Date: 2016-04-18
Type of information: Presentation of results at a congress
phase:
Announcement: presentation of results at the American Association for Cancer Research (AACR) Annual Meeting
Company: Onxeo (France)
Product: Livatag® (doxorubicin Transdrug®)
Action
mechanism: antineoplastic antibiotic. Livatag® (Doxorubicin Transdrug™) is a doxorubicin formulation in the form of lyophilized nanoparticles of polyisohexylcyanoacrylate (PIHCA).This new therapeutic approach allows drug resistance to be avoided by shortcircuiting the mechanisms of multi-drug resistance developed by tumor cells through the masking of the anticancer agent. Acting as a ‘Trojan horse,’ the nanoparticle formulation avoids rejection of doxorubicin outside the cell so that it can exert its cytotoxic action. By specifically targeting tumor cells in the liver and overcoming resistance to doxorubicin, Livatag® represents a significant breakthrough in the treatment of this cancer.
Disease: hepatocellular carcinoma
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On April 18, 2016, Onxeo 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. Livatag® is currently being evaluated in a Phase III trial (Relive) in patients with advanced hepatocellular carcinoma. 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 hepatocellular carcinoma. While evaluating the mechanism of action the study showed that the nanoparticle formulation of doxorubicin Transdrug™ (Livatag®) entered into hepatocellular carcinoma 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 hepatocellular carcinoma 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.
Onxeo anticipate preliminary data of the Phase 3 ReLive study of Livatag® mid-2017.
(Dixon, G. et al. “Mechanistic study of the relative cytotoxicity of doxorubicin loaded nanoparticle formulation compared to free doxorubicin in hepatocellular carcinoma cell lines.” Abstract #2143 / Poster #13. Presented in a poster session at the American Association for Cancer Research (AACR) Annual Meeting. 18 April 2016. New Orleans, Louisiana, USA.)
