AMT-061 (etranacogene dezaparvovec)

AMT-061 (etranacogene dezaparvovec) 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.

uniQure and CSL Behring expect to file a regulatory application to the U.S. Food and Drug Administration (FDA) in early 2022 seeking AMT-061’s approval for hemophilia B.

How does AMT-061 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, resulting in a bleeding disorder.

AMT-061 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’ cells. The FIX-Padua gene version was shown to result in FIX clotting activity eight times greater than that associated with the standard F9 gene. As such, the one-time therapy — administrated directly into the bloodstream — is expected to increase FIX levels, helping to prevent and control bleeds.

AMT-061 in clinical trials

A Phase 2b trial (NCT03489291) is assessing the safety and effectiveness of a single dose of 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.

AMT-061 also prevented the occurrence of spontaneous bleeds and the need for FIX replacement therapy in two of the three participants, as well as the need for prophylaxis, or preventive therapy, in all these patients. Participants will continue to be monitored for a total of five years, with the trial expected to conclude in September 2023.

An open-label Phase 3 study (NCT03569891), called HOPE-B, is evaluating AMT-061’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 of an experimental gene therapy for hemophilia B, according to uniQure.

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 AMT-061’s sustained and durable effects, with patients achieving a mean of 41.5% of normal FIX activity levels and seeing their annualized rate of bleeds requiring treatment drop by 80% or more. All but two patients (96.3%) were able to discontinue routine preventive treatment and remained prophylaxis-free, and the use of FIX replacement therapies also dropped by 96%.

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 AMT-061.

The 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.

If confirmed at 1.5 years post-dosing, these positive findings are expected to support uniQure and CSL Behring’s planned request to the FDA for AMT-061’s approval to treat hemophilia B.

HOPE-B is expected to finish by March 2025.

Other information

AMT-061’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 a comprehensive, independent investigation showed that it was very unlikely that AMT-061 contributed to this cancer’s development, the FDA lifted the clinical hold in April 2021.

AMT-061 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 AMT-061 in the U.S. and in Canada.


Last updated: June 25, 2021


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