachnoid haemorrhage (SAH). Each year ~51,000 EU citizens suffer a SAH, of whom 40% will die and a further 40% will suffer severe neurological disabilities requiring long-term social care. However, SAH’s are entirely avoidable through early intervention. Oxford Endovascular Ltd is developing a cure for brain aneurysms. The Project Team combines >100 years’ experience in the Med-tech sector, with >30 years direct clinical experience, and internationally renowned technical expertise in the development of novel endovascular devices using origami design principles.

Existing aneurysm treatment options include surgical clipping, an invasive procedure that, whilst delivering excellent long-term resolution, is an invasive, risky and expensive procedure with long patient recovery periods; and endovascular coiling, a minimally invasive procedure that, whilst lower risk, less expensive and with quicker patient recovery, delivers poorer long-term resolution. Neither techniques heal & remove the aneurysm and thus have the potential long-term symptoms and re-bleeding.

Flow diverters (FD’s) are a newer but established endovascular device that divert blood flow away from the aneurysm, thus eliminating the risk of growth/rupture and enabling natural healing. Whilst a promising excellent long-term resolution at lower risk and cost, existing FD’s have limitations inherent to their braided mesh design have uncontrolled and non-uniform radial forces, resulting in landing in the wrong position, poor opening and vessel apposition (areas prone to clot formation & creating stroke risk), variable porosity (poor flow dynamics) & device coning (causing migration).

OxiFlow is made from a shape memory nickel-titanium alloy and integrates origami design principles. The design combines an inner frame to address the placement and opening issues, with and outer sleeve to deal with the flow diversions and healing. The OxiFlow design enables optimum and uniform radial forces thereby overcoming the limitations of existing FDs. Furthermore, OxiFlow utilises an innovative delivery system that enables improved end user (doctor) control making the device easier and safer to place.

OxiFlow seeks to evaluate the safety and performance of the OxiFlow device through a 10- patient First-in-Human (FIH) clinical study. Project activities include device design freeze; transfer to and validation of pilot scale manufacture; pre-clinical verification and validation testing; GLP animal study; FIH study design and risk assessment; regulatory & ethical committee approvals; & FIH study implementation.
To date, much has been achieved to develop and test the technology in advance of a first in human (FIH) clinical study. Bench top testing of the flow diverter and delivery system has been conducted. The evaluation data from the key tests were used to support initial design of the device sizing that is suitable for animal studies. A functional performance study of the entire system was conducted. The data collected was used for further design improvements.

Specific device sizes have been transferred to pilot line manufacture. Process validation has prioritised device sizes that are critical to the animal studies and FIH clinical study. A plan outlining design verification and validation activities has been defined. Long lead time test sets have been prepared for. Tests either complete or being prepared for include but not exclusively:
• Durability (fatigue)
• Delivery System Tensile Bond Strength
• 2 years Accelerated Ageing (AA)
• Delivery System Dimensional Verification
• Biological Safety Assessment

A GLP animal study was undertaken for a first-generation design. This study evaluated the delivery and deployment of the stent and withdrawal of the delivery system. The deployments were easy to perform, with the implant showing good conformation to vessel wall. There were some indicators of improved performance over existing technologies such as accurate device placement, consistent opening and device conformity to the vessel walls. There were no device migrations suggesting that in clinical practice one may expect a reduced risk of the need to use multiple devices to treat a single aneurysm. Histology was normal. Aneurysm occlusion with aneurysm neck sizes of 3mm and below was as expected compared to competitive studies. Occlusion of wide-neck aneurysms (neck widths of >3mm) was slower than anticipated. Design modifications to address this have been completed (a more advanced dual layer, ‘Hybrid’ design). A formative user evaluation demonstrated that the device design enables easy and safe deployment of the stent into the target vessel location. Further animal studies have shown that the device is safe and effective with much better performance than the original design. A final GLP study is planned.
The development of a flow diverter technology and its delivery system that on the bench assessments and in-vivo animal models is suggesting improvements over existing technology.

Including:
• Maximised treatment outcomes with: i) Increased surgical success (reduced mortality and morbidity); ii) minimal long-term symptoms or impact on quality of life; and iii) Increased long-term efficacy: with a reduced chance of regrowth, rupture or need for reintervention.
• Minimises post-surgery pain and maximises recovery speed and return to work and normal life.
• A minimally invasive intervention with: i) Reduced risk of surgical complications; ii) Ease of use (vascular navigation and device deployment and placement); iii) greater utility (aneurysms difficult to treat with existing endovascular techniques); iv) Improved treatment efficacy and long-term patient outcomes; and v) minimal retraining.
• Improved healthcare efficiency: including surgical productivity and shorter patient recovery times.
• Reduced cost: by minimising devices used & increasing healthcare efficiencies & patient outcomes.

Our unique offering to market is still a next-generation F.D. design with:
• Optimum and uniform radial forces and porosity for improved vessel wall apposition, aneurysm occlusion and flow diversion, and device conformability (shape) and stability
• Enhanced flow diversion due to improved surface coverage (pore density)
• A unique delivery system enabling accurate placement and precise, predictable control of the device.

Our first in human data will be a key inflexion point that will give confidence to the device performance capability. Whilst more data will be required through a pivotal study to gain CE mark, the expected wider benefits will be more apparent. With Improved patient outcomes & healthcare delivery OxiFlow has the potential to reduce total mortality & morbidity by over 300 and 800 people respectively. We estimate social welfare cost savings of ~€240M and forecast a net gain of over €400M to the economy.
OXIFLOW Flow Diverter