Pexastimogene devacirepvec (Pexa-Vec) is a proprietary, oncolytic immunotherapy designed to attack cancer through three diverse mechanisms of action: 1) Rapid de-bulking of tumors via direct killing of tumor cells 2) Activation of an antivascular effect with rapid tumor vascular knockout and 3) Induction of a durable immune response. Pexa-Vec exploits specific genetic features in cancer cells to replicate and lyse the cells, including an activated EGFR-ras signaling pathway, cell cycle activation and the loss of cellular interferon defenses. Pexa-Vec was engineered from vaccinia vaccine, which has been safely used for decades as a vaccine in healthy individuals. This attenuated form of vaccinia, armed with a GM-CSF gene that promotes an immune response, was designed to selectively replicate in and destroy tumors, and stimulate the immune system to attack the patient's cancer, thereby offering an "off the shelf" immunotherapy. Pexa-Vec exploits the unique characteristics of vaccinia, including its stealth EEV form, which allows the virus to survive in the bloodstream in the presence of neutralizing antibodies, leading to its ability to be administered both intravenously (IV) and intratumorally (IT).
Unlike many targeted therapies that rely on a single target, Pexa-Vec is applicable to multiple solid tumor targets (i.e. broad spectrum efficacy potential). Phase 1 and Phase 2 clinical trials in multiple cancer types have shown that Pexa-Vec, delivered either directly into tumors or intravenously, induces tumor shrinkage, necrosis and is well-tolerated by patients. Objective tumor response has been demonstrated in a variety of cancers including liver, colon, kidney, lung and melanoma. Importantly, Pexa-Vec has also demonstrated an excellent tolerability profile to date in multiple clinical trials.
In February 2013, final data from a 30-patient, randomized dose-comparison Phase 2 clinical trial of Pexa-Vec in advanced hepatocellular carcinoma (HCC) patients was published in Nature Medicine , demonstrating a statistically significant dose-dependent overall survival benefit with 14.1 months median overall survival for the high-dose group compared to 6.7 months for the low-dose group (p-value = 0.02). This was the first randomized clinical trial of an oncolytic immunotherapy demonstrating significantly prolonged overall survival. Pexa-Vec was well-tolerated with patients experiencing transient flu-like symptoms that generally resolved within 24 hours. A Phase 2b multinational trial (TRAVERSE) is now underway and is designed to enroll 120 patients with advanced liver cancer who have failed sorafenib (Nexavar®) therapy. For more information about any of the Pexa-Vec clinical trials, please visit our clinical trial page.
Transgene (NYSE Euronext Paris: FR0005175080), a bio-pharmaceutical company specialized in the development of immunotherapeutic products, holds an exclusive license to develop and commercialize JX-594 in Europe and neighboring countries. Other regional licenses are held by Lee's Pharmaceutical Ltd. for China and Green Cross Corporation for South Korea. Jennerex has not licensed rights in the United States or Japan.