GENE THERAPY PRODUCTS

After more than two decades of the first gene therapy trial in human [90,91], the first commercial gene therapy product, Gendicine, manufactured by SiBiono was approved in 2003 by China’s State Food and Drug Administration for the treatment of head and neck squamous cell carcinoma [129—132]. The product utilizes recombinant adenovirus as vector to deliver wild-type p53 gene, the expression of which is known to transfer antitumor abilities into the nucleus of tumor cells [116,117]. A Biologics License Application (BLA) for a similar (to Gendicine) therapy, Advexin [133], an orphan-designated therapy by Introgen for the treatment of head and neck cancer as well as Li-Fraumeni syndrome, was turned down by the US FDA in September 2008.

In 2007 another gene therapy product, Rexin-G, which was the first targeted injectable gene therapy product, was approved by regulatory authorities in the Philippines for the treatment of all solid tumors [134]. Rexin-G employs a retroviral-based vector to deliver “a gene for a dominant-negative mutant form of human cyclin G1 which stops cell cycle by blocking endogenous cyclin-G1 protein” [79].

In November 2012, another gene therapy product by UniQure, Glybera (alipogene tiparvovec), was approved by the European Medicines Agency for the treatment of lipoprotein lipase (LPL) deficiency [135]. This marks the first gene therapy product to be granted a BLA in Europe. The product employs adenoassociated virus as a vector to convey a functional replica of the LPL gene to skeletal muscle [135]. UniQure’s application for Glybera approval in the United States was turned down by the FDA as the regulatory body suggested further clinical trials [136,137]. UniQure plans to carry out additional clinical trials for Glybera in early 2016, to be incorporated in a BLA submission to the FDA.