First Hemophilia B Patient Treated with AMT-061 in Phase 2b Trial

uniQure has treated the first patient in a Phase 2b dose-confirmation study of its investigational gene therapy, AMT-061, for people with severe and moderately severe hemophilia B. The trial is still recruiting participants.

AMT-061 uses a viral vector, AAV5, to deliver the gene for a mutated clotting factor IX (FIX) called the Padua variant (FIX-Padua). This manmade mutation leads to an approximate increase in FIX activity of eight to nine times, which is compromised in hemophilia B patients.

In this open-label, single-dose, single-arm, Phase 2b trial (NCT03489291), three participants with severe or moderately severe hemophilia B will receive a single dose of AMT-061 and will be monitored for therapy tolerance plus potential immediate complications at the trial site for 24 hours. After that, patients will be followed for one year.

The study’s primary endpoint is to confirm that a single dose of AMT-061 will result in FIX activity levels of 5% or more at six weeks after dosing. People with severe hemophilia B have less than 1% of FIX activity.

Ultimately, the purpose of this Phase 2b trial is to confirm the dose of AMT-061 for the Phase 3 HOPE-B trial (NCT03569891) focused on the safety and effectiveness of uniQure’s gene therapy in severe and moderately severe hemophilia B.

For the Phase 3 trial, researchers plan to recruit 50 adult patients; enrollment has already started. Dosing is expected to begin early in 2019.

“The initiation of the AMT-061 dose-confirmation study is an important step toward our goal of advancing a potentially life-changing treatment for patients with hemophilia B,” Robert Gut, an MD and PhD, the chief medical officer of uniQure, said in a press release.

“I am extremely proud of the efforts made by the uniQure team to initiate this study, the objective of which is to demonstrate meaningful increases in FIX activity using the Padua variant and confirm dosing for the HOPE-B pivotal trial initiated this past June,” Gut said. “We look forward to completing patient enrollment shortly and providing top-line data before the end of the year.”

Annette von Drygalski, MD, associate clinical professor at the University of California San Diego and director of its hemophilia and thrombosis treatment center, said, “As a one-time administered therapy, AMT-061 has the potential to transform the treatment paradigm for hemophilia B patients.”

“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,” she added.

“I greatly appreciate the opportunity to participate in the AMT-061 clinical program and view the initiation of the Phase 2b and Phase 3 studies as important milestones in the development of this potentially important therapy for patients with hemophilia B.”

Last year, AMT-061 was granted breakthrough therapy designation by the U.S. Food and Drug Administration based on results from the Phase 1/2 study (NCT02396342) of its sister gene therapy, AMT-060.

In addition, the European Medicines Agency granted priority medicines (PRIME) designation to AMT-061, which expedites the therapy’s assessment and can potentially allow the treatment to reach patients sooner.