Patient Enrollment Ongoing in Phase 3 Trial of AMT-061 for Hemophilia B, uniQure Says in Update

uniQure is continuing to enroll participants for its global Phase 3 trial (NCT03569891) testing the potential gene therapy AMT-061 in men with severe or moderately severe hemophilia B, according to an update from the company.

In addition, uniQure announced that three patients included in a Phase 2b trial (NCT03489291) of AMT-061 have already been treated.

“We achieved a number of important milestones so far this year, including the initiation of our global HOPE-B pivotal trial in hemophilia B [and] the dosing of three patients in our dose-confirmation study of AMT-061,” Matt Kapusta, uniQure’s CEO, said in a press release.

Hemophilia B is characterized by a missing or defective factor IX (FIX), a clotting protein. AMT-061 uses a viral vector to deliver a gene that generates a mutated FIX, also known as the Padua variant (FIX-Padua), for higher production of FIX.

In 2017, the U.S. Food and Drug Administration granted breakthrough therapy designation to AMT-061 based on results from the Phase 1/2 study (NCT02396342) of its sister gene therapy, AMT-060. AMT-061 and AMT-060 only differ in a small variation in the gene sequence for FIX.

The open-label Phase 3 HOPE-B trial (NCT03569891) is intended to test the safety and effectiveness of AMT-061 in adult men with hemophilia B. The trial includes a six-month phase to collect baseline data, with patients serving as their own controls while on their standard-of-care therapy. This will be followed by treatment with a single intravenous (IV; into the vein) administration of AMT-061.

The study’s primary goal is to assess FIX activity levels following administration of AMT-061. Annual bleeding rate, annualized factor IX replacement therapy use rate, and adverse events will also be analyzed.

uniQure expects to start dosing patients in the first quarter of 2019. The trial has new enrollment sites open in the U.S. and Europe. More information on patient enrollment — for a planned total of 56 — can be found here.

Additionally, three patients with severe or moderately severe hemophilia B have been treated in the Phase 2b study of AMT-061, receiving a single IV infusion of AMT-061 at 2×1013 vc/kg and are currently under evaluation. Data at six to eight weeks will be used to evaluate FIX activity and confirm the dose that will be used in HOPE-B.

Among its expected near future milestones, uniQure plans to reveal top-line data from this Phase 2b trial by the end of the year and present long-term durability, safety and efficacy results from the Phase 1/2 trial study of AMT-060 at the upcoming 2018 American Society of Hematology Annual Meeting, taking place in early December in San Diego.

The company will host a Research & Development Day from 8:30 a.m. to 12:00 p.m. EST Nov. 19, which will be live-streamed under the investor relations section of uniQure’s website. The program covers uniQure’s expanded early stage pipeline as well as advances in its technology platform.

“In the new year, we look forward to commencing patient dosing in the treatment phase of our HOPE-B pivotal study,” Kapusta said. ”We also are excited to host a Research & Development Day on November 19, 2018 featuring our newest gene therapy research programs and our recent progress advancing important new technologies.”

In 2018, uniQure also completed a study in primates testing the safety and toxicology of AMT-130, a potential gene therapy for Huntington’s. The company aims to start the first clinical trial of this therapy in 2019.

Along with Bristol-Myers Squibb, uniQure also recently completed a heart function study of the gene therapy candidate AMT-126 in an animal model of congestive heart failure. After a lack of heart function benefit was observed at six months, the companies have decided to switch cardiovascular target, discontinuing their work on the S100A1 gene.

At the recent European Society of Gene and Cell Therapy 26th Annual Congress in Lausanne, Switzerland, uniQure presented data showing a marked increase in protein production with a next-generation promoter for liver-directed gene therapies. It also shared its development of a new tank reactor process with the potential to significantly increase manufacturing capacity.

Full details on uniQure’s announcements are available here.