The US Food and Drug Administration (FDA) has removed a clinical hold on Dutch biotech uniQure’s haemophilia B gene therapy, following concerns over a case of cancer in a patient in a pivotal trial.
In December 2020, the FDA placed a hold on uniQure’s haemophilia B clinical programme following the diagnosis of hepatocellular carcinoma (HCC) – a type of liver cancer – in a patient in the HOPE-B trial evaluating AMT-061 (etranacogene dezaparvovec).
In a statement, uniQure said that the patient diagnosed with HCC had ‘multiple risk factors’ associated with this type of cancer. This included a 25-year history of hepatitis C (HCV) as well as a history of hepatitis B (HBV). Chronic infections with both HCV and HBV are associated with around 80% of HCC cases.
Multiple analyses, following a surgical resection of both the patient’s tumour and adjacent liver tissue, showed that AAV vector integration in the tissue sample was ‘extremely rare’, accounting for 0.027% of the cells in the sample.
The integration events that were present were randomly distributed, the company added, with no signs of clonal expansion or any dominant integration event.
Whole genome sequencing of the tumour also confirmed that it had genetic mutations characteristic of HCC, independent of vector integration.
UniQure noted that a gene expression analysis of the tumour and adjacent tissue suggested a precancerous state in the liver that could have predisposed the patient to developing HCC.
“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, president of research and development at uniQure.
“Our comprehensive investigation showed that AMT-061 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,” he added.
UniQure added that all patients in its haemophilia clinical programme have abdominal ultrasounds performed one year after dosing, with patients continuing to receive this test every six months.
AMT-061 has been granted breakthrough therapy designation by the FDA and a priority medicine (PRIME) designation by the European Medicines Agency (EMA).