UniQure gene therapy 'highly unlikely' to be liver cancer trigger

An independent investigation has found uniQure’s hemophilia B gene therapy is “highly unlikely” to have caused the liver cancer developed by a recipient of the investigational candidate.

In December, the FDA put uniQure’s hemophilia B gene therapy on clinical hold in response to a case of hepatocellular carcinoma in a patient in the pivotal trial of etranacogene dezaparvovec. UniQure had already completed dosing in the affected studies, but the safety concern threatened the chances of the therapy in an indication targeted by Pfizer and Spark Therapeutics' fidanacogene elaparvovec.  

Now, uniQure has shared the findings of an investigation into the liver cancer case. The investigation determined the gene therapy is highly unlikely to have triggered the cancer after uncovering multiple pieces of evidence that point to other causes. Bluebird bio recently reported a similar outcome after assessing a case of cancer in a recipient of its sickle cell disease gene therapy. 

UniQure said cells with AAV vector integration accounted for 0.027% if the patient’s tissue sample. The integration events that were present were randomly distributed. There were no signs of clonal expansion or any dominant integration event. None of the integrations happened at sites linked to the development of hepatocellular carcinoma.

The findings diminish concerns that the gene therapy caused the liver cancer. Other analyses provide evidence that other factors drove development of the tumor. The patient’s tumor had several genetic mutations characteristic of hepatocellular carcinoma and unrelated to vector integration. Analyses of the tumor and adjacent tissue suggest the liver was in a precancerous state.

That state is consistent with factors that put the patient at greater risk of hepatocellular carcinoma. The patient has a history of hepatitis B and C, evidence of nonalcoholic fatty liver disease and other risk factors associated with the cancer. Generating further evidence that those factors are the likely cause of the cancer positions uniQure to push ahead with plans to get the gene therapy to market. 

“We are prepared to discuss with the FDA the recently submitted analyses and the status of the clinical hold as expeditiously as possible. As stated previously, we do not anticipate any impact to the HOPE-B pivotal study or our regulatory submission timeline as a result of the clinical hold,” uniQure CEO Matt Kapusta said in a statement.

UniQure presented top-line data from the pivotal study in December linking its gene therapy to an 83% reduction in bleeding events. The biotech is set to publish more data in the second quarter. A deal with CSL Behring could clear antitrust review and close around the same time.