Date: 2016-09-12
Type of information: Results
phase: preclinical
Announcement: results
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 September 12, 2016, Onxeo announced data from 2 in vivo studies of the Livatag® preclinical plan confirming that the nanoparticle formulation meets the pharmacological requirements for a hepatocellular carcinoma (HCC) treatment and, furthermore, that the combination of Livatag® with immunotherapy produces an enhanced efficacy effect, validating Onxeo’s comprehensive strategy to explore further potential indications for its key product candidate.
The studies were performed in an orthotopic (implantation of tumor cells into the liver of mice) HCC model
in immune-competent mice. Results demonstrate that Livatag® generates a 12-fold increase in exposure in the tumor tissue within the liver compared to free doxorubicin, without increasing the drug’s exposure in the heart or other vital organs. These findings complete, and go beyond, data from a mechanistic study of Livatag® previously reported at the 2016 American Association for Cancer Research (AACR) Annual Meeting that revealed that the distribution of Livatag® nanoparticles in healthy liver was approximately six times higher compared to free doxorubicin, which indicate that Livatag® nanoparticles have a preferential affinity for and are able to target the liver and more particularly, the liver tumor tissue.
As part of this program, Onxeo has also been exploring the potential of Livatag® when administered with
emerging immuno-oncology agents of various classes, such as PD-1 and CTLA-4 checkpoint inhibitors currently in development. A current study demonstrates that Livatag® produces an enhanced effect in tumor response (reduction in tumor volume) when given in combination with immuno-oncology agents in the orthotopic HCC model. Specifically, Livatag® co-administration with antibodies is associated with a positive increase in circulating T-cell populations, which is consistent with the observed reduction in tumor volume.
