uniqure delivers POC for hemophilia B gene therapy

AMT-061, an AAV5 vector, expresses a gene cassette with the Padua variant of Factor IX, which lacks in hemophilia B patients. According to uniqure, spontaneous bleeds decrease substantially when factor IX activity is above 12% of normal. Factor IX replacement therapy could be significantly reduced at that factor IX level.

All three patients with severe hemophilia B, enrolled in an open-label Phase IIb study of AMT-061 showed a factor IX activity of at least 25% above normal 12 weeks after administration of a single dose though they showed low levels of pre-existing antibodies to AAV5 before administration. The first patient achieved factor IX activity of 48% of normal at 16 weeks after administration. Factor IX activity in the second patient was 25% of normal at 14 weeks after administration, and the third patient achieved factor IX activity of 51% of normal at 12 weeks after administration. Reported factor IX activity was measured using an activated partial thromboplastin time (aPTT) assay performed at a central laboratory. Patients in the Phase IIb study will be followed for 52 weeks to assess factor IX activity, bleeding rates and usage of factor IX replacement therapy, and will be monitored for five years to evaluate the safety of AMT-061.

The study demonstrates AMT-061 has the potential to increase FIX activity into the normal range and continues to be very well tolerated, with no serious adverse events reported and no patients requiring any immunosuppression therapy, said Robert Gut, chief medical officer of uniQure. uniQure said it will complete enrollment of an ongoing pivotal Phase III study by the end of the year. AMT-061 has been granted FDA breakthrough and EMA PRIME status.

The pivotal, Phase III HOPE-B trial is a multi-center, open-label, single-arm study to evaluate the safety and efficacy of AMT-061. Approximately 50 adult patients with moderately to severe hemophilia B will be enrolled in a six-month observational period during which time they will continue to use their current standard of care to establish a baseline control. After the six-month lead-in period, patients will receive a single intravenous administration of AMT-061. According to uniqure, dosing of patients in the HOPE-B pivotal trial is underway.  The primary endpoint of the study will be based on the FIX activity level achieved following the administration of AMT-061, and the secondary endpoints will measure annualized FIX replacement therapy usage, annualized bleed rates and safety.

Fidanacogene elaparvovec from Spark Therapeutics Inc./Pfizer Inc. is another hemophilia B gene therapy in Phase III testing.