Available online 10 September 2022, 150956

The NeoCart® implant (Histogenics Corporation, Waltham, MA) is a cell-based therapeutic for the restoration of articular cartilage defects. The implant is composed of a type I collagen scaffold, inoculated with expanded autologous chondrocytes, and preconditioned under hydrostatic loading and low oxygen tension. The process was designed to create an autogenous chondrogenic construct for application during a surgical biologic reconstruction procedure for patients with symptomatic cartilage disease. Favorable pre-clinical basic science and animal studies characterizing the regenerative potential of NeoCart led to application for United States Food and Drug Administration (FDA) approval as the first autologous tissue therapeutic for articular cartilage restoration, beginning with a Phase I safety trial in 2003.

Deemed safe in Phase I and efficacious in Phase II relative to “standard of care” microfracture, a Phase III randomized controlled superiority trial versus microfracture was authorized by FDA in 2010. The primary outcome measure of a statistically significant difference in the number of responders to treatment versus control cohorts based on meeting a dual-criteria threshold of >20-point and >12-point improvement in International Knee Documentation Committee (IKDC) and Knee Injury and Osteoarthritis Outcome Score (KOOS) pain domain scores, respectively, was established. The 1-year protocol assessment metric for superiority was narrowly missed, which led to termination of the trial in 2019. Ultimately, the therapy was not approved for use by the FDA. The history of this case example: quelching a biologically safe and effective therapeutic, highlights hurdles in the complex process of bringing scientifically sound products to patients through regulatory processes in the United States.

NeoCart

microfracture

autologous chondrocyte implantation

randomized clinical trial

FDA

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