AMT-061 uses a viral vector to deliver the gene for a mutated clotting factor IX (FIX), which is also known as the Padua variant (FIX-Padua). This man-made mutation leads to a higher production of FIX, which is compromised in hemophilia B patients.
“AMT-061 has the potential to be a major advancement in gene therapy for patients affected by hemophilia B,” Steven Pipe, MD, pediatric medical director of the hemophilia and coagulation disorders program at the University of Michigan and principal investigator of the HOPE-B clinical trial, said in a press release.
“A one-time treatment, such as AMT-061, could be life-changing for these patients, many of whom struggle to manage ongoing challenges, including compliance with frequent infusions, and recurrent episodes of bleeding,” he added.
The Phase 3 HOPE-B trial (NCT03569891) is a multi-center, open-label, single-dose study evaluating the safety and effectiveness of AMT-061.
Researchers hope to recruit a total of 56 severe or moderately severe adult hemophilia B patients for the trial. Initially, participants will be followed for six months while on their standard of care therapy to establish baseline control of factor IX activity levels.
After that, they will receive a single intravenous administration of AMT-061. Dosing is expected to begin early in 2019.
The trial’s primary goal is the assessment of FIX activity levels following the single-dose administration of AMT-061.
Secondary endpoints will compare the annual bleeding rate between standard of care treatment and AMT-061 as well as annualized factor IX replacement therapy use rate. A five-year follow-up is also planned to assess any adverse events.
UniQure is also initiating a short, Phase 2b dose-confirmation trial of AMT-061 (NCT03489291) in just three adult patients, also with severe or moderately severe hemophilia B. Enrollment is expected to begin this month (July).
Participants will receive a single dose of AMT-061. They will be followed for six to eight weeks to determine FIX activity levels and to confirm the dose of AMT-061 for the Phase 3 HOPE-B study. The three dose-confirmation trial participants will continue to be observed for one year.
“We are delighted to have enrolled the first patient in this Phase III pivotal study of a gene therapy for patients with hemophilia B,” said Steve Zelenkofske, DO, chief medical officer at uniQure. “This represents a significant milestone for uniQure as we advance a potentially best-in-class gene therapy for patients with this life-altering disorder.”
“In addition to advancing our pivotal trial, we have also initiated patient recruitment for our Phase IIb dose-confirmation study and expect to commence enrollment in July. We look forward to announcing top-line FIX data from the dose-confirmation study before the end of the year,” Zelenkofske added.
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 of its sister gene therapy, AMT-060.
Also last year, the European Medicines Agency (EMA) granted Priority Medicines (PRIME) designation to AMT-061, which helps accelerate the development of medicines that target an unmet medical need.