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integration_of_nvd-001_in_intervertebral_body_cage_fusion

Bone regeneration stem cell “putty” sees positive results in trials

pharmafile | June 15, 2021 | News story | Manufacturing and Production | Cell regeneration, Stem cells, bone, platform, technology

Belgian clinical stage company, Novadip Biosciences, has announced positive results from its Phase I trial of its autologous cell-based osteogenic (bone healing) product, NVD-001, in patients needing single-level spinal fusion.

NDV-001 is a clinical-stage investigational cell-based therapy, which represents a new paradigm in regenerative medicine. It is an autologous cellular medicinal product obtained by the culture of adipose tissue, which leads to osteogenic cells after ex vivo isolation, expansion, and differentiation of pluripotent adipose-tissue stem cells. This is combined with an allogeneic fully demineralised bone matrix into a 3D bone implant, which upon implantation the bone-forming cells continue to mature and progressively transform the putty into normal, healthy bone.

NVD-001 was created using Novadip’s tissue regeneration technology platform, 3M³, and the Phase I trial evaluated NVD-001 safety and preliminary effectiveness for the treatment of low grade degenerative lumbar spondylolisthesis by interbody fusion of one vertebral segment.

The study included 32 patients in total, of whom 23 were NVD-001 patients with the remaining nine being standard of care patients from centres in Belgium, Poland, and the Czech Republic.

The key findings from the trial were as follows:

The primary endpoint of safety was met. NVD-001 demonstrated a favourable safety profile over a two-year observation period.
NVD-001 did not require additional surgical time without autologous bone harvesting and did not prolong the time spent in hospital.
NVD-001 demonstrated beneficial effects on the quality of life of patients with reduction of pain and increase of walking capacity.
NVD-001 demonstrated proof of concept of osteogenesis and osteoinduction in the intervertebral body space, which is known to be a challenging environment for bone formation.

Image: NVD-001 Product

Gunnar Anderson, Professor and Chairman Emeritus of the Department of Orthopaedic Surgery at Rush University Medical Center, and Chairman of the Scientific Advisory Board of Novadip, said: “The results of this study clearly demonstrate the safety of Novadip’s 3-dimensional autologous adipose-derived bone product.

“The study was not powered to show differences between groups but is hugely encouraging with excellent bone formation. Based on this data, the development candidate, NVD-003, has the potential to become the solution for both patients undergoing spinal fusion and those with large bone defects where there is currently an unmet need.”

Following the success of NVD-001, Novadip has announced a shift in focus towards its next-generation programme, NVD-003. NVD-003 was granted Orphan Drug designation and Rare Paediatric Disease designation by the FDA this year for congenital pseudarthrosis of the tibia, a rare debilitating condition which mainly affects children.

For the physician, NVD-003 is in the form of a mouldable putty in quantities large enough to fill small as well as large bone defects (>20cm³) using classical or minimally invasive surgery techniques. It is formulated by extracting stem cells from the patient from only a few millilitres of fatty tissue which are then cultured in vitro to become a biomaterial consisting of bone forming cells embedded in their self-secreted extracellular matrix together with added hydroxyapatite particles. NVD-003 is therefore more mineralised than NVD-001, which enables a faster bone formation.

Dr Denis Dufrane, Chief Executive Officer and founder of Novadip, said: “As we progress our development candidate, NVD-003, we are encouraged by these results which validate our proprietary cell therapy 3M³ platform. By mimicking the process of natural healing, our 3M³ platform technology can deliver extraordinary outcomes for patients. We are excited to further progressing NVD-003 with interim efficacy data in bone non-union expected later this year.”

Kat Jenkins