The study analyzes the compressive properties of engineered cartilage tissue grown with chondrocytes seeded in a porous scaffold based on work completed as part of a sponsored research agreement between Histogenics and Dr. Lawrence Bonassar of Cornell University.
The initial data were presented at the Orthopaedic Research Society annual meeting in March 2017. The lead author is Jill E. Middendorf of Cornell with support from Lena Bartell; Itai Cohen, Ph.D. and Lawrence J. Bonassar, Ph.D. of Cornell; and Sonya Shortkroff, Caroline Dugopolski, Stephen Kennedy and Joseph Siemiatkoski of Histogenics.
The goal of the study was to understand how the deposition of glycosaminoglycans (GAG), a component of the extracellular matrix (ECM), influences the microscale compressive properties of tissue engineered cartilage that was produced using a lab-scale process designed to mimic that of NeoCart. The compressive properties were specifically analyzed by looking at localized scaffold buckling. Histogenics intends to use the results of this study to provide additional data to the U.S. Food and Drug Administration (FDA) as part of a potential Biologics License Application (BLA) for NeoCart, subject to a successful outcome in the ongoing Phase 3 clinical trial of NeoCart.
“Our collaboration with Cornell continues to generate valuable data that further characterizes our unique mechanism of action which we intend to use to support a potential BLA filing for NeoCart. In addition, these data will be critical for future development of other candidates in the NeoCart product platform,” said Stephen Kennedy, chief technology officer of Histogenics. “These data add to the strong body of evidence demonstrating that our combination of cells, scaffold and tissue engineering which produces cartilage tissue ex-vivo are critical for these therapies to function properly upon implantation in the body. We believe that NeoCart is unique in exhibiting these characteristics prior to implantation and are confident that this is one of the reasons we have seen such early preliminary recovery from pain and return to function as demonstrated by the data from the Phase 1 and 2 clinical trials of NeoCart.”
The compressive properties of the tissue implants improve with increased processing time, as ECM is deposited in the scaffold pores and are highly correlated to the GAG content of the constructs. Scaffolds seeded with chondrocyte cells absent significant extracellular matrix and GAG deposition have a strong tendency to buckle or collapse, resulting in sub-optimal biomechanical properties of such cartilage tissue implants. The reported results are consistent with earlier work demonstrating that in-vitro cartilage constructs, or tissue implants, produced using a process that is designed to mimic that of NeoCart exhibit mechanical properties prior to implantation approaching such properties of native cartilage. Together, these attributes may enable the early response and repair of focal cartilage lesions and these findings are consistent with data seen in patients in the Phase 1 and 2 clinical trials of NeoCart.
“Developing cartilage tissue implants with appropriate mechanical properties has been a challenge for many years. It is clear that deposition of ECM improves mechanical performance, but the mechanism behind this improvement has not been clear,” stated Bonassar, a professor at Cornell in the Meinig School of Biomedical Engineering and the Sibley School of Mechanical and Aerospace Engineering. “These data demonstrate newly synthesized ECM reinforces the structure of porous scaffolds and greatly enhances biomechanical competence of engineered cartilage tissue.”
NeoCart is a cartilage-like, tissue engineered implant created from a patient’s own cartilage cells. NeoCart is designed to exhibit characteristics of articular, hyaline cartilage prior to and upon implantation into the knee and therefore does not rely on the body to make new cartilage. The patient’s cells are multiplied in Histogenics’ laboratory and then infused into a proprietary scaffold to allow them to organize and function like cartilage cells. Before NeoCart is shipped to the surgeon for implantation, the cell and scaffold construct undergoes a bioengineering process that is designed to mimic a joint so that the implant, upon placement in the knee with a proprietary bioadhesive, is primed to begin functioning like healthy cartilage. As a result, NeoCart is the only product in development or on the market with a one-year primary superiority endpoint as compared to the standard of care. NeoCart is currently in a Phase 3 clinical trial that is designed to evaluate the safety and efficacy of NeoCart as a first-line therapy for full thickness knee cartilage defects in skeletally mature adults ages 18 to 59 and to show superiority of NeoCart at one year post implantation against the current standard of care, microfracture. Histogenics completed enrollment in the Phase 3 clinical trial in the second quarter of 2017, is conducting the trial under a SPA with the FDA and expects to report topline data in the third quarter of 2018. NeoCart is not approved for sale in any jurisdiction.
Histogenics is a cell therapy company developing and commercializing novel tissue therapies that may offer more rapid and durable recoveries for patients with pain and loss of function due to musculoskeletal conditions. Waltham, Mass.-based Histogenics’ regenerative medicine platform combines expertise in cell processing, scaffolding, tissue engineering and bioadhesives to create tissue ex-vivo. Histogenics’ first investigational product candidate, NeoCart is designed to treat cartilage defects in the knee. There are more than 500,000 or more knee cartilage procedures in the United States each year, with many healthy active adults avoiding treatment as they seek other alternatives. Left untreated, even a small cartilage defect can expand in size and progress to debilitating osteoarthritis, ultimately necessitating a joint replacement procedure. Osteoarthritis is more common in adults over the age of 50, but the condition and precursors of the condition can be observed much earlier, and cartilage damage is believed to be one of the leading contributors of this disease.