AMT-061 Increases FIX Activity, Prevents Bleeds in Severe Hemophilia B Patients, Phase 2b Data Show

A single infusion of AMT-061 (etranacogene dezaparvovec), uniQure’s experimental gene therapy for the treatment of hemophilia B, led to increased and sustained activity of clotting factor IX (FIX), according to one-year data from a Phase 2b clinical trial.

The therapy effectively prevented spontaneous bleeding episodes in patients with severe forms of the disease.

Trial findings were presented in a poster at the recent 62nd Annual Meeting of the American Society of Hematology. The abstract was titled, “One Year Data from a Phase 2b Trial of AMT-061 (AAV5-Padua hFIX variant), an Enhanced Vector for Gene Transfer in Adults with Severe or Moderate-Severe Hemophilia B.“

“These updated data show that a single administration of etranacogene dezaparvovec has been well tolerated now out 52 weeks and has increased FIX activity into the therapeutic range for people living with hemophilia B,” Steven Pipe, MD, professor of pediatrics and pathology and pediatric medical director of the hemophilia and coagulation disorders program at the University of Michigan and principal investigator in the HOPE-B trial, said in a press release.

“These data show a full year of meaningful clinical benefit for all three patients in the study, including durable levels of FIX activity with no bleeds, no requirement for infusions of FIX replacement therapy outside of surgery, and no need for immunosuppression,” Pipe said.

AMT-061 is an experimental gene therapy that uses the AAV5 viral delivery vector. The construct carries a genetically engineered, patented version of clotting factor IX (FIX), called the Padua variant (FIX-Padua), which leads to an approximately eight- to ninefold increase in FIX activity.

The investigational gene therapy was designated a breakthrough therapy by the U.S. Food and Drug Administration, and received priority medicines (PRIME) designation from the European Medicines Agency

The safety and effectiveness of AMT-061 are currently being investigated in three patients with severe hemophilia B (those whose FIX activity is 1% or less) participating in an open-label, single-dose Phase 2b trial (NCT03489291) currently underway in the U.S.

Each patient enrolled in the trial received a single intravenous (into-the-vein) infusion of AMT-061 at a dose of 2×10¹³ genome copies (gc)/kg and were followed for 52 weeks to assess the effects of treatment on FIX activity, bleed rates, and FIX replacement therapy usage. Study participants will continue to be monitored for the next five years to assess the safety of AMT-061.

One-year data from the three patients who received AMT-061 in the trial showed the therapy led to stable and sustained FIX activity. AMT-061 increased the activity of FIX to a mean of 41% of what would be considered normal in all participants, reaching up to 50% in the first patient dosed in the trial.

Moreover, in the year after the administration of AMT-061, none of the patients experienced any spontaneous bleeding episode or required prophylactic (preventive) treatment.

One of the patients gave a single infusion of FIX replacement to himself after experiencing back pain following hip surgery for a pre-existing and unrelated medical condition. Neither of the other two patients reported having used FIX replacement therapies during the study. “These data support the ongoing Phase 3 study,” the researchers wrote in the abstract.

The effectiveness of AMT-061 among patients with moderate and severe hemophilia B is being tested in the multicenter, open-label, single-arm Phase 3 HOPE-B trial (NCT03569891). The trial has already reached its  target enrollment and  is currently underway at several sites in the U.S. and Europe.

“We are very pleased with these latest results, and continue to believe that etranacogene dezaparvovec has the potential to be the first- and best-in-class gene therapy for patients with hemophilia B,” said Robert Gut, MD, PhD, chief medical officer of uniQure. “We remain focused on dosing all patients in our ongoing, fully enrolled HOPE-B pivotal trial, and expect to announce top-line data on our primary endpoint of Factor IX activity by the end of 2020.”

In addition to new data on AMT-061, uniQure presented updated data from its ongoing Phase 1/2 trial (NCT02396342) of AMT-060, the company’s first-generation gene therapy to treat hemophilia B.

All 10 patients enrolled in the study continue to experience long-term clinical benefits, including sustained increases in FIX activity, less FIX replacement therapy usage, and low bleeding rates, the company said.

Based on the six months of data collected during the fourth year of follow-up, the therapy continues to be safe and well-tolerated. No new serious adverse events or development of clotting factor inhibitors were reported since the trial’s latest update.

Six-month data gathered during the fourth year of follow-up revealed AMT-060 reduced the mean annual bleeding rate from four episodes a year to zero, corresponding to a reduction of 100%.

During the same period, treatment was found to decrease the use of FIX replacement therapies by 100% compared with the previous year.

“The Phase 1/2 study of AMT-060 continues to demonstrate notable long-term tolerability,” said Wolfgang Miesbach, MD, PhD, professor at University Hospital Frankfurt. “We have now demonstrated evidence of durable clinical benefits, including sustained FIX activity, improved disease phenotype [symptoms] and substantial reductions in spontaneous bleeds for up to four years following administration. These data have the potential to be very meaningful for hemophilia B patients.”

uniQure plans to use data from the Phase 1/2 study of AMT-060 to support a submission requesting marketing approval for AMT-061.