Dose-Confirmation Study for Hemophilia B Gene Therapy Underway

The first patient has been treated in a phase 2b dose-confirmation study of AMT-061, an investigational gene therapy that has been granted Breakthrough Therapy Designation by the FDA for the treatment of patients with severe and moderately severe hemophilia B.

The treatment is an AAV5-based gene therapy incorporating the Factor IX (FIX)-Padua variant. The phase 2b study is an open-label, single-arm, single-dose trial. Approximately 3 patients will receive a single intravenous (IV) infusion of 2x10¹³ vc/kg and be evaluated for 6 to 8 weeks to assess FIX activity.

“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, MD, PhD, chief medical officer of uniQure, said in a statement.

Hemophilia B is a rare, inherited severe blood clotting disorder caused by a missing or defective FIX protein. FIX-Padua expresses a protein that has been reported to provide an approximate 8- to 9-fold increase in FIX activity compared with the wildtype FIX protein.

Learn more about the hemophilia treatment landscape.

Once the dosing of AMT-061 is confirmed in the phase 2b study, the safety and efficacy of the therapy will be evaluated in the global phase 3 HOPE-B clinical trial. In the HOPE-B trial, 50 adults with severe and moderately severe hemophilia B will receive a single IV of AMT-061 after a 6-month lead-in period, which will establish a baseline control. The trial is expected to start in the first quarter of 2019.

The primary endpoint of the HOPE-B trial is FIX activity level achieved after receiving the therapy and the secondary endpoints will measure annualized FIX replacement therapy use rate and annualized bleed rate.

“As a one-time administered therapy, AMT-061 has the potential to transform the treatment paradigm for hemophilia B patients,” said Annette von Drygalski, MD, 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.”