Periodic Reporting for period 4 - OSTEOproSPINE (Novel Bone Regeneration Drug Osteogrow: Therapeutic Solution for Lumbar Back Pain)
Reporting period: 2022-07-01 to 2023-06-30
Chronic lumbar back pain, caused most often by degenerative spine disorders (DSD), affects millions of people worldwide and impairs the patient’s physical, psychological and social functioning. The prevalence of lumbar back pain requiring surgical intervention in EU represents a high burden for health care insurance agencies ranging in millions of Euros. Due to its high incidence (lumbar back pain is the second most common medical condition after common cold) and chronic nature, lumbar back pain is a frequent cause of absenteeism and thus has a direct impact on the economy. After therapeutic options to control the pain are exhausted, the patients need to undergo a spinal fusion, a surgical procedure that corrects spinal instability and alleviates lumbar back pain with associated leg pain. Unfortunately, the success rate of spinal fusion surgery is modest (approximately 35%). Novel therapies to extend the available treatment options are urgently needed.
The research performed within the project is based on a therapeutic system developed in the course of the FP7 project OSTEOGROW in which an autologous carrier and a biologically active protein (recombinant human bone morphogenetic protein 6 [rhBMP6]) are combined into an implant which accelerates and enhances bone repair. In OSTEOproSPINE, the implant is reinforced with a compression-resistant matrix to guide the formation of new bone at the extraskeletal site and replace bone harvested from the patient’s iliac crest for the fusion of lumbar vertebrae. By generating new bone, OSTEOproSPINE will restore the spine’s weight-bearing function, reduce the severity of back pain and improve the success rate of posterolateral spinal fusion surgery. The overall goal of OSTEOproSPINE is to provide a long-term solution for the treatment of degenerative spine disorder through a personalised bone implant.
To allow better treatment of degenerative spine disorder, OSTEOproSPINE pursues the following specific objectives:
• to evaluate the safety and efficacy of the OSTEOproSPINE regenerative treatment for spinal fusion and relief of lumbar back pain in a phase II clinical trial;
• to achieve long-lasting pain relief for patients with degenerative disc diseases;
• to evaluate whether the new bone regeneration drug Osteogrow together with allograft bone as a compression-resistant matrix (OSTEOproSPINE) can replace autologous iliac crest bone graft in patients undergoing PLIF and omit a second surgical procedure for harvesting pelvic bone;
• to obtain first clinical evidence of efficacy and safety of two OSTEOGROW doses for PLIF, in comparison with autologous bone grafting;
• to develop the basis for a series of products able to form extra-skeletal bone by tissue engineering.
During the 66 months of project implementation all the set-up objectives have been achieved. The clinical trial was successfully conducted and finalized for the included patients, despite difficult pandemic conditions. The clinical results indicate efficacy and safety of the therapy compared to the standard of care suggesting that an alternative treatment to autologous bone grafting is now available. The OSTEOGROW family of products have been developed and are being tested in additional indications, expanding the clinical use of this new regenerative therapy.
The research performed within the project is based on a therapeutic system developed in the course of the FP7 project OSTEOGROW in which an autologous carrier and a biologically active protein (recombinant human bone morphogenetic protein 6 [rhBMP6]) are combined into an implant which accelerates and enhances bone repair. In OSTEOproSPINE, the implant is reinforced with a compression-resistant matrix to guide the formation of new bone at the extraskeletal site and replace bone harvested from the patient’s iliac crest for the fusion of lumbar vertebrae. By generating new bone, OSTEOproSPINE will restore the spine’s weight-bearing function, reduce the severity of back pain and improve the success rate of posterolateral spinal fusion surgery. The overall goal of OSTEOproSPINE is to provide a long-term solution for the treatment of degenerative spine disorder through a personalised bone implant.
To allow better treatment of degenerative spine disorder, OSTEOproSPINE pursues the following specific objectives:
• to evaluate the safety and efficacy of the OSTEOproSPINE regenerative treatment for spinal fusion and relief of lumbar back pain in a phase II clinical trial;
• to achieve long-lasting pain relief for patients with degenerative disc diseases;
• to evaluate whether the new bone regeneration drug Osteogrow together with allograft bone as a compression-resistant matrix (OSTEOproSPINE) can replace autologous iliac crest bone graft in patients undergoing PLIF and omit a second surgical procedure for harvesting pelvic bone;
• to obtain first clinical evidence of efficacy and safety of two OSTEOGROW doses for PLIF, in comparison with autologous bone grafting;
• to develop the basis for a series of products able to form extra-skeletal bone by tissue engineering.
