Preliminary data from a randomized dose-ranging Phase II trial of JX-594, which is being developed by Jennerex, Transgene (a member of the Institut Merieux Group), Green Cross Corporation, in patients with advanced liver cancer is showing a benefit in overall survival for the high dose group.
The preliminary data from the study HEP007 indicated that the risk of death for patients who received JX-594 at the high therapeutic dose was markedly reduced by more than 50% (hazard ratio < 0.5) when compared to patients randomized to a control low dose (one-tenth of the high dose).
Proprietary, engineered oncolytic virus
JX-594 is a proprietary, engineered oncolytic virus that is designed to selectively target and destroy cancer cells through three diverse mechanisms of action including the lysis of cancer cells through viral replication, the reduction of the blood supply to tumors through vascular targeting and destruction, and the stimulation of the body’s immune response against cancer cells, (i.e., active immunotherapy).
To date, Phase I and II trials in multiple cancer types, including liver, colon, kidney, lung and melanoma, have shown that JX-594, delivered either directly into tumors or systemically, induces tumor shrinkage and/or necrosis and is well-tolerated by patients. Objective tumor responses have been demonstrated. The trial results suggests that JX-594 has a favorable safety profile with predictable and generally mild side effects that typically include flu-like symptoms that resolve in 48 to 72 hours.
Poxvirus
The poxvirus strain backbone of JX-594 has been used safely in millions of people as part of a worldwide vaccination program. This strain naturally targets cancer cells due to common genetic defects in cancer cells. JX-594 was engineered to enhance this natural safety and cancer-selectivity by deleting its thymidine kinase (TK) gene, thus making it dependent on the cellular TK expressed at persistently high levels in cancer cells. To enhance product efficacy, JX-594 is also engineered to express the GM-CSF protein. GM-CSF complements the cancer cell lysis work of the product candidate, leading to a cascade of events resulting in tumor necrosis, tumor vasculature shutdown and an anti-tumoral immune attack.
Hepatocellular Carcinoma
Hepatocellular carcinoma is the fifth most common cancer worldwide and the third leading cause of cancer death, with over 600,000 new cases diagnosed annually resulting in more than 90 percent mortality. The annual incidence rate in the U.S., Europe, Japan and China are estimated to be 20,000, 55,000, 40,000 and 350,000 patients, respectively. Currently, there is only one approved agent for HCC, a drug called sorafenib (Nexavar?), which is associated with moderate efficacy (tumor response rate of <5%) and a side effect profile that has resulted in discontinuation of use in some patients.
Study HEP007
Clinical investigators enrolled approximately 30 patients at sites in the United States, Canada and South Korea.The data were presented by David Kirn, M.D., president and chief executive officer of Jennerex, today in an oral presentation in the Presidential Symposium of the American Society of Gene and Cell Therapy (ASGCT) Annual Meeting in Seattle, Washington.
Jennerex expect to present further follow-up on the complete trial data set at a medical conference later this year.
A randomized, placebo-controlled Phase IIb clinical trial of JX-594 in patients with hepatocellular carcinoma (HCC) having failed sorafenib(Nexavar?), is planned for initiation in the second half of this year. This trial (TRAVERSE), conducted globally will evaluate survival in advanced HCC patients who have either progressed or exhibited intolerance after treatment with sorafenib, the current standard of care.
“We are extremely encouraged by the promising overall survival results presented today. These results are consistent with a clinically meaningful survival benefit in patients with advanced liver cancer. Given the large global unmet need in this patient population, we are confident to proceed into larger late-stage trials in advanced HCC patients with JX-594,” stated Dr. Kirn. “If a statistically-significant survival benefit with JX-594 is confirmed in larger randomized trials in HCC patients, JX-594 could represent a major new treatment option for these patients.”
