On April 18, 2016 Onxeo S.A. (Euronext Paris, Nasdaq Copenhagen: ONXEO), an innovative company specializing in the development of orphan oncology therapeutics, 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) (Press release, Onxeo, APR 18, 2016, View Source [SID:1234511024]). Livatag is currently being evaluated in a Phase III trial (ReLive) in patients with advanced HCC, or primary liver cancer.
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Results, presented today 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) (Free AACR Whitepaper) 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."