RARE Daily

FDA Places Clinical Hold on UniQure Hemophilia B Gene Therapy Program

December 21, 2020

Rare Daily Staff

The U.S. Food and Drug Administration placed a clinical hold on UniQure’s hemophilia B gene therapy program, including the pivotal, phase 3 HOPE-B study, the company reported.  

Patient dosing is complete in each of UniQure’s three hemophilia B gene therapy studies, and there is no plan to enroll or treat additional patients.

The clinical hold was initiated following the submission of a safety report in mid-December relating to a possibly related serious adverse event associated with a preliminary diagnosis of hepatocellular carcinoma (HCC), a form of liver cancer, in one patient in the HOPE-B trial who was treated with etranacogene dezaparvovec (AMT-061) in October 2019. The patient has multiple risk factors associated with HCC, including a twenty-five-year history of hepatitis C (HCV), hepatitis B virus (HBV), evidence of non-alcoholic fatty liver disease and advanced age. Chronic infections with hepatitis B and C have been associated with approximately 80 percent of HCC cases.

The liver lesion was detected during a routine abdominal ultrasound conducted as part of the required study assessments in patients at one-year post dosing. A full surgical resection of the lesion is scheduled this week that will allow for confirmation of the diagnosis. No other cases of HCC have been reported in UniQure clinical trials conducted in more than 100 patients in hemophilia B and other indications, with some patients dosed more than 10 years ago.

“Patient safety will always be our top priority, and we are working closely with the FDA and our advisors to conduct a thorough investigation into the cause of this event, which we expect to be completed in early 2021,” said Ricardo Dolmetsch, president of research and development at UniQure. “We will investigate whether there is a relationship to treatment. At this time, we do not have adequate data to determine a possible causal relationship, especially in the context of the other known risk factors.”

Hemophilia B is a genetic bleeding disorder caused by mutations in the F9 gene that slows the blood clotting process. People with this disorder experience prolonged bleeding or oozing following an injury or surgery. In severe cases of hemophilia, heavy bleeding occurs after minor trauma or even in the absence of injury. Serious complications can result from bleeding into the joints, muscles, brain, or other internal organs.

Etranacogene dezaparvovec consists of an AAV5 viral vector carrying a gene cassette with the patent-protected Padua variant of Factor IX (FIX-Padua). Etranacogene dezaparvovec has been granted Breakthrough Therapy Designation by the United States Food and Drug Administration and access to Priority Medicine (PRIME) regulatory initiative by the European Medicines Agency. In June 2020, UniQure and CSL Behring entered into a licensing agreement providing CSL Behring with exclusive global rights to etranacogene dezaparvovec.

“All patients in our hemophilia B gene therapy program, including the 54 patients in HOPE-B, will continue to be monitored by their care teams while we gather additional information as rapidly as possible,” said Matt Kapusta, CEO of UniQure. “We do not anticipate any impact to our regulatory submission timeline for the hemophilia B program as a result of this clinical hold.”  

Photo: Matt Kapusta, CEO of UniQure

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