Pexastimogene devacirepvec

JX-594 is an oncolytic virus (also known as Pexa-Vec,[1] INN pexastimogene devacirepvec[2]) 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.[3]

JX-594 is a modified Copenhagen[4] strain (or Wyeth strain[2]) 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.[5] The virus also has the LacZ gene insertion under control of the p7.5 promoter.[2] The virus kills the infected/cancer cells by lysis and also expresses GM-CSF which may help initiate an anti-tumour immune response.[6][7] [8]

It has orphan drug designation from US FDA and EUMA for the treatment of hepatocellular carcinoma (HCC).[1]

In clinical trials doses have been administered by intratumoral or intravenous injection.[2]

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.[7]

JX-594[9] Phase I results in 23 patients had encouraging results in 6 of 8 high dosed patients.[10] 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).[11]

References

  1. 1 2 Jennerex Granted FDA Orphan Drug Designation for Pexa-Vec in Hepatocellular Carcinoma (HCC)
  2. 1 2 3 4 Phase 1 Study of Intratumoral Pexa-Vec (JX-594), an Oncolytic and Immunotherapeutic Vaccinia Virus, in Pediatric Cancer Patients
  3. ↑ Un virus contre le cancer 25 March 2012, Radio Canada (French)
  4. ↑ Transgene Presents Data on Improved Cytotoxic Activity of Oncolytic Viruses Expressing Intrabodies in Resistant Tumor Cell Lines. Oct 2016
  5. ↑ Bos, JL (Sep 1, 1989). "ras oncogenes in human cancer: a review.". Cancer Research. 49 (17): 4682–9. PMID 2547513.
  6. ↑ "NCI Drug Dictionary". National Cancer Institute. Retrieved 25 March 2013.
  7. 1 2 "Novel Cancer-Targeting Virus Therapy Shows Efficacy in Early-Stage Trial". 31 August 2011.
  8. ↑ Breitbach at al. (2011). "Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans". 477 (7362): 99–102. doi:10.1038/nature10358. PMID 21886163.
  9. ↑ http://www.voanews.com/english/news/health/Cancer-Fighting-Engineered-Virus-Makes-Medical-History-128899673.html September 01, 2011 Voice of America
  10. ↑ "Cancer-fighting virus shown to target tumors alone". Aug 31, 2011.
  11. ↑ "AASLD: Virus Shuts Down Liver Cancer in Early Trials". Nov 2011.

External links

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