Hemophilia B: The Next Target for Gene Therapy?

Treatment with a single dose of AMT-061, an investigational gene therapy, led to increased factor IX (FIX) activity and reduced spontaneous bleeding episodes for patients with moderate to severe hemophilia B, according to results from a small phase IIb trial presented at the 2019 Congress of the International Society on Thrombosis and Haemostasis.

Although there were data from only three participants at the time of presentation, lead author Adam Giermasz, MD, PhD, director of the Hemophilia Treatment Center at University of California, Davis, noted that AMT-061 produced “clinically meaningful FIX activity.”

AMT-061 uses an adeno-associated virus serotype 5 (AAV5) vector containing a codon-optimized Padua variant human FIX gene with liver-specific promoter, the study authors explained.

The phase IIb, open-label, multicenter trial enrolled men with moderate to severe hemophilia B who required FIX prophylaxis. Patients were excluded if they had active hepatitis or uncontrolled HIV. All three participants had low titers to neutralizing antibodies. Two of the patients were HIV-positive and all three had been exposed to hepatitis C.

Participants received a single dose of AMT-061 at baseline and were monitored for immediate adverse events (AEs) at the trial site for 24 hours. The study’s primary endpoint was FIX activity levels of ≥5% after six weeks, and the investigators will continue to monitor patients for five years.

Researchers observed that FIX activity increased rapidly following treatment administration and the three patients reached an average FIX activity of 31% at week 6. Activity continued to increase during follow-up, reaching 38% at week 12 post-treatment.

“At 36 weeks, the mean FIX activity is 45%,” stated Dr. Giermasz during his presentation.

During the approximately nine-month follow-up, the number of spontaneous bleeds decreased to zero for all patients; prior to treatment, patients experienced between one and four spontaneous bleeds.

Dr. Giermasz also reported that that “there were no bleeds post-treatment and no requirement for FIX replacement” among the three participants. Alanine aminotransferase levels did not rise above normal limits after dosing for all participants, the researchers added. However, one participant experienced two mild AEs (headache and elevated C-reactive protein).

These findings are limited by the small patient population and the short duration of follow-up.

A phase III trial is ongoing, Dr. Giermasz noted. “The first patient was already enrolled in early 2019. Expected enrollment will be up to 55 participants, and there will be no exclusion of those who have pre-existing, neutralizing antibodies to AAV5,” he said.

The authors report relationships with uniQure, the manufacturer of AMT-061.


Giermasz A, Von Drygalski A, Castaman G, et al. AMT-061 (AAV5-Padua hFIX variant) an enhanced vector for gene transfer in adults with severe or moderate-severe hemophilia B: follow-up to 9 months in a phase 2b trial. Abstract OC 01.1. Presented at the International Society of Thrombosis and Haemostasis 2019 Congress, July 6, 2019; Melbourne, Australia.