Phase 3 hepatocellular carcinoma fail crushes Onxeo

Onxeo’s Livatag has failed to beat the active control in a phase 3 hepatocellular carcinoma (HCC) trial. The setback wiped about 50% off Onxeo’s share price as investors adjusted to the diminished expectations for the doxorubicin-loaded nanoparticle candidate.

Investigators enrolled about 400 patients with unresectable HCC who were either intolerant to Bayer’s 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, provided it wasn’t Nexavar.

This is why Onxeo says the trial came unstuck. Onxeo has yet to provide a look at the data but the trial’s coordinating investigator said the survival rate in the control arm was “unprecedented.” The patients in this cohort received drugs including the chemotherapies gemcitabine and oxaliplatin. Tyrosine kinase inhibitors were also administered.

Livatag’s efficacy was in the same ballpark as that achieved by these drugs. Onxeo also said its drug “tends to” show similar efficacy to Bayer’s Stivarga, with the caveat that cross-trial comparisons can be unreliable. Bayer won FDA approval in HCC patients previously treated with Nexavar on the strength of a median overall survival of 10.6 months, compared to 7.8 months in the placebo arm.

Onxeo’s trial found no dose-dependent differences between the two Livatag arms.

Assuming the full data matches the narrative presented by Livatag, the trial is likely to present the drug as having similar efficacy as existing drugs. Onxeo said the experimental and control arms had comparable overall tolerability profiles too.

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, we will reinitiate licensing discussion with potential partners based on key study outcomes to define the best path forward,” Onxeo CEO Judith Greciet said in a statement. 

Onxeo looked into outlicensing Livatag last year, at which time it was open to either offloading the drug in return for an upfront fee, milestones and royalties or forming a co-development pact. A deal never materialized. But, armed with the mixed blessing of the phase 3 data, Onxeo now plans to try again.