AMT-060 for hemophilia B

Last updated Feb. 6, 2024, by Margarida Maia, PhD
Fact-checked by Inês Martins, PhD

What is AMT-060 for hemophilia?

AMT-060 was a first-generation gene therapy for hemophilia B that was tested in clinical trials as a potential treatment for reducing the risk of bleeding episodes in patients.

The experimental medication was developed by uniQure, to be given as a one-time intravenous or into-the-vein infusion. However, the company decided to switch its development in 2017 for its successor, AMT-061. That gene therapy ultimately was approved as Hemgenix (etranacogene dezaparvovec) in 2022.

Therapy snapshot

How does AMT-060 work in hemophilia?

Hemophilia B is marked by little to no activity of a blood-clotting protein called factor IX (FIX), owing to mutations in the F9 gene that carries the instructions for making this protein. When the FIX protein is missing or abnormal as a result of such mutations, the blood cannot clot properly. Thus, people with this form of hemophilia tend to experience heavy bleeding episodes that are difficult to manage.

AMT-060 was a gene therapy designed to deliver a working copy of the F9 gene to liver cells, which produce most clotting factors in the body. The gene in this therapy was optimized to boost protein production in cells, but the resulting FIX protein had the exact same sequence as that found in healthy people.

The F9 gene was packaged inside a viral vector called adeno-associated virus 5, or AAV5, which does not cause disease in humans. When the vector unloaded its package into liver cells, the cells could then use the gene’s instructions to produce FIX on their own. This was expected to increase FIX levels in the blood, thereby helping to control bleeding episodes.

While this gene therapy did in fact increase FIX activity, it benefits were not significant, and no patients achieved normal activity levels of the clotting factor. Thus, uniQure developed another version of the F9 gene that differed from the one used in AMT-060.

While these versions differed by only two nucleotides — the DNA’s building blocks — the newer formulation made a FIX protein with a much greater clotting activity.

This was the version used in Hemgenix. Its much greater clotting activity with similar FIX levels may have been the grounds for transitioning the clinical development of AMT-060 to Hemgenix.

How was AMT-060 administered in hemophilia?

The only clinical trial that tested AMT-060 in hemophilia B patients administered it as a single intravenous infusion, at a dose of 5 trillion or 20 trillion genome copies per kilogram of body weight (gc/kg).

AMT-060 in hemophilia clinical trials

AMT-060 was tested in an open-label Phase 1/2 clinical trial (NCT02396342) that involved 10 adult men, ages 33 to 72. All had severe or moderately severe hemophilia B, meaning their FIX activity levels were no greater than 2% of normal.

The participants had previously received FIX infusions as standard replacement therapy for at least 150 days. In the trial, five patients received AMT-060 as a one-time intravenous infusion at a dose of 5 trillion gc/kg, and the other five were given a 20 trillion dose. All were then followed for five years.

At five years after receiving the gene therapy, patients in the lower dose group had achieved a mean FIX activity level of 5.2% of normal, while those given the higher dose reached an average of 7.2% of normal.

The annualized bleeding rate, a measure of the number of bleeding episodes per year, was 6.5 in the final year of observation for those given the 5 trillion dose — a 55% reduction compared with the year before treatment. That rate was zero for patients who received the 20 trillion dose, a 100% reduction from before treatment.

Consistent with the marked reduction in bleeding episodes, the use of the FIX replacement therapy in the last year of follow-up was reduced by more than 99% in the highest dose group. Among the nine patients receiving prophylaxis or preventive therapy at study’s start, eight had stopped using it after four years, and remained free of prophylaxis after five years.

None of the patients developed inhibitors, or neutralizing antibodies, against FIX nor a sustained immune response against its viral vector. Three patients experienced a temporary elevation in liver enzymes, a sign of liver damage.

After completing the five years of follow-up in the Phase 1/2 trial, nine patients opted to enroll in a long-term extension study (NCT05360706) designed to continue to test the safety and efficacy of AMT-060 for up to 10 years following infusion. This study is expected to wrap up in May 2026.

Common side effects of AMT-060

The most common side effect reported with AMT-060 during clinical testing was a transient, mild elevation of liver enzymes.

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