Last updated March 30, 2022, by Marta Figueiredo, PhD
✅ Fact-checked by Joana Carvalho, PhD
EtranaDez (etranacogene dezaparvovec; formerly called AMT-061) is an experimental gene therapy that uniQure is developing to treat hemophilia B. If approved, the therapy will be marketed globally by CSL Behring, which closed a commercialization and licensing agreement with uniQure in May 2021.
The European Medicines Agency began an accelerated review of EtranaDez for possible approval as a first gene therapy for hemophilia B in March 2022, with a decision likely by early fall. uniQure and CSL Behring expect to soon file a similar approval request with the U.S. Food and Drug Administration (FDA).
How does EtranaDez work?
Hemophilia B is caused by mutations in the F9 gene, which provides the instructions to make clotting factor IX (FIX), a protein required for normal blood clotting. People with hemophilia B have either low levels of FIX or an abnormal version of the protein, both of which impair the clotting process and result in a bleeding disorder.
EtranaDez uses a modified and harmless adeno-associated virus 5 (AAV5) to deliver a highly functional copy of the F9 gene, called FIX-Padua, to patients’ liver cells, the body’s main producers of clotting factors. The FIX-Padua gene version was shown to result in FIX clotting activity that’s five to eight times greater than the activity normally associated with the F9 gene. As such, the therapy — given as a one-time infusion directly into the bloodstream — is expected to increase FIX levels, helping to prevent and control bleeds for long periods of time.
EtranaDez in clinical trials
A Phase 2b trial (NCT03489291) is assessing the safety and effectiveness of a single dose of EtranaDez (as AMT-061) in three men with severe hemophilia B living in the U.S. Two-year data showed the therapy was generally safe and led to a stable and sustained FIX activity — with levels reaching up to more than 50% of what would be considered normal — in all three men.
EtranaDez’s use also prevented the occurrence of spontaneous bleeds and the need for FIX replacement therapy in two of the three patients, as well as the need for prophylaxis, or preventive therapy, in all these men. Participants are continuing to be monitored for five years, with the trial expected to conclude in September 2023.
An open-label Phase 3 study (NCT03569891), called HOPE-B, is evaluating EtranaDez’s five-year safety and effectiveness in 54 men with moderate-to-severe hemophilia B in the U.S. and in Europe. HOPE-B is the largest trial to date of an experimental gene therapy for hemophilia B, uniQure reported.
Top-line, six-month results showed that AMT-061 significantly increased FIX activity, reaching a mean of 37.2% of normal levels and meeting the trial’s main goal. The therapy was also found to strongly reduce bleeds and the need for preventive treatment.
One-year data from HOPE-B demonstrated that EtranaDez had sustained and durable effects, with patients achieving a mean of 41.5% of normal FIX activity levels and their annualized rate of bleeds requiring treatment dropping by 80% or more. All but two patients (96.3%) were able to discontinue routine preventive treatment and remain prophylaxis-free, and the use of FIX replacement therapies also fell by 96%.
Data at 1.5 years post-treatment also showed the therapy significantly increased FIX activity, reaching a mean of 36.9% of normal. This was associated with a 64% reduction in bleeding rates — from more than four bleeds per year to less than two, on average — and a 97% drop in yearly usage of FIX replacement therapy.
Nearly all participants (98%) given a full dose of EtranaDez also stopped using prophylaxis after 1.5 years.
Notably, these benefits were seen regardless of pre-existing antibodies against the therapy’s viral carrier, AAV5 — which can limit the therapy’s efficacy — suggesting that nearly all hemophilia B patients may benefit from EtranaDez.
The gene therapy was also found to be generally safe, with no treatment-related serious adverse events and no reported development of antibodies against the delivered FIX.
HOPE-B is expected to conclude in March 2025.
EtranaDez’s clinical program, including the Phase 2b and the Phase 3 HOPE-B trials, was placed on hold by the FDA in December 2020 after a HOPE-B participant developed hepatocellular carcinoma, a type of liver cancer. After an independent investigation showed it very unlikely that AMT-061 contributed to this cancer’s development, the FDA lifted the clinical hold in April 2021.
EtranaDez was designated a breakthrough therapy in the U.S. and a priority medicine (PRIME) in Europe, both meant to accelerate its development and regulatory review.
uniQure holds patents on the technology used to create EtranaDez in the U.S. and in Canada.
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