Investigation Finds Hemophilia Gene Therapy Likely Did Not Cause Hepatocellular Carcinoma

An investigation found that etranacogene dezaparvovec was unlikely to have caused a case of hepatocellular carcinoma (HCC) in a participant of the HOPE-B trial, which is evaluating the gene therapy in patients with hemophilia B.

In December 2020, following a report of a serious adverse event associated with HCC in a patient enrolled in the HOPE-B trial, the U.S. Food and Drug Administration (FDA) placed a clinical hold on manufacturer uniQure’s gene therapy for hemophilia B. The patient was found to have multiple risk factors for HCC, including a history of hepatitis B and C, evidence of nonalcoholic fatty liver disease, smoking history, family history of cancer, and advanced age. The lesion and adjacent liver tissue were analyzed to determine whether etranacogene dezaparvovec was integrated into the lesion and whether the integration caused the cancer to develop.

“The external lab analyzed more than 220,000 cells from the tissue sample and identified 60 cells with random integration events that have no known association with the development of HCC,” said Ricardo Dolmetsch, president of research and development at uniQure. “Moreover, whole genome sequencing of the tumor showed that this patient had large abnormalities on chromosomes 1 and 8 that are commonly associated with HCC, as well as mutation of TP53 and several other potentially oncogenic genes. Taken together, the findings from this investigation strongly suggest that etranacogene dezaparvovec did not contribute to this case of HCC.

All patients who had been receiving etranacogene dezaparvovec, including the 54 patients in the HOPE-B trial, have had abdominal ultrasounds and continue to be monitored. No other cases of HCC have been reported.

Mr. Dolmetsch added, “We have now shared these data with the FDA and are prepared to have further communications regarding the status of the clinical hold in the second quarter of 2021. We also expect to submit the data for presentation at an upcoming industry conference yet to be determined.”

Source: uniQure press release, March 29, 2021.