Onxeo S.A., an innovative company specializing in the development of orphan oncology therapeutics, has reported the final data from a study aiming to confirm the mechanism of action of Livatag®, a doxorubicin loaded nanoparticle formulation based on Onxeo's Transdrug™ technology in overcoming cellular resistance in hepatocellular carcinoma (HCC). Livatag® is currently being evaluated in a Phase III trial (ReLive) in patients with advanced HCC, or primary liver cancer.
Results, presented in a poster (Abstract #2143 / Poster #13) by Dr. Graham Dixon, PhD, Onxeo's Chief Scientific Officer, at the American Association for Cancer Research (AACR) Annual Meeting, demonstrated that the bio-distribution of doxorubicin Transdrug™ (Livatag®) nanoparticles showed a preferential affinity for the liver and an increased exposure in plasma compared to free doxorubicin, together supporting the use of Livatag® in the treatment of patients suffering from advanced HCC.
While evaluating the mechanism of action the study showed that the nanoparticle formulation of doxorubicin Transdrug™ (Livatag®) entered into HCC cell lines via passive diffusion and avoided recognition by certain multi-drug resistance (MDR) proteins, (P glycoprotein 1, or Pgp) leading to major accumulation of the drug in the cells and a dramatic increase in cytotoxicity in HCC cell lines compared to free doxorubicin.
Further investigations will be performed to test if doxorubicin Transdrug™ (Livatag®) also overcomes resistance induced by other MDR-related proteins expressed by HCC cells as well as the involvement of the Livatag® nanoparticle "ion pair" in overcoming the efflux-mediated resistance.
Graham Dixon, PhD, Chief Scientific Officer of Onxeo, commented, "These are important findings as they confirm that the underlying mechanism of action of Livatag®'s nanoformulation effectively accumulates doxorubicin specifically in the liver and evades tumor cell resistance mediated by multiple drug resistance MDR efflux pumps, enabling an efficacious and safe approach to cancer treatment. These results further support our ongoing Phase 3 ReLive study of Livatag® for the treatment of patients with advanced HCC, for which we anticipate preliminary data readout mid-2017."
About hepatocellular carcinoma
Hepatocellular carcinoma (HCC) or hepatocarcinoma is the most common of the primary liver cancers (85% to 90%). According to Globocan (2012 data), liver cancer is the sixth most common cancer in terms of incidence (782,000 new cases worldwide each year, 5.6% of all new cancer cases) with the second highest mortality rate (746,000 deaths, 9.1% of the total) after lung cancer. The risk factors are well known: infection by hepatitis viruses (B and C), overconsumption of alcohol (another major cause of cirrhosis) and metabolic diseases, especially obesity, a growing cause of cirrhosis and HCC.