UniQure’s hemophilia B gene therapy achieves 31% FIX activity

UniQure expects to start dosing patients with AMT-061 in a phase 3 trial in the first quarter of next year. (uniQure)

UniQure has posted eagerly-anticipated data on the modified hemophilia B gene therapy it plans to take into phase 3. The FIX-Padua variant therapy achieved factor IX (FIX) activity levels of 23% to 37%, suggesting it is several times more effective than the version uniQure tested in earlier-phase trials.

Throughout development of its earlier, wild-type FIX gene therapy AMT-060, uniQure suffered as a result of unfavorable comparisons to Spark Therapeutics’ rival FIX Padua candidate SPK-9001. While the high dose of AMT-060 triggered FIX activity of 3% to 12.7%, the latest version of Pfizer-partnered SPK-9001 sent levels up to between 38.1% and 54.5%. A patient who received a version of SPK-9001 made under a previous process achieved FIX activity of 76.8%.

UniQure responded to the unfavorable comparisons by acquiring patents from Paolo Simioni and dropping AMT-060 in favor of FIX-Padua variant gene therapy AMT-061. Parallel to preparations for the AMT-061 phase 3, uniQure gave the new therapy to three patients in a dose-confirmation trial.

The Dutch biotech now has data on those patients. Across the three patients, six-week FIX activity came in at 31% of normal, far higher than was achieved by the wild-type AMT-060. There was some patient-to-patient variation, but the lowest level of FIX activity as of the cutoff was the 23% recorded by one person at eight weeks. Activity at cut off in the other two people was 37% and 30%.

UniQure is yet to present a detailed look at FIX levels over time but stated that the patients all had “increasing and sustained” activity. No patients “experienced a material loss of FIX activity," reported bleeding events or needed FIX infusions. The long-term efficacy of AMT-061 remains unknown, but uniQure thinks the sustained FIX activity in patients who received AMT-060 is a good omen. 

On the safety front, one patient experienced “a mild, asymptomatic increase in liver enzyme levels, which resolved quickly without any additional treatment,” uniQure said. Asymptomatic increases in liver enzymes were also seen in some patients who received AMT-060.

The two patients who achieved 23% and 30% levels of FIX activity—at eight and six weeks, respectively—had pre-existing neutralizing antibodies to an AAV vector that prevented their participation in a clinical trial of a different gene therapy. UniQure is using an AAV5 vector. Spark’s SPK-9001 and Shire and Baxalta’s now-abandoned BAX 335 use AAV8. 

UniQure is set to submit data on the three patients to U.S. and European regulators by the end of the year. If everything goes to plan, uniQure expects to start dosing patients with AMT-061 in a phase 3 trial in the first quarter of next year. Pfizer started a phase 3 lead-in study of SPK-9001 in July.