Periodic Reporting for period 2 - FibroFix Cartilage (FibroFix™ Cartilage, silk-based implant for cartilage repair and regeneration, introducing a new paradigm in osteoarthritis treatment.)
Période du rapport: 2021-07-01 au 2023-10-31
Cartilage deterioration and injuries often lead to osteoarthritis (OA) – a long-term chronic disease resulting in bones rubbing together and creating pain, stiffness and severe disability. Knee cartilage injuries are very common and almost half of them go on to develop OA, which is second only to heart disease as a cause of work disability. OA affects over 500million people globally (up to 10% of the global population).
Keyhole surgery to treat knee injury is the most common orthopaedic procedure. The majority involve removing damaged cartilage from either the shock absorbing meniscus or from the smooth, stiff articular cartilage that covers the ends of the thigh and shin bones. While initially relieving pain and restoring mobility, this can accelerate deterioration of the knee joint and frequently leads to the patient developing OA.
Orthox has developed and plans to bring to market FibroFixTM – an innovative implant developed to treat debilitating knee cartilage injuries including damage to the articular cartilage in the knee, degeneration and OA.
The objective of the project has been to clinically validate FibroFixTM through pivotal clinical trials, build manufacturing capability, and create the platform for post-project commercialisation of the innovation.
Keyhole surgery to treat knee injury is the most common orthopaedic procedure. The majority involve removing damaged cartilage from either the shock absorbing meniscus or from the smooth, stiff articular cartilage that covers the ends of the thigh and shin bones. While initially relieving pain and restoring mobility, this can accelerate deterioration of the knee joint and frequently leads to the patient developing OA.
Orthox has developed and plans to bring to market FibroFixTM – an innovative implant developed to treat debilitating knee cartilage injuries including damage to the articular cartilage in the knee, degeneration and OA.
The objective of the project has been to clinically validate FibroFixTM through pivotal clinical trials, build manufacturing capability, and create the platform for post-project commercialisation of the innovation.
During the first reporting period, Orthox completed the preclinical verification, validation testing of FibroFix™ Cartilage and the associated surgical instrument set, and prepared the majority of documentation required for clinical trial submissions. The preclinical results showed the FibroFix™ implants to be completely biocompatibility under the rigorous ISO10993 requirements; show promising performance in an appropriate animal model of cartilage repair demonstrating implant integration and new cartilage deposition; possess excellent physical properties including mechanical and surface properties that were a close match for human cartilage tissue; and could be implanted using a quick, straightforward and reproducible surgical procedure that resulted in stable implant fixation into the knee joint. The company also made considerable progress on the production scale up, validation and regulatory certification achieving compliance with ISO13485 manufacturing standard and GMP production.
During the second period of the project manufacturing scale up to meet clinical trial requirements was successfully completed, a new company website was launched and, with the removal of Covid-19 restrictions, project results were disseminated more widely through conference presentations as well as project press releases and video productions. A new Company business plan and associated investor materials were developed and used to successfully raise Series A investment finance which was used to support project objectives including progress of FibroFix™ Cartilage into clinical phase (The FFLEX Study).
Clinical trial submissions for the FFLEX clinical study to evaluate FibroFix™ Cartilage in 75 patients were made to the national ethical and regulatory authorities in the UK. The FFLEX clinical investigation (ClinicalTrials.gov Identifier: NCT05560490) pre-market clinical investigation was a multicentre, prospective, non-randomised, open-label, first-in-human clinical investigation using FibroFix™ Cartilage to treat large (up to 5cm2) and potentially osteoarthritic lesions in the smooth, stiff articular cartilage found in joints. The objective of this clinical investigation was to demonstrate the clinical safety and performance of FibroFix™ Cartilage.
In a change to the projects structure, to mitigate the risks presented by the combination of Brexit and the Covid-19 pandemic, clinical trial submissions were also brought forward in continental Europe as well, with an application to run the FFLEX clinical trial in Hungarian sites made to the national ethical and regulatory authorities there too. Approvals from all requisite authorities in both countries were achieved and recruitment of the FFLEX clinical trial was initiated with two patients enrolled onto the Study in late 2022.
