UniQure Reports Positive, Initial Topline Data of Hemophilia B Gene Therapy


Rare Daily Staff

UniQure said initial clinical data from its phase 2b dose-confirmation study of AMT-061, its gene therapy for the treatment of patients with severe and moderately severe hemophilia, showed that therapeutic levels of factor IX (FIX) activity have been achieved and sustained in all three patients at six weeks after a single administration.

The phase 2b study of AMT-061 is an open-label, single-dose, single-arm, multi-center trial being conducted in the United States. Three patients with severe hemophilia were enrolled in this study and received a single intravenous infusion of the therapy. The objective of the study is to evaluate the safety and tolerability of AMT-061 and confirm the dose based on FIX activity at six weeks after administration.

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.

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

Data from the study show that all three patients experienced increasing and sustained FIX levels after a one-time administration of AMT-061. Six weeks after administration mean FIX activity for the three patients was 31 percent of normal, exceeding threshold FIX levels generally considered sufficient to significantly reduce the risk of bleeding events.

“We are highly encouraged by these early data, where all patients achieved therapeutic levels of FIX activity,” stated Robert Gut, chief medical officer of UniQure.  “Based on the long-term FIX data from our phase 1/2 trial of AMT-060, where we saw FIX activity levels continue to increase beyond the levels achieved at six to ten weeks, we are hopeful that we will continue to see similar trends in these patients.”

Over the 24 weeks of combined observation among three patients, no patient experienced a material loss of FIX activity, reported any bleeding events, or required any infusions of FIX replacement therapy. AMT-061 has been well-tolerated, with no significant adverse events reported and no patients requiring any immunosuppression therapy. One patient experienced a mild, asymptomatic increase in liver enzyme levels, which resolved quickly without any additional treatment.

“The transition to our patent-protected Padua construct with AAV5 was undertaken with the goal of providing all hemophilia B patients an opportunity to access a one-time treatment capable of increasing FIX activity to potentially functionally curative levels without the risk of immune responses that may lead to a loss of efficacy,” stated Matt Kapusta, CEO of UniQure.

UniQure expects to submit data from the phase 2b study to the FDA and EMA by the end of the year. The study’s Data Monitoring Committee will meet before the end of the year to evaluate and potentially confirm the dose for the phase 3 study.  The company expects to initiate the dosing phase of its phase 3 pivotal study in the first quarter of 2019.


November 15, 2018
Photo: Robert Gut, chief medical officer of UniQure

Filed Under: Business, Drug Development

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