FDA lifts clinical hold on uniQure's gene therapy amid cancer concerns; shares jump

After four months of hand-wringing and a deep investigation into how a patient was diagnosed with cancer after getting uniQure’s hemophilia gene therapy, the FDA is allowing the trial to continue.

In December, the FDA put uniQure’s hemophilia B gene therapy on clinical hold in response to a case of hepatocellular carcinoma (a form of liver cancer) in a patient in the pivotal trial of etranacogene dezaparvovec.

UniQure and partner CSL Behring 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. 

Then, back in March, uniQure shared the findings of an investigation into the liver cancer case. The investigation found its gene therapy was “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% in the patient’s tissue sample. The integration events that were present were randomly distributed. There were no signs of clonal expansion nor any dominant integration event. None of the integrations happened at sites linked to the development of hepatocellular carcinoma.

RELATED: UniQure/CSL hit by FDA clinical hold for hem B gene therapy program after liver cancer find

At the time, the findings diminished 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.

Now, it seems the biotech has got the FDA back on board. The agency has removed the hold on the program “after determining the company satisfactorily addressed all issues identified by the FDA related to a single patient diagnosed with hepatocellular carcinoma (HCC) in the HOPE-B pivotal trial,” the biotech said in a statement. It gave no other details as to why the FDA made this decision.

“Patient safety is our top priority, and we are grateful to our advisors and the FDA for their help in resolving this clinical hold,” stated Ricardo Dolmetsch, Ph.D., president of research and development at uniQure. “Our comprehensive investigation showed that AMT-061 (etranacogene dezaparvovec) is very unlikely to have contributed to the HCC in our patient. We look forward to announcing top-line 52-week data from the HOPE-B pivotal trial later this quarter.”

Its shares jumped 10% premarket on the news.