FibroFix™ Cartilage P was implanted into 2 patients at the lead site the UK site, Bristol Southmead Hospital, for repair of major cartilage lesions in the medial femoral condyle of the knee joint. Initial clinical signs were positive with encouraging patient recovery and initial pain reduction. Implants were retained in the implantation site with no indication of structural deterioration on MRI. However, persistent swelling in the implanted joints led to implant removal between 3 and 6 months and the trial being halted with root cause analysis undertaken.
During the second period of the project manufacturing scale up to meet clinical trial requirements was successfully completed, a new company website was launched and, with the removal of Covid-19 restrictions, project results were disseminated more widely through conference presentations as well as project press releases and video productions. A new Company business plan and associated investor materials were developed and used to successfully raise Series A investment finance which was used to support project objectives including progress of FibroFix™ Cartilage into clinical phase (The FFLEX Study).
Clinical trial submissions for the FFLEX clinical study to evaluate FibroFix™ Cartilage in 75 patients were made to the national ethical and regulatory authorities in the UK. The FFLEX clinical investigation (ClinicalTrials.gov Identifier: NCT05560490) pre-market clinical investigation was a multicentre, prospective, non-randomised, open-label, first-in-human clinical investigation using FibroFix™ Cartilage to treat large (up to 5cm2) and potentially osteoarthritic lesions in the smooth, stiff articular cartilage found in joints. The objective of this clinical investigation was to demonstrate the clinical safety and performance of FibroFix™ Cartilage.
In a change to the projects structure, to mitigate the risks presented by the combination of Brexit and the Covid-19 pandemic, clinical trial submissions were also brought forward in continental Europe as well, with an application to run the FFLEX clinical trial in Hungarian sites made to the national ethical and regulatory authorities there too. Approvals from all requisite authorities in both countries were achieved and recruitment of the FFLEX clinical trial was initiated with two patients enrolled onto the Study in late 2022.
FibroFix™ Cartilage P was implanted into 2 patients at the lead site the UK site, Bristol Southmead Hospital, for repair of major cartilage lesions in the medial femoral condyle of the knee joint. Initial clinical signs were positive with encouraging patient recovery and initial pain reduction. Implants were retained in the implantation site with no indication of structural deterioration on MRI. However, persistent swelling in the implanted joints led to implant removal between 3 and 6 months and the trial being halted with root cause analysis undertaken.
To prevent total knee replacement, many patients who suffer injury to the meniscus or knee cartilage are advised to limit their activity or risk deterioration of the joint. Orthox offers an alternative: strong, resilient, natural implants capable of restoring knee function while allowing the body’s own cells to grow through, and integrate with, the device.
FibroFixTM technology has the capacity to functionally replace articular and meniscal cartilage, while supporting tissue regeneration. This is achieved without needing expensive cells or biologics. It is expected that this solution will allow patients to swiftly return to a fully active, pain-free lifestyle.
The setback in the clinical trial on the project is under investigation and depending on the result of these analyses, remedies are expected to be implemented to address the challenges presented provided further funding can be sourced to support these efforts. Irremediable problems are considered unlikely owing to the long history of biocompatibility of the fundamental material employed in the implants, silk fibroin, and the preclinical evidence supporting this generated on the project.
FibroFixTM technology has the capacity to functionally replace articular and meniscal cartilage, while supporting tissue regeneration. This is achieved without needing expensive cells or biologics. It is expected that this solution will allow patients to swiftly return to a fully active, pain-free lifestyle.
The setback in the clinical trial on the project is under investigation and depending on the result of these analyses, remedies are expected to be implemented to address the challenges presented provided further funding can be sourced to support these efforts. Irremediable problems are considered unlikely owing to the long history of biocompatibility of the fundamental material employed in the implants, silk fibroin, and the preclinical evidence supporting this generated on the project.