Periodic Reporting for period 3 - OSTEOproSPINE (Novel Bone Regeneration Drug Osteogrow: Therapeutic Solution for Lumbar Back Pain)
Período documentado: 2021-01-01 hasta 2022-06-30
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, in particular in patients with degenerative spine disorder is around 1.5 million, 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 that would extend the currently available treatment options are urgently needed.
The research performed within the project is based on a therapeutic system developed in the course of the former 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 project 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, the five-year project 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.
The research performed within the project is based on a therapeutic system developed in the course of the former 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 project 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, the five-year project 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.
The consortium partners are working together to conduct a Phase II, randomized, patient- and evaluator-blinded clinical trial of OSTEOproSPINE in Austria. At the start of the project the clinical trial received the necessary ethics and regulatory approvals, and after the supply of the investigational medicinal product (IMP) was ensured and data management tools (eCRF) and procedures established, the study was initiated at the Vienna clinical site with First Patient First Visit in May 2018. Stage 1 of the trial including enrolment and treatment of 15 patients was finalized in September 2018 and following 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 IDSMB positive evaluation of available 3-month follow-up data from 45 patients. The coronavirus pandemic emergency measures in Austria instigated Urgent safety measures to be implemented in April 2020 at the time when trial was not actively recruiting due to interim data analysis according to the study protocol. Stage 3 of the trial was initiated in June 2020 and patient recruitment was concluded in June 2021. Although pandemic rules interrupted the usual hospital and some trial procedures, overall the trial is proceeding without major obstacles finalizing patient follow-up visits and data collection.
In parallel with the clinical study, further development of the product is being conducted with the aim to optimize the manufacturing process and upgrade the infrastructure. Additionally, the new OSTEOproSPINE formulation has been designed and tested in additional preclinical studies boosting its differentiation and market potential.
The consortium maintains regular and intensive communication on all aspects of ongoing and future activities through regular team teleconferences, e-mail exchanges, telephone calls and face-to-face meetings (one-on-one, focused groups, site initiation, monitoring, audit, and general assembly). Established management structure and support mechanisms enable a smooth project workflow and ensure that all contractual commitments are met in time, including the ethics requirements. Project partners published 15 scientific papers since the beginning of the project and are engaged in dissemination and communication of project information to various stakeholders.
In parallel with the clinical study, further development of the product is being conducted with the aim to optimize the manufacturing process and upgrade the infrastructure. Additionally, the new OSTEOproSPINE formulation has been designed and tested in additional preclinical studies boosting its differentiation and market potential.
The consortium maintains regular and intensive communication on all aspects of ongoing and future activities through regular team teleconferences, e-mail exchanges, telephone calls and face-to-face meetings (one-on-one, focused groups, site initiation, monitoring, audit, and general assembly). Established management structure and support mechanisms enable a smooth project workflow and ensure that all contractual commitments are met in time, including the ethics requirements. Project partners published 15 scientific papers since the beginning of the project and are engaged in dissemination and communication of project information to various stakeholders.
The results generated within OSTEOproSPINE project are enabling the creation of innovative new medicinal product portfolio (OSTEGROW family of products) that is already finding its usefulness in various medical indication. Surgeons treating patients with bone fracture non-unions, degenerative disc disorders (DSDs) and with periodontal disease on teeth will have the access to the new therapeutic options through planned clinical trials offering patients favourable outcomes for their debilitating conditions. Due to their biological attributes, OSTEOGROW products will be able to form sufficient quantities of new bone, enabling better surgery outcomes and improve patient quality of life. Positive results from the proposed study may ultimately have a profound effect on the financial burden to society.
The results of the ongoing regenerative medicine clinical trial are already suggesting that the new therapy has the necessary prerequisites to safely reach the next level of clinical testing and be used in medical practice. This could also further stimulate 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.
The results of the ongoing regenerative medicine clinical trial are already suggesting that the new therapy has the necessary prerequisites to safely reach the next level of clinical testing and be used in medical practice. This could also further stimulate 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.