UniQure Reports Positive Top-Line Results of Late-Stage Study of Hemophilia B Gene Therapy

Rare Daily Staff

UniQure reported positive top-line data from its pivotal, late-stage study of its experimental gene therapy etranacogene dezaparvovec for the treatment of patients with severe and moderately severe genetic bleeding disorder hemophilia B.

This is the first data set to be reported from a phase 3 gene therapy study in hemophilia B and, with 54 patients, the largest set of patients receiving a single gene therapy investigational product to be reported to date. The data were published as a late-breaking abstract at the 62^nd Annual Meeting of the American Society of Hematology (ASH) and will be featured as an oral presentation in the conference on December 8, 2020.

Hemophilia B is a rare bleeding disorder caused by mutations in the F9 gene resulting in insufficient levels of the blood clotting protein factor IX. Symptoms can range from mild to severe depending on the level of factor IX in the blood, and can range from prolonged bleeding after injury to frequent spontaneous bleeds into the muscles and joints and organs in severe cases that cause pain and other problems. Bleeding in the brain can lead to death if untreated.

The company said the gene therapy led to sustained increases of Factor IX (FIX) to functionally-curative levels capable of eliminating the need for regular infusions to control and prevent bleeding episodes.

“These data also demonstrate the potential to achieve clinical benefit in patients with a range of pre-existing neutralizing antibodies representative of the general population,” said Ricardo Dolmetsch, president of research and development at UniQure. “The ability to dose a gene therapy in patients with pre-existing neutralizing antibodies has not been demonstrated for any other gene therapy and illustrates the potentially unique ability of our AAV5 platform to address the needs of a broad set of patients living with hemophilia B and other disorders.”

The pivotal phase 3 study was an open-label, single-dose, single-arm, multi-national trial in adult males with severe or moderately severe hemophilia. All patients required prophylactic routine FIX replacement prior to entering the clinical trial, and patients were not excluded from the trial based on pre-existing neutralizing antibodies (NAbs) to AAV5.

AMT-061 met the first primary endpoint with mean FIX activity of 37.2 percent of normal at 26 weeks. Other co-primary endpoints in the HOPE-B trial are FIX activity at 52 weeks after dosing and an annualized bleeding rate at 52 weeks. Data also show that 72 percent of patients reported no bleeding events and that there was no correlation between FIX activity and patients with high titers (up to 678.2) of pre-existing neutralizing antibodies to AAV5. AMT-061 was generally well-tolerated with no treatment-related serious adverse events.

During the 26-week period after dosing, 72 percent of patients (39/54) reported no bleeding events. Fifteen patients reported a total of 21 bleeds. Mean annualized usage of FIX replacement therapy, a secondary endpoint in the clinical trial, declined by 96 percent.

“We believe that etranacogene dezaparvovec has the potential to be a first- and best-in-class gene therapy for patients with hemophilia B,” said Matt Kapusta, CEO of UniQure. “Based on interactions with the FDA and EMA, we plan to incorporate FIX activity and bleeding rates at 52 weeks as additional co-primary endpoints in the study. We look forward to holding our pre-BLA meeting with the FDA and completing the last patient’s 52-week follow-up visit in the first quarter of 2021.”

Photo: Matt Kapusta, CEO of UniQure