One Valve For Life: The First Durable Non-Thrombotic Heart Valve Prosthesis

Project Information

TRIFLO

Grant agreement ID: 947344

DOI

10.3030/947344

Project closed

EC signature date 24 March 2020

Start date 1 April 2020

End date 31 July 2023

Funded under

• INDUSTRIAL LEADERSHIP - Innovation In SMEs

Total cost

€ 3 562 550,00

EU contribution

€ 2 493 785,00

Coordinated by

NOVOSTIA SA
Switzerland

Periodic Reporting for period 3 - TRIFLO (One Valve For Life: The First Durable Non-Thrombotic Heart Valve Prosthesis)

Reporting period: 2022-04-01 to 2023-07-31

Summary of the context and overall objectives of the project

Novostia is a medical device company incorporated in 2017 in the Canton of Neuchâtel (Switzerland) which aims at providing adults as well as young patients suffering from heart disease with a lifelong answer to their aortic and mitral valvulopathy: the TRIFLO valve. Valvular heart disease affects more than 100 million people worldwide. Every year more than 500.000 patients undergo a heart valve replacement. For patients younger than 65 years, valves currently available present serious constraints: either blood clot formation requiring lifelong problematic anticoagulation therapy with mechanical valves, or deterioration leading to replacement on average every 10 years with tissue valves. Therefore, cardiovascular surgeons are seeking a durable and non thrombogenic valve prosthesis. Thanks to a unique patented tri-leaflet design, which allows for optimal blood flow hemodynamics, and the use of a novel high-performance biocompatible material (PEEK), TRIFLO valve limits blood clot formation, while offering a lifelong durability. TRIFLO valve could thereby substantially improve the quality of life of millions of patients worldwide, whilst reducing overall healthcare costs. The current team at Novostia comprises all in all, employees, and strategic partners, about 150 experienced professionals in medical devices, quality and regulatory affairs, cardiovascular surgery, research, engineering, precision manufacturing, market access, fundraising, and business development. The EIC Accelerator grant, combined with €6.5M raised in 2018 and €2.5M raised in 2021 from private investors, has enabled the company to perform preclinical activities to launch the first phase of clinical studies, a fundamental step towards CE Marking, FDA Approval and China NMPA Approval, prerequisites for entering the market. To enter the market and expand its business, Novostia has considered three alternatives: signing distribution or even production license agreements with companies active in the medical devices sector; selling all or part of its activities to an already established multinational company that manufactures and sells heart valves; pursuing an autonomous development strategy as a new independent player and selling directly, through its own commercial distribution network or, indirectly, through regional distributors, the valves it would manufacture or subcontract to its current partners.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Within the frame of the EIC Accelerator, Novostia made tangible progress toward clinical studies and achieved 3 important milestones. All preclinical tests required to launch FIH which are the first phase of clinical studies have been successfully completed and documented in a thorough verification & validation (V&V) report. Based on the comprehensive results of the V&V activities, TRIFLO has demonstrated its safety and effectiveness for its intended use, meeting all necessary regulatory requirements. Novostia engineers and their academic, scientific, and industrial partners have developed and validated a manufacturing process that meets the highest quality and productivity standards. This manufacturing process is statistically capable (Cpk) and scalable. Several hundred units have already been manufactured for pre-clinical testing and clinical studies scheduled to start at the end of 2023. Thanks to a robust network of Swiss and French manufacturers, as well as top quality German and American suppliers of raw materials, Novostia will be able to satisfy the production needs that will increase sharply and rapidly with the start of the pivotal clinical study (800 patients-year) and even more so when the product is commercialized. On the medical scene, Novostia has succeeded in recruiting and mobilizing internationally renowned cardiac surgeons, haematologists and cardiologists. All are still active and have expressed their belief that a mechanical valve such as TRIFLO if it proves to be superior in terms of hemodynamics and thrombogenicity than current valves, should have its place in a market "stirred" by tissue prosthesis implanted via catheter (TVI). These cardiac surgeons will be the first prescribers of TRIFLO. Novostia has designed a clinical investigation plan for the FIH which aims at assessing the operational safety of the valve and at corroborating preliminary findings regarding its haemodynamics and efficacy. The FIH is designed to try reinforcing a key hypothesis for the clinical as well as commercial future of TRIFLO: its (low/non)-thrombogenicity. This first clinical phase shall include 10 patients who will be followed for 18 months at Vilnius University Hospital (Lithuania). The clinical investigation protocol, which has been approved by several high-caliber experts, has been designed to ensure maximum patient safety, a 100% success rate for implantation and a tight monitoring of the valve's function and behaviour. This protocol was approved by the Lithuanian authorities in August 2023. The first patient is expected to be implanted with a 21 mm valve placed in the aorta from December 2023. In addition to the grant awarded by the European Commission under the EIC Accelerator programme and the €6.5 million raised in 2018, Novostia has raised €2.5 million in 2021 from private investors and CHF 200,000 from the cantonal innovation promotion agencies. As a result, the company has been able to complete the activities required to launch the first phase of clinical trials (FIH), a key milestone on the road to CE marking and FDA and Chinese MNPA approvals, which are prerequisites for market entry. To kick-start the next round of fund-raising (Series B), Novostia has devised strategies for production, clinical trials, intellectual property protection and commercialization that should offer maximum chances of success for this groundbreaking technological project, which is set to serve a market worth tens of billions. Series B will be needed to finance phase II of the clinical trials, the Pilot Study, to develop larger sizes (23, 25 and 27 mm) and proprietary ancillaries.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

In the current standard-of-care, HVD is either treated by medication, valve repair or valve replacement.
In the last 20 years there has been significant activity in the field of heart valve prostheses, which has led to the development of animal tissue-based biological valves and optimized Transcatheter Valve Implantation (TVI) procedures. These advances, however, primarily address the needs of elderly patients only. As the long-term durability of biological valves remains an issue, younger patients (under 65 years, >30 million worldwide) still depend on mechanical valves and lifelong adherence to blood thinners as their main mode of treatment. In addition to biological valves, there has also been development in the field of polymeric valves and endogenous tissue regeneration technology. However, these innovations are still in early stages of development and will likely not reach the patient for another 10 years.
Beyond the state-of-the-art TRIFLO is the first valve prosthesis that is both durable and low/not-thrombogenic:
• TRIFLO has a unique proprietary three-leaflet design that effectively prevents formation of blood clots due to optimal hemodynamics.
• The TRIFLO valve is made of PEEK, a new biocompatible material that is extremely durable and ensures the lifetime of the valves.
• TRIFLO valve has a low acoustic signature thanks to both its unique design and high-tech material.

Figure 1: pictures of explanted valves after long term animal studies with no anti-coagulation