Helping cancer survivors restoring their natural breast with resorbable implants inducing self‐tissue regeneration

Project Information

REGENERA

Grant agreement ID: 812002

DOI

10.3030/812002

Project closed

EC signature date 25 May 2018

Start date 1 June 2018

End date 31 December 2021

Funded under

• INDUSTRIAL LEADERSHIP - Innovation In SMEs

Total cost

€ 2 698 813,75

EU contribution

€ 1 889 169,63

Coordinated by

TENSIVE SRL
Italy

Periodic Reporting for period 3 - REGENERA (Helping cancer survivors restoring their natural breast with resorbable implants inducing self‐tissue regeneration)

Reporting period: 2020-08-01 to 2021-12-31

Summary of the context and overall objectives of the project

Tensive was founded in 2012 to address the challenge of developing advanced biomaterials for regenerative medicine. We are developing a bio-absorbable scaffold based on highly biocompatible polyurethane ester, which provides a biomimetic architecture that aims to promote blood vessels and soft tissue recruitment. Based on these unique properties, we will bring to the market REGENERA, an innovative breast prosthesis designed to be degraded over time and replaced by the patient´s soft tissue, with the goal to restore the aspect and natural feeling of the reconstructed breast.
Currently, the two most used methods for breast reconstruction are silicone implants and fat grafting. However, these methods have several limitations and associated complications, including the risk of rupture, capsular contracture, pain, and carcinogenic risks (including Anaplastic large cell lymphoma (ALCL)), among others, that lead to the need for multiple surgeries. REGENERA aims to address these problems, by developing a safe, customizable, minimal invasive solution for breast reconstruction that restores the shape of a natural breast. REGENERA will not require further surgeries, thus drastically reducing the pain, medical expenses, and psychological impact for the patients. Clinical validation will be required to demonstrate the estimated advantages/benefits.
The project objectives are (1) to conduct the first-in-human trial (FIH) of REGENERA and (2) to comply with the regulatory requirements needed for commercialization.

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

REGENERA project has been structured into 3 main pillars: (1) production and industrial process setup, (2) validation and (3) cross-functional activities. During the first reporting period, we obtained the following results:
- Production and Industrial Process Setup. The prototype was optimized to match the specifications requested by the target clinical application. Then, an upscaling study was conducted to adapt the process parameters to the increased production volumes requested for the industrial production line. All these parameters were defined, and a production line was developed and tested in compliance with the ISO 13485 and state-of-the-art Quality Control (QC) techniques for medical device production. The prostheses needed for the clinical trials were then produced according to the requested standards of Quality and to Medical Device Regulations.
- Validation. To achieve the clinical validation of our product through a single-center FIH clinical trial, all the required documentation was prepared and submitted to the competent authorities (the Italian Ministry of Health and the Hospital Ethical Committee). In October 2019 we received the approval to begin the study.
In addition, different cross-functional activities were carried out, such as communication and dissemination to create awareness about REGENERA. Finally, IP management has been carried out through the filing of a patent and working at the registration of REGENERA’s trademark.
During period 2, all the above-mentioned activities were carried forward with important achievements. The product formulation was further optimized based on the outcomes of the preclinical tests and the ongoing FIH clinical study. The production capacity was increased and the QC process was improved with the introduction of an additional biological test to better monitor the cytotoxicity.
Regarding the validation activities, a further preclinical test was started to evaluate the behavior and the performance of REGENERA in presence of oncological therapeutic treatments, i.e. radiotherapy and chemotherapy. The planned FIH study started.
In the third period, all the above activities have been completed. In particular, a determined number of scaffolds has been produced to supply the material needed for the FIH study and for pre-market activities. The technical advances have been included in a PCT patent application to protect the REGENERA device, its composition and the relevant manufacturing steps. The production line has been further optimized thanks to the validation of all the equipment involved in the process, through IQ/OQ and PQ validation.
The FIH clinical study has been completed and the results have been collected in two interim analyses, at 5 and 10 patients completed, respectively, and one final report. These results demonstrated the safety and tolerability of REGENERA as medical device to treat breast deformities following lumpectomy.
The preclinical validation of REGENERA has been integrated with a new study on murine model focused on effects of radio and chemotherapy on our scaffold, once implanted. The study showed no interaction of the scaffold with oncological treatments and promising results in terms of cell viability during and after the treatments. Moreover, the ISO13485 certification has been achieved by Tensive for the manufacturing of medical devices.
All Milestones have been achieved.

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)

The most common treatments for breast tissue defects present several risks and limitations:
- Gel-filled silicone implants: not lifetime devices with several complications, such as rupture (up to 30% incidence), capsular contracture, silicone leakage, and the risk of developing Anaplastic large cell lymphoma (ALCL), interference with breast imaging that detects recurrences, back/neck pain and spinal postural alterations due to their high weight, etc.
- Saline-filled silicone implants are used as an alternative to silicone gel-filled implants to decrease leakage problems. However, they also have complications and interfere with breast imaging.
- Fat grafting. This method is still limited to small volumes and represents a source of additional pain for the patients. In general, fat grafting is a very tedious, painful, physically demanding and time-consuming surgery, also presenting potential carcinogenic risks (in fact, its safety has not yet been demonstrated).
REGENERA’s unique design aims to promote vascularization, soft tissue recruitment and volume maintaining after implantation. These features are not present in the technologies currently available on the market. REGENERA is estimated to have substantial competitive advantages over alternative solutions, such as restoring the aspect and natural feeling of the reconstructed breast, decreased number of surgical interventions needed, decreased costs, elimination of implant-associated risks, no interference with breast imaging and overall improved quality of life. Clinical validation is required to demonstrate the estimated advantages/benefits.
Once on the market, we expect that REGENERA will have a significant impact on: (i) Healthcare system: saving the cost of additional surgeries (more than €200M yearly in the EU), contributing to the sustainability of the Healthcare system; (ii) Breast reconstruction patients: offering a solution to lumpectomy patients, for whom there are no optimal reconstructive options yet, and a better alternative for breast augmentation patients; a permanent solution by a minimal invasive procedure, that will improve patients’ quality of life; (iii) Company: increasing Tensive’s revenues (est. cumulative profit of ~€250M with an ROI of 19.37 by 2025); (iv) Society: benefiting many of the 735,000 women needing reconstructive surgery after breast cancer every year, together with the 1.65 million women yearly undergoing breast augmentation.

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