Trial shows significant survival benefit with oncolytic virus in patients with advanced liver cancer

Jennerex, Inc., a private clinical-stage biotherapeutics company focused on the design, development and commercialisation of first-in-class targeted oncolytic products for cancer, presented on Nov 5 final data from a randomised dose-ranging Phase 2 clinical trial of JX-594 in patients with advanced liver cancer showing a statistically significant benefit in overall survival for the high JX-594 dose group versus the low dose group.

The final data from the HEP007 trial demonstrated that the risk of death for patients who received JX-594 at the high dose was markedly reduced (by nearly 60 percent; hazard ratio = 0.41) when compared to patients randomised to a low dose control (one-tenth of the high dose). The median overall survival for high and low dose groups was 13.8 months versus 6.7 months, respectively (p = 0.029 for superiority of the high dose). The percent of patients alive at one year was 66 percent versus 23 percent in high- and low-dose groups, respectively (Kaplan-Meier estimate). JX-594 was well-tolerated with patients experiencing transient flu-like symptoms that generally resolved within 24 hours. This clinical trial, HEP007, was led by Jennerex in North America and by Green Cross in South Korea and enrolled 30 patients at sites in the United States, Canada and South Korea.

The data were presented on Nov 5 by Tony Reid, M.D., Ph.D., professor of medicine, haematology/oncology, director of clinical investigation, and the tumour growth, invasion and metastasis program, Moores UCSD Cancer Center at the University of California, San Diego. Dr. Reid presented during the late-breaking oral session at the 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in San Francisco, California. The abstract (#LB-1) was entitled “A Randomized, Controlled Phase 2 Clinical Trial of JX-594, a Targeted Multi-Mechanistic Oncolytic Poxvirus, in Patients with Advanced Hepatocellular Carcinoma: Final Data.” A randomised, placebo-controlled Phase 2b clinical trial of JX-594 in patients with hepatocellular carcinoma (HCC) having failed sorafenib (Nexavar®) treatment was recently initiated; this trial (TRAVERSE), conducted globally with Jennerex’s partners, is evaluating survival in advanced HCC patients who have either progressed or exhibited intolerance after treatment with sorafenib, the current standard of care.

“These data showing an improvement in overall survival are very encouraging—particularly when coupled with the favourable tolerability profile of JX-594 experienced in this and prior clinical trials. Another therapeutic option to treat patients with HCC, the third leading cause of cancer death globally, is urgently needed,” stated Dr. Reid, a clinical investigator on the HEP007 clinical trial.

“The strength of these data—showing a statistically significant benefit in overall survival—gives us great confidence in the potential of JX-594 to benefit patients with liver and other types of cancer world-wide,” stated David H. Kirn, M.D., president and chief medical officer of Jennerex. “Based on these clinical data, and clinical data we’ve previously published, we are accelerating the development of JX-594. Together with our partners, we’re initiating a more expansive late-stage TRAVERSE clinical trial of JX-594 in HCC, and we’re moving into Phase 1/2 trials in additional cancer types, including ras mutant and Erbitux-refractory colorectal cancer.”

JX-594: A Multi-Mechanistic Approach To Targeting Cancer

JX-594 is a proprietary, engineered oncolytic virus that is designed to selectively target and destroy cancer cells. JX-594 is designed to attack cancer through three diverse mechanisms of action: 1) the lysis of cancer cells through viral replication, 2) the shutdown of the blood supply to tumours through vascular targeting and destruction, and 3) the stimulation of the body’s immune response against cancer cells, i.e., active immunotherapy. Phase 1 and Phase 2 clinical 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 is well-tolerated by patients (over 120 treated to date).

JX-594 is the most advanced product candidate from Jennerex’s proprietary SOLVE™ (Selective Oncolytic Vaccinia Engineering) platform. SOLVE takes advantage of the natural attributes of poxviruses as well as their ability to be genetically engineered to produce safe, therapeutic viruses that can infect solid tumours both systemically and locally. The vaccinia 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 potentially enhance product efficacy, JX-594 is also engineered to express the immunogenic GM-CSF protein. GM-CSF complements the cancer cell lysis of the product candidate, leading to a cascade of events resulting in tumour necrosis, tumour vasculature shutdown and sustained anti-tumoural immune attack.

Hepatocellular Carcinoma: A Global Unmet Need

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 (tumour response rate of <5%) and a side effect profile that has resulted in discontinuation of use in some patients.

(Source: Jennerex Biotherapeutics)