Jennerex publishes proof-of-concept data for oncolytic virus therapy
This article was originally published in Scrip
As privately-owned Jennerex published positive results from a proof-of-concept study evaluating its oncolytic therapy, JX-594 (also TG6006), in patients with metastatic melanoma, the company reiterated previously announced plans to begin a Phase IIb trial of the product in advanced liver cancer in Q3 of year.
The product is an engineered oncolytic virus designed to selectively target and destroy cancer cells through three mechanisms of action. First is the lysis of cancer cells through viral replication, second is the reduction of the blood supply to tumours by vascular targeting and destruction, finally stimulation of the body's immune response against cancer cells.
The published data appears in the peer-reviewed journal, Molecular Therapy, and comes from a mechanistic proof-of-concept study that enrolled 10 treatment-refractory Stage IV melanoma patients, eight of whom completed the study. They all received up to nine weekly intratumoural injections of the product at a low dose (less than 10 percent of the dose given in other JX-594 trials) and evidence of activity was assessed in blood samples and tumour biopsies.
Blood samples collected over the course of treatment demonstrated JX-594 replication after repeated dosing as well as the expression and functionality of JX-594 encoded transgenes. Tumour biopsies showed tumour cell necrosis (death) and immune cell recruitment into tumours. The drug was safe and well-tolerated, with flu-like symptoms as the most common side effect for patients.
The San Francisco-based company noted, "JX-594 replication was observed following multiple rounds of intratumoural JX-594 therapy, providing proof-of-concept data for the potential benefit of chronic administration regimens of the product."
It added that the trial in metastatic melanoma provides additional key information for its JX-594 programme and complements the ongoing clinical development of the product, which is expected to enter a randomised Phase IIb trial in advanced liver cancer later this year.
Jennerex has a number of licensing deals for the product and France’s Transgene holds an exclusive license to develop and commercialise JX-594 in Europe and neighbouring countries. In its R&D day last month, Transgene said the Phase IIb hepatocarcinoma study would start in the next few months (scripintelligence.com, 7 June 2011).
A Transgene spokesperson explained the significance of the published data to Scrip: “The concept of [the] oncolytic virus and oncolytic virotherapy (such as JX594) is tumour tissue selective replication and thus selective tumour cell lysis / destruction. Therefore the demonstration and evaluation of virus replication in the melanoma cancer tissues of these patients is critical and in fact does support the mechanism of action of JX594. Furthermore upon intratumoral injection they have also observed the presence of the virus in non-injected tumour biopsies: this is only possible if the virus infected the tumour where it was injected, then subsequently spread to distant sites of the disease, then subsequent productive (replication) infection at the non- injected site.”
She added: "Through the above described mechanisms of action, virtually all or most solid tumours [at the] metastatic stage can be a target for JX594. Tumour-selective replication and oncolysis is not restricted to certain tumour types."
Phase I and Phase II trials in multiple cancer types to date have shown that JX-594, delivered either directly into tumours or systemically, induces tumour shrinkage and/or necrosis and the product was well-tolerated in more than 100 patients who have been treated to date, Jennerex noted. Objective tumour responses have been demonstrated in a number of cancers including liver, colon, kidney, lung and melanoma.
The Transgene spokesperson noted that liver cancer is the current lead indication for the drug, with the Phase IIb TRAVERSE study in hepatocellular carcinoma patients who have failed sorafenib treatment, expected to start in Q3 of 2011. A Phase III frontline study in hepatocellular carcinoma will follow the Phase IIb trial with a potential filing slated for the end of 2015. The second indication being pursued is third-line use in metastatic colorectal cancer, for which a Phase I/II trial will start in Q4 2011.
In other territories, Green Cross Corporation holds an exclusive license to develop and commercialise JX-594 in South Korea, and Lee's Pharmaceutical holds the same in China.