Serious adverse effects reported in adults

Very limited evidence suggests that, although low levels anticipated in milk due to the drug’s properties, the prolonged persistence of an active metabolite means that the potential risk to the infant outweighs benefits of breastfeeding

Mar 18: Company to conclude the development of Livatag in liver cancer according to 2017 annual report [11].

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May 14: Received Fast Track designation from the FDA for the treatment of hepatocellular carcinoma (primary liver cancer) after treatment with Sorafenib. [5]

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Apr 15: Onxeo announced it is seeking partners for the development of Livatag® [6].

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Oct 04: Granted orphan drug status in the EU for treatment of hepatocellular carcinoma [2].

HCC is the most common type of primary liver cancer. In the UK there are about 1,500 deaths per year from HCC. It is thought that HCC may be diagnosed more frequently in the UK over the next few years due to the hepatitis C epidemic

01. Doxorubin Transdrug is presented in the form of nanoparticles delivered via hepatic intra-arterial route. (1)

02. May 12: BioAlliance Pharma initiates the PIII ReLive trial. This international, randomised trial uses doxorubicin Transdrug® formulation (Livatag®) in the treatment of approximately 400 pts with hepatocellular carcinoma, resistant or intolerant to sorafenib. As of May 2012, approximately 15 French sites have been initiated for screening and enrolment of pts. The trial will extend to about 30 sites in France and abroad [3].

03. Dec 13: The PIII study registered with EU Clinical Trials Register: EudraCT Number: 2011-002843-92 [4]

04. Apr 14: The Data Safety and Monitoring Board for the ReLive PIII trial has recommended continuing the study without modification, based on its positive assessment of all safety data of Livatag®. More than 25% of the target number of patients has been enrolled: The trial is still expanding in Europe and implementation of investigator centres is ongoing in the US. Recruitment should be completed end of 2015 for expected data end of 2016 [5].

05. Mar 15: Onxeo announced that approximately 40% of pts in the pivotal PIII ReLive trial (NCT01655693) have been randomised and it is progressing as planned. Enrolment completion and announcement of results are still expected in 2015 and 2016 [6].

06. Jan 16: NCT01655693 (ReLIVE) is still recruiting patients and is not expected to complete until Dec 17 [7]. In Oct 15 the Data Safety Monitoring Board (DSMB) recommended the study continue without modification [8].

07. Dec 16: NCT01655693 Estimated Primary Completion Date now July 2017 [9]

08. Sep 17: Livatag fails to beat the active control in a PIII trial. Investigators enrolled about 400 patients with unresectable HCC who were either intolerant to Nexavar or had progressed after treatment with a regimen featuring the kinase inhibitor. Two-thirds of the participants received Livatag. The rest were given whatever cancer therapy the physician chose, except Nexavar. The survival rate in the control arm was unprecedented. The patients in this cohort received drugs including gemcitabine and oxaliplatin, plus tyrosine kinase inhibitors. Livatag efficacy was in the same ballpark as that achieved by these drugs. There were no dose-dependent differences between the two Livatag arms. That appears to leave little scope for Onxeo to differentiate Livatag, aside from the fact it was given as a monotherapy and the control arm featured whatever regimen the investigator picked. But the French biotech nonetheless thinks it can make money from the drug. Once the Relive data are fully analyzed, they will reinitiate licensing discussion with potential partners based on key study outcomes to define the best path forward [11].

NIHR