JX-594 is an oncolytic virus (also known as Pexa-Vec, INN pexastimogene devacirepvec) developed by Jennerex and partners: Transgene S.A.; Lee's Pharmaceutical Holdings Ltd.; and Green Cross Corp. Pexa-Vec is designed to target and destroy cancer cells.
JX-594 is a modified Copenhagen strain (or Wyeth strain) vaccinia poxvirus engineered by addition of the GM-CSF gene and deletion of the thymidine kinase gene which limits viral replication to cells with high levels of thymidine kinase, typically seen in cancer cells with a mutated RAS or p53 gene. The virus also has the LacZ gene insertion under control of the p7.5 promoter. The virus kills the infected/cancer cells by lysis and also expresses GM-CSF which may help initiate an anti-tumour immune response.
It has orphan drug designation from US FDA and EUMA for the treatment of hepatocellular carcinoma (HCC).
In clinical trials doses have been administered by intratumoral or intravenous injection.
Clinical trials
A global Phase 3 trial (the PHOCUS trial) http://www.pexavectrials.com for patients with advanced stage hepatocellular carcinoma will begin enrolling patients in late 2015. Two Phase I trials have reported results and a phase II trial for primary liver cancer, alone and in combination with sorafenib have been completed.
JX-594 Phase I results in 23 patients had encouraging results in 6 of 8 high dosed patients. A small (30 patient) phase II trial in advanced hepatocellular carcinoma (HCC) showed an increased median overall survival of 13.8 months compared 6.7 months for a lower dose (p=0.029).