uniQure N.V. has announced positive two-year follow-up data from its Phase IIb study of etranacogene dezaparvovec, an investigational AAV5-based gene therapy for severe and moderately severe hemophilia B. The data, presented at the 62nd Annual Meeting of the American Society of Hematology (ASH), demonstrate sustained Factor IX (FIX) activity at therapeutic levels in treated patients.
Etranacogene Dezaparvovec Maintains Stable FIX Activity
The Phase IIb study, an open-label, single-dose trial, enrolled three patients with severe hemophilia B (FIX activity ≤1%). These patients received a single intravenous infusion of etranacogene dezaparvovec at a dose of 2x1013 gc/kg. The two-year follow-up data revealed that all three patients maintained FIX activity at therapeutic levels. The mean FIX activity at two years was 44.2% of normal, compared to 41% at 52 weeks. Individual FIX activity levels were 44.7%, 51.6%, and 36.3% of normal for the three patients, respectively.
Annette von Drygalski, M.D., PharmD, director of the Hemophilia and Thrombosis Treatment Center at the University of California San Diego, noted, "These clinical data show that a single administration of etranacogene dezaparvovec continues to be well tolerated by these patients through two years of follow-up with the potential to achieve durable increases of FIX activity within the normal range."
Reduced Bleeding and FIX Replacement Therapy
At two years post-dosing, two of the three participants remained free from bleeds and FIX replacement therapy. The third participant reported a single bleed and used a total of two FIX infusions (excluding surgery). All patients have remained free of prophylaxis since receiving etranacogene dezaparvovec.
Long-Term Data on AMT-060 Shows Sustained Benefits
uniQure also presented up to five-year follow-up data from the Phase I/II trial of AMT-060, its first-generation gene therapy for hemophilia B. The data showed long-term clinical benefits in all 10 patients, including sustained increases in FIX activity, reduced usage of FIX replacement therapy, and decreased bleeding frequency. No new treatment-related adverse events or development of inhibitors were reported during the study.
In the second dose cohort (2x1013 gc/kg), all five patients remained free of routine FIX replacement therapy at four-and-a-half years post-treatment. The mean annualized bleeding rate was zero compared to an average of 4 bleeds in the year prior to treatment, representing a 100% reduction. FIX replacement therapy usage also declined to zero compared to 354,800 IU in the year prior to treatment, also a 100% reduction. Mean FIX activity over 4.5 years was 7.4% in the higher dose cohort.
Regulatory Plans
Ricardo Dolmetsch, president of research and development at uniQure, stated, "These data will be included in regulatory submissions to the FDA and EMA, which we anticipate will begin in the second half of 2021, along with FIX activity and bleeding rates from the ongoing HOPE-B Phase III pivotal trial."
About Etranacogene Dezaparvovec
Etranacogene dezaparvovec consists of an AAV5 viral vector carrying a gene cassette with the patent-protected Padua variant of Factor IX (FIX-Padua). It has been granted Breakthrough Therapy Designation by the FDA and access to the PRIME regulatory initiative by the EMA. uniQure and CSL Behring have a licensing agreement granting CSL Behring exclusive global rights to etranacogene dezaparvovec.
