Rare Daily Staff

UniQure said that it has treated the first patient in its phase 2b dose-confirmation study of AMT-061, an experimental AAV5-based gene therapy incorporating the FIX-Padua variant for the treatment of patients with severe and moderately-severe hemophilia B.

Hemophilia B is a rare genetic bleeding disorder that results in a deficiency of factor IX, a blood clotting factor. People with hemophilia B are at risk for excessive and recurrent bleeding from modest injuries, which have the potential to be life-threatening. In severe cases, people with the condition can bleed spontaneously into their muscles or joints. In rare cases, they can bleed into the intracranial space, where bleeding can be fatal.

AMT-061 consists of an AAV5 viral vector carrying a gene cassette with the Padua variant of Factor IX (FIX-Padua). FIX-Padua has been reported to provide an approximate 8 to 9-fold increase in FIX activity compared to the wild-type FIX protein, as used in the company’s earlier version AMT-060. AAV5-based gene therapies have been demonstrated to be safe and well-tolerated in multiple clinical trials, including three UniQure trials conducted in 22 patients in hemophilia B and other indications.

The phase 2b dose-confirmation study is an open-label, single-arm, single-dose trial being conducted in the United States. Approximately three patients are expected to receive a single intravenous infusion and be evaluated for a period of approximately six to eight weeks to assess Factor IX (FIX) activity.

Patient enrollment is also underway in the global Phase III HOPE-B clinical trial to evaluate the safety and efficacy of AMT-061. Approximately 50 adult hemophilia B patients classified as severe and moderately-severe will be enrolled in a six-month observational period during which time they will continue to use their current standard of care to establish a baseline control. After the six-month lead-in period, patients will go on to receive a single intravenous administration of AMT-061. Dosing of patients in the HOPE-B pivotal trial is expected to start early in the first quarter of 2019.

AMT-061 has been granted Breakthrough Therapy Designation by the United States Food and Drug Administration and access to Priority Medicines (PRIME) regulatory initiative by the European Medicines Agency.

“As a one-time administered therapy, AMT-061 has the potential to transform the treatment paradigm for hemophilia B patients,” said Annette von Drygalski, associate clinical professor at the University of California San Diego and director of its hemophilia and thrombosis treatment center. “By incorporating both AAV5 and the FIX-Padua variant, AMT-061 has the potential to deliver clinically relevant increases in FIX activity with low risk of cellular immune responses, which could expand patient eligibility for treatment with gene therapy.”

August 23, 2018
Photo: Annette von Drygalski, associate clinical professor at the University of California San Diego