New Medicines

Severe and moderately severe haemophilia B


New molecular entity
CSL Behring

Development and Regulatory status

Phase III Clinical Trials
Pre-registration (Filed)
Pre-registration (Filed)
May 22Biologics License Application (BLA) for etranacogene dezaparvovec accepted by the US FDA for priority review. [21]
Mar 22EMA accepts MAA for haemophilia B under its accelerated assessment procedure [20].
Dec 21EMA HMP grants accelerated assessment for etranacogene (potentially reducing the review timeline from 210 days to 150 days once the MAA is filed and validated). EU filing is planned for H1 22 [19].
Oct 21Top-line data from Hope-B study expected by end of 2021. A BLA will be submitted by CSL Behring to the FDA in the H1 2022. uniQure anticipates completing validation of its commercial manufacturing process before end 2021 [17].
Apr 21FDA removes the clinical hold on the HOPE-B pivotal trial of AMT-061 after determining the company had satisfactorily addressed all issues related to a single patient diagnosed with hepatocellular carcinoma. uniQURE plans to announce top-line 52-week data from the HOPE-B pivotal trial later this quarter [14].
Dec 20FDA have placed development on clinical hold due to a patient developing liver cancer. This may not be related to the gene therapy, as this particular pt was high risk given their long history of hepatitis C, hepatitis B virus, findings of NASH disease and advanced age. The FDA and company plan to conduct a thorough investigation which expects to be completed in early 2021. The hold is not expected to affect the pivotal trial results.[12]
Nov 20uniQure intends to request pre-BLA meeting with the US FDA in Q1 21 [9].
Jun 20uniQure and CSL Behring enter into a licensing agreement providing CSL Behring with exclusive global rights to etranacogene dezaparvovec. This licensing agreement is subject to antitrust regulatory review in the US, Australia and the UK that is currently ongoing [9].
Apr 20UniQure announces it has achieved targeted dosing of 54 patients in the HOPE-B pivotal trial and, despite COVID-19, remains on track to provide 26-weeks of data for all patients in the trial before end of 2020 [7].
Mar 20UniQure announces it intends to file in the US in 2021 [6].
Mar 18Granted orphan drug status in EU [5].
Oct 17Company announces that the US FDA has agreed to include etranacogene dezaparvovec under the existing Breakthrough Therapy designation and Investigational New Drug (IND) for AMT 060. Additionally, the EMA has agreed that AMT 061 will be included under the current PRIME designation [4].


An in vivo gene therapy, given as a single dose, that uses adeno-associated virus 5 (AAV5) vector to deliver the highly functional Padua variant of the FIX gene to liver cells, where it stimulates production of FIX that is 8 times more active than normal
Haemophilia B has a prevalence of around 1 in 30,000 live births (around 20% incidence of haemophilia A) and affected males have a deficiency of Factor IX clotting factor. Severe disease occurs with a factor IX level below 1% of the reference and accounts for about 50% of cases [2].
Severe and moderately severe haemophilia B
Intravenous infusion

Further information


Trial or other data

Dec 21CSL Behring and uniQure announce that etranacogene achieved the pre-specified primary endpoint of non-inferiority in annualized bleeding rate (ABR) 18-months following administration compared to baseline Factor IX (FIX) prophylactic therapy in PIII HOPE-B gene therapy trial. The study also successfully achieved a secondary endpoint demonstrating statistical superiority in reduction of ABR compared to baseline FIX prophylactic therapy [18]
Sep 21PIII HOPE-B study completes collection of primary outcome data [16].
Mar 21Collection of primary outcome data due to complete this month in the PIII HOPE-B study [15].
Dec 20Long-term follow-up data (36 weeks) is available from a PIIb study (NCT03489291). Results in patients with severe or moderately severe haemophilia B showed that all three enrolled patients at week 52, experienced increasing and sustained factor IX (FIX) levels, after a single intravenous infusion of 2x1013 vc/kg of etranacogene dezaparvovec with two of the three patients achieving FIX activity in the normal range. Mean FIX activity increased to 31% 6-weeks after treatment and to 41% at 52-weeks (individual participant levels were 50%, 31% and 41%). Mean FIX activity for the three patients at 36 weeks after administration was 45% of normal, with the first patient achieving FIX activity of 54% of normal, the second patient achieving FIX activity of 30% of normal and the third patient achieving FIX activity of 51% of normal. The second and third patients had previously screen-failed and were excluded from another gene therapy study due to pre-existing neutralizing antibodies to a different AAV vector [10].
Nov 20CSL Behring and uniQure announce top-line data from pivotal PIII HOPE-B trial (n=54). Etranacogene dezaparvovec boosted Factor IX levels from below 2% or normal to 37% at 26 weeks meeting the trial primary outcome. In a 26 week follow up period, 72% of patients reported no bleeding events, while 15 patients reported a total of 21 bleeds [8].
Dec 19NCT03569891-UK trial sites Bristol, Cambridge, Barts, Southampton [3]
Feb 19PIII HOPE-B trial starts - multi-center, open-label, single-arm study to evaluate safety and efficacy of AMT-061. Approx 50 adult hemophilia B patients (severe or moderately severe) will be enrolled in a six-month observational period using their current standard of care to establish a baseline control. After the six-month lead-in period they will receive a single intravenous administration of AMT-061 gene therapy [1]. The primary endpoint of the study will be based on the Factor IX activity level achieved following the administration of AMT-061 [1].

Evidence based evaluations