UniQure
UniQure
UniQure has two gene therapy products in development for haemophilia B. AMT-060 which uses a wild type gene and etranacogene dezaparvovec (AAV5-hFIXco-Padua, AMT-061), which uses the Padua variant gene [1, 2]. UniQure has agreed a distribution arrangement with CSL Behring for etranacogene dezaparvovec.
| AMT-060 | AMT-061 |
| Outcomes after one year have formally been published in full [3] | A Phase I/II study evaluated the dose to be used in Phase III HOPE-B trial; three participants received a dose of 2×1013 vg/kg |
| Outcomes after 3 and 4 years were published in abstract form in 2019 [4] | In the first participant, FIX level was 37% after ten weeks; in the second it was 23% after eight weeks; in the third, it was 30% after six weeks. The second and third patients had pre-existing neutralising antibodies to a different AAV vector |
| In patients followed up for 4 years, mean yearly factor IX activity 4.4% after the first year, 6.8% after year 2, 7.3% after year 3 and 6/0% in year 4 | Mean FIX activity after six weeks was 31% and continues to increase |
| In those followed up for 3 years, it was 7.1%, 8.4% and 7.9% | So far, no participant have required FIX infusion; no bleeding events have been reported, and no one has required immunosuppressive therapy |
| Eight patients had discontinued prophylaxis | A mild, asymptomatic and transient increase in liver enzyme levels occurred in one participant; this resolved without treatment |
| In the 4-year cohort, mean annualised bleed rate was 1,7, a reduction of 88% and a fall in factor IX use of 93% | According to UniQure, all three patients had stabilized and sustained factor IX activity at therapeutic levels after 52 weeks of follow-up [5] |
| In the 3-year cohort, it was 0.7, a reduction of 83% and a fall in factor IX use of 96% | HOPE-B had recruited 54 patients by March 2020 and top-line results are expected by the end of the year; the primary endpoint is factor IX activity after 26 weeks |
| Three patients developed transient mild increases in alanine aminotransferase; one patient had joint swelling after exercise in the last 12 months of follow up |
References
- uniQure Announces Long-Term Clinical Data from Ongoing Phase I/II Trial of AMT-060 and Confirms Dose for AMT-061 Pivotal Study in Hemophilia B.
- uniQure Announces Initial Topline Data from Dose-Confirmation Study of AMT-061 in Patients with Hemophilia B
- Miesbach W, Meijer K, Coppens M, et al. Gene therapy with adeno-associated virus vector 5-human factor IX in adults with hemophilia B. Blood 2018;131:1022-1031.
- Miesbach W, Meijer K, Coppens M et al. Stable FIX expression and durable reductions in bleeding and factor IX consumption for up to 4 years following AMT-060 gene therapy in adults with severe or moderate-severe hemophilia B. Blood (2019) 134 (Supplement 1): 2059.
- uniQure Announces Achievement of Target Patient Dosing in HOPE-B Pivotal Trial of AMT-061 (Etranacogene Dezaparvovec) in Hemophilia B. 26 March 2020.