FDA Removes Hold on uniQure Hemophilia B Gene Therapy Program

The FDA hold was announced in December 2020 following the diagnosis of one patient with hepatocellular carcinoma in the HOPE-B pivotal trial.

Gene therapy company uniQure has announced that the FDA has removed a hold on their hemophilia B gene therapy program after determining that the company addressed all concerns with a patient diagnosed with hepatocellular carcinoma (HCC) in the HOPE-B pivotal trial, which is investigating etranacogene dezaparvovec (AMT-061).

AMT-061 is an AAV5 viral vector carrying a gene cassette with the Padua variant of factor IX. It has been granted Breakthrough Therapy Designation by the FDA as well as access to Priority Medicine regulatory initiative by the European Medicines Agency, according to a press release.

The company announced the FDA hold in December 2020, following the diagnosis of a patient with HCC. According to a press release, the patient had multiple risk factors for HCC, including a 25-year history of hepatitis C and a history of hepatitis B, both of which have been associated with approximately 80% of HCC cases.

“Patient safety is our top priority, and we are grateful to our advisors and the FDA for their help in resolving this clinical hold,” said Ricardo Dolmetsch, PhD, president of research and development at uniQure, in the press release. “Our comprehensive investigation showed that AMT-061 is very unlikely to have contributed to the HCC in our patient.”

Following a surgical resection of both the tumor and adjacent liver tissue, multiple analyses found that the patient’s tissue sample was extremely rare and accounted for approximately 0.027% of the cells in the sample. The integration events were distributed randomly across the genome, and there was no evidence of clonal expansion or any dominant integration event.

Furthermore, whole genome sequencing confirmed that the tumor had genetic mutations characteristic of HCC and are independent of vector integration. Gene expression analysis and adjacent tissue also suggested a precancerous state in the liver that may have predisposed the patient to HCC, according to the press release.

All patients in the uniQure gene therapy program, including 54 patients in HOPE-B, have had abdominal ultrasounds performed 1 year after dosing, and each will continue to be monitored by their care teams. Patients will continue to receive abdominal ultrasounds every 6 months and no other cases of HCC have been reported in uniQure clinical trials conducted in more than 100 patients with hemophilia B and other indications.


uniQure Announces FDA Removes Clinical Hold on Hemophilia B Gene Therapy Program [news release]. Euroland; April 26, 2021. https://tools.eurolandir.com/tools/Pressreleases/GetPressRelease/?ID=3902770&lang=en-GB&companycode=nl-qure&v=ticker. Accessed April 30, 2021.