During the 66 months of project implementation all the set-up objectives have been achieved. The clinical trial was successfully conducted and finalized for the included patients, despite difficult pandemic conditions. The clinical results indicate efficacy and safety of the therapy compared to the standard of care suggesting that an alternative treatment to autologous bone grafting is now available. The OSTEOGROW family of products have been developed and are being tested in additional indications, expanding the clinical use of this new regenerative therapy.
The consortium partners successfully completed the Phase II, randomized, patient- and evaluator-blinded clinical trial of OSTEOproSPINE. The clinical trial received the necessary ethics and regulatory approvals, and was initiated at the Vienna clinical site in May 2018. Stage 1 of the trial including enrolment and treatment of 15 patients was finalized in September 2018.After a 3 months follow-up, the Independent Data Safety Monitoring Board (IDSMB) concluded that safety data supported the continuation of the trial. Stage 2 of the trial started in February 2019 after the initiation of two additional clinical sites (Linz and Graz) and was concluded in May 2020 by a positive IDMSB evaluation of available 3-month follow-up data from 45 patients. The COVID-19 emergency measures in Austria instigated urgent safety measures to be implemented in April 2020. Stage 3 of the trial was initiated in June 2020 and patient recruitment was concluded in June 2021. Certain adjustments were needed during implementation due to initial slow recruitment rates as well as strict pandemic rules at clinical sites. However, the trial has been conducted without major obstacles, patient follow-up visits were finalized by March 2023 enabling the collection of the data necessary for statistical analyses. The results of the trial indicate non-inferiority of the tested therapy compared to standard of care in terms of radiographic fusion, improvement of spinal function and back pain relief and superiority in leg pain relief and physical health status. Additionally, the benefits of the therapy were also demonstrated in terms of safety parameters (significantly lower incidence of severe adverse events).
In parallel to the clinical study, further development of product manufacturing is being conducted to ensure the optimal protein production process including the upgrade of the existing infrastructure. Additionally, the new formulations have been designed and tested in preclinical studies boosting their differentiation and market value. New products are already being evaluated in ongoing clinical trials for different indications expanding their therapeutic potential and clinical use.
The consortium maintained regular and intensive communication on all aspects of ongoing and future activities. Established management structures and support mechanisms enabled a smooth project workflow and ensured that all contractual commitments were met in time. Team members published 17 scientific papers and are engaged in intensive dissemination and communication of project information to various stakeholders. The intensive innovation exploitation activities include technology transfers to strategic pharma partners, IP management and IP protection, preclinical and clinical development of new formulations as well as applications for additional funding.
In parallel to the clinical study, further development of product manufacturing is being conducted to ensure the optimal protein production process including the upgrade of the existing infrastructure. Additionally, the new formulations have been designed and tested in preclinical studies boosting their differentiation and market value. New products are already being evaluated in ongoing clinical trials for different indications expanding their therapeutic potential and clinical use.
The consortium maintained regular and intensive communication on all aspects of ongoing and future activities. Established management structures and support mechanisms enabled a smooth project workflow and ensured that all contractual commitments were met in time. Team members published 17 scientific papers and are engaged in intensive dissemination and communication of project information to various stakeholders. The intensive innovation exploitation activities include technology transfers to strategic pharma partners, IP management and IP protection, preclinical and clinical development of new formulations as well as applications for additional funding.
The results generated within OSTEOproSPINE enable the creation of aninnovative new medicinal product portfolio (OSTEGROW family of products) that is already finding its usefulness in various medical indications. Surgeons treating patients with bone fracture non-unions, DSDs and with periodontal disease on teeth are already having access to the new therapeutic options through initiated clinical trials offering patients favourable outcomes for their debilitating conditions. Due to their biological attributes, OSTEOGROW products are able to form sufficient quantities of new bone, enabling better surgery outcomes and improve patient quality of life.
The results of the completed regenerative medicine clinical trial are indicating that the new therapy has the necessary prerequisites to be progressed to higher stages of clinical testing and, if successful, be used in medical practice. This is already a stimulating growth and competitiveness of European small and medium-sized enterprises and increase the attractiveness of and investment in Europe as a location of choice for the development of new therapeutic options in regenerative medicine. Positive results from the finalized study may ultimately have a profound effect on the financial burden to the society.
The results of the completed regenerative medicine clinical trial are indicating that the new therapy has the necessary prerequisites to be progressed to higher stages of clinical testing and, if successful, be used in medical practice. This is already a stimulating growth and competitiveness of European small and medium-sized enterprises and increase the attractiveness of and investment in Europe as a location of choice for the development of new therapeutic options in regenerative medicine. Positive results from the finalized study may ultimately have a profound effect on the financial burden to the